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Abstract Objective The aim of this study was to establish an ensemble learning model based on clinicopathological parameter and ultrasound radomics for assessing the risk of lateral cervical lymph node with short diameter less than 8 mm (small lymph nodes were used instead) metastasis in patients with papillary thyroid cancer (PTC), thereby guiding the selection of surgical methods. Methods This retrospective analysis was conducted on 454 patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy and lateral neck lymph node dissection or lymph node intraoperative frozen section biopsy at the First Hospital of China Medical University between January 2015 and April 2022. In a ratio of 8:2, 362(80%) patients were assigned to the training set and 92(20%) patients were assigned to the test set. Clinical pathological features and radomics features related to ultrasound imaging were extracted, followed by feature selection using recursive feature elimination (RFE). Based on distinct feature sets, we constructed ensemble learning models comprising random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), gradient boosting decision tree (GBDT), and light gradient boosting machine (Lightgbm) to develop clinical models, radiomics models, and clinical-radiomic models. Through the comparison of performance metrics such as area under curve (AUC), accuracy (ACC), specificity (SPE), precision (PRE), recall rate, F1 score, mean squared error (MSE) etc., we identified the optimal model and visualized its results using shapley additive exPlanations (SHAP). Results In this study, a total of 454 patients were included, among whom 342 PTC patients had small lymph node metastasis in the lateral neck region, while 112 did not have any metastasis. A total of 1035 features were initially considered for inclusion in this study, which were then narrowed down to 10 clinical features, 8 radiomics features, and 17 combined clinical-omics features. Based on these three feature sets, a total of fifteen ensemble learning models were established. In the test set, RF model in the clinical model is outperforms other models (AUC = 0.72, F1 = 0.75, Jaccard = 0.60 and Recall = 0.84), while CatBoost model in the radiomics model is superior to other models (AUC = 0.91, BA = 0.83 and SPE = 0.76). Among the clinical-radiomic models, Catboost exhibits optimal performance (AUC = 0.93, ACC = 0.88, BA = 0.87, F1 = 0.91, SPE = 0.83, PRE = 0.88, Jaccard = 0.83 and Recall = 0.92). Using the SHAP algorithm to visualize the operation process of the clinical-omics CatBoost model, we found that clinical omics features such as central lymph node metastasis (CLNM), Origin_Shape_Sphericity (o_shap_sphericity), LoG-sigma3_first order_ Skewness (log-3_fo_skewness), wavelet-HH_first order_Skewness (w-HH_fo_skewness) and wavelet-HH_first order_Skewness (sqr_gldm_DNUN) had the greatest impact on predicting the presence of lateral cervical small lymph node metastasis in PTC patients. Conclusions (1) In this study, among the ensemble learning models established based on clinicopathological features and radiomics features for predicting PTC lateral small lymph node metastasis, the clinical-radiomic CatBoost model has the best performance. (2) SHAP can visualize how the clinical and radiomics features affect the results and realize the interpretation of the model. (3) The combined CatBoost model can improve the diagnostic accuracy of suspicious lymph nodes with short diameter

Abstract Background The neurovascular theory is thought to be one of the main pathological mechanisms of migraine. Locus coeruleus (LC) is a major node in the neurovascular pathway. Exploring the functional network characteristics of LC in migraine without aura (MwoA) patients can help us gain insight into the underlying neural mechanisms in MwoA patients. Methods In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) and a functional connectivity (FC) approach to explore the functional characteristics of LC in MwoA patients. 17 healthy controls (HCs) and 28 MwoA patients were included in the study. FC was calculated based on rsfMRI data collected by a 3T MRI scanner. General linear model were used to compare whether there were differences in LC brain networks between the two groups. We also utilized logistic regression to explore the role of LC functional networks in the clinical diagnosis of MwoA. Results After general linear analysis, MwoA patients displayed increased FC from right LC to the left lingual and calcarine sulcus, as well as to the right frontal medial gyrus/orbit part, when compared with HCs. The results of the logistic regression showed that the LC FC signals were 81% accurate in distinguishing MwoA from the HCs. Conclusion Our results demonstrated that patients with MwoA exhibited significant LC FC differences in the brain areas associated with visual and cognitive function. Understanding the changes in the LC brain network in MwoA patients can provide us with new ideas to understand the pathological mechanisms of MwoA.

Abstract Background F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). Methods This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. Results The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. Conclusions A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Abstract The rapid growth of offshore wind farms (OWFs) is driven by concerns for energy security and climate change mitigation. However, their impact on marine environments remains poorly understood due to limited research. This study analyzes the effects of an OWF along China's Jiangsu Coast on seawater quality using data from different development phases. Results show the major pollutants were different across phases. Heavy metal pollution reached alert levels during construction compared to the safe levels observed in the pre-construction and operational phases, mainly due to increases in Pb, Cd, and Hg concentrations. Eutrophication was mild throughout all periods but exhibited a continuous decrease, primarily attributed to reductions in PH and COD concentrations. As a result, the comprehensive pollution level during construction was increased, but it was improved to a clean level during the operational phase. Besides, significant variations were observed in the spatial distribution patterns of major pollutant indices across different scenarios. These changes may stem from a combination effect of land-based pollution, aquaculture, OWF-induced disturbances to atmosphere and hydrodynamics, OWF-related drain and leakage contamination, and marine management policies. Understanding these effects informs OWF optimization, rational wind resource utilization, and marine ecology protection.

BackgroundMultimorbidity imposes a heavy burden on individuals, families, and society. There are relatively few studies exploring patterns of multimorbidity among middle-aged adults in China. ObjectiveTo explore the current status of multimorbidity, associated risk factors, and multimorbidity patterns among adults aged 45-64 years in China, so as to provide a scientific basis to prevent and control multimorbidity in China. MethodsA total of 5494 adults aged 45-64 years from the Chinese Health and Nutrition Survey (CHNS) in 2018 were selected. Of these, 2494 (45.39%) were men and 3000 (54.61%) were women. The nine diseases included were hypertension, diabetes, dyslipidaemia, obesity, mild cognitive impairment (MCI), myocardial infarction, stroke, asthma, and tumor. The prevalence of each disease or multimorbidity was expressed as N (%). Comparisons of multimorbidity prevalence between different groups were performed using the χ2 test or Cochran-Armitage trend test. Association rule with the Apriori algorithm was used to explore the pattern of multimorbidity, with parameters set at a minimum conditional support of 3.00%, a minimum rule confidence of 50.00%, and a lift of >1.20. Logistic regression was used to evaluate the associations between selected risk factors and multimorbidity. ResultsIn 2018, 37.44% of participants reported multimorbidity in 15 provinces of China. The prevalence of diseases in descending order was dyslipidaemia (39.99%), hypertension (39.48%), obesity (16.42%), MCI (14.47%), diabetes (14.16%), tumor (1.09%), stroke (1.04%), myocardial infarction (0.71%), and asthma (0.64%). A total of seven multimorbidity patterns were identified in this group. Obesity paired with hypertension, and diabetes paired with dyslipidemia were the two major patterns of multimorbidity in the general population and age or sex subgroups. The multimorbidity patterns of different populations were concentrated in the combination of obesity, hypertension, diabetes, and dyslipidemia. The risk of multimorbidity was lower in females than in males (OR=0.85, 95%CI: 0.75, 0.97). The multimorbidity risk was 1.56 times higher in the 55-64 years group than in the 45-54 years group (OR=1.56, 95%CI: 1.40, 1.75). Drinking in the past year increased the risk of multimorbidity by 25% (OR=1.25, 95%CI: 1.08, 1.45) compared to no alcohol comsumption in the past year. High and medium levels of physical activity were associated with a decreased OR (high: OR=0.74, 95%CI: 0.65, 0.85; medium: OR=0.81, 95%CI: 0.70, 0.93) with low level of physical activity as reference. ConclusionIn 2018, there was a high prevalence rate of multimorbidity among middle-aged adults in China. The main multimorbidity patterns were obesity-hypertension and diabetes-dyslipidemia. Surveillance and interventions should be strengthened particularly for men, individuals with alcohol consumption or insufficient physical activity, and those with major multimorbidity patterns.

Valvular heart diseases (VHDs) have become one of the most prevalent heart diseases worldwide, and prosthetic valve replacement is one of the effective treatments. With the fast development of minimal invasive technology, transcatheter valves replacement has been exploring in recent years, such as transcatheter aortic valve replacement (TAVR) technology. In addition, basic research on prosthetic valves has begun to shift from traditional mechanical valves and biological valves to the development of polymeric heart valves. The polymeric heart valves (PHVs) have shown a bright future due to their advantages of longer durability, better biocompatibility and reduced cost. This review gives a brief history of the development of polymeric heart valves, provides a summary of the types of polymer materials suitable for heart leaflets and the emerging processing/preparation methods for polymeric heart valves in the basic research. Besides, we facilitate a deeper understanding of polymeric heart valve products that are currently in preclinical/clinical studies, also summary the limitations of the present researches as well as the future development trends. Hence, this review will provide a holistic understanding for researchers working in the field of prosthetic valves, and will offer ideas for the design and research of valves with better durability and biocompatibility.

Abstract Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.

Abstract Pediatric papillary thyroid carcinomas (PPTCs) exhibit high inter-tumor heterogeneity and currently lack widely adopted recurrence risk stratification criteria. Hence, we propose a machine learning-based objective method to individually predict their recurrence risk. We retrospectively collect and evaluate the clinical factors and proteomes of 83 pediatric benign (PB), 85 pediatric malignant (PM) and 66 adult malignant (AM) nodules, and quantify 10,426 proteins by mass spectrometry. We find 243 and 121 significantly dysregulated proteins from PM vs. PB and PM vs. AM, respectively. Function and pathway analyses show the enhanced activation of the inflammatory and immune system in PM patients compared with the others. Nineteen proteins are selected to predict recurrence using a machine learning model with an accuracy of 88.24%. Our study generates a protein-based personalized prognostic prediction model that can stratify PPTC patients into high- or low-recurrence risk groups, providing a reference for clinical decision-making and individualized treatment.

Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients’ gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.

ABSTRACTObjectives Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl−1/mIU∙l−1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD).Methods Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995–1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl−1/mIU∙l−1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening.Results In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19–1.86). In CONPASS, when compared to essential hypertension with ARR

Background: The prognosis of patients with hepatoblastoma has been unsatisfactory. This study analyzed the effects of different treatment methods on cancer-specific survival (CSS) in children with hepatoblastoma. Method: From 2000 to 2018, patients with hepatoblastoma were included in the Surveillance, Epidemiology, and End Results (SEER) database. CSS was estimated using the Kaplan–Meier method. Cox regression analysis assessed prognostic factors. The predictive models were validated using the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. Result: Of the 785 included patients, 730 (93.0 %) underwent chemotherapy, 516 (65.7 %) underwent liver tumour resection and 129 (16.4 %) underwent liver transplantation. Both chemotherapy and surgery could significantly improve the CSS rate (all p 0.05) had a similar prognosis. Multivariate analysis revealed that age (p = 0.003), race (p = 0.001), operative method (p

BackgroundThe anterior cingulate gyrus (ACG) is an important regulatory region for pain-related information. However, the ACG is composed of subregions with different functions. The mechanisms underlying the brain networks of different subregions of the ACG in patients with migraine without aura (MwoA) are currently unclear.MethodsIn the current study, resting-state functional magnetic resonance imaging (rsfMRI) and functional connectivity (FC) were used to investigate the functional characteristics of ACG subregions in MwoA patients. The study included 17 healthy volunteers and 28 MwoA patients. The FC calculation was based on rsfMRI data from a 3 T MRI scanner. The brain networks of the ACG subregions were compared using a general linear model to see if there were any differences between the two groups. Spearman correlation analysis was used to examine the correlation between FC values in abnormal brain regions and clinical variables.ResultsCompared with healthy subjects, MwoA patients showed decreased FC between left subgenual ACG and left middle cingulate gyrus and right middle temporal gyrus. Meanwhile, MwoA patients also showed increased FC between pregenual ACG and right angular gyrus and increased FC between right pregenual ACG and right superior occipital gyrus. The FC values between pregenual ACG and right superior occipital gyrus were significantly positively correlated with the visual analogue scale.ConclusionDisturbances of FC between ACG subregions and default model network and visual cortex may play a key role in neuropathological features, perception and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.

Background: Brucellosis is a zoonotic infectious disease. Neurobrucellosis occurs when Borrelia burgdorferi infects the nervous system and is a complication of brucellosis. Infection is a common post-cranioplasty complication, although co-infection with B. burgdorferi is rare. In this article, we report a case of neurobrucellosis caused by B. burgdorferi infection after cranioplasty in a female patient with traumatic brain injury and review the literature. Case Description: A 37-year-old woman with traumatic brain injury underwent emergency clot removal and decompression craniectomy. Three-dimensional titanium mesh cranioplasty was performed 4 years later. Unfortunately, only 1 year later, the skull repair material had to be removed because of a localized scalp infection in the area of the skull repair. Cranioplasty was performed 5 months later with polyetheretherketone material. The patient remained free of symptoms until July 27, 2022, when the patient was readmitted for a headache. The final diagnosis of neurobrucellosis was made after relevant examinations, tests, and subcutaneous puncture of aspirated pus for bacterial cultures and special genus tests. Following the standard protocol, the patient was treated effectively. Conclusion: Neurobrucellosis occurs after a patient contracts a neurological infection through contact with the excrement of an infected animal or ingestion of food from an infected or diseased animal. Any postoperative complications of specific infections can cause physical pain and a heavy financial burden on the patient because of the special and expensive materials used for cranial repair. Therefore, we recommend screening patients from areas at epidemiological risk for relevant diseases before undergoing cranioplasty.

Abstract Accumulating evidence has implicated impaired extracellular matrix (ECM) clearance as a key factor in fibrotic disease. Despite decades of research elucidating the effectors of ECM clearance, relatively little is understood regarding the upstream regulation of this process. Collagen is the most abundant constituent of normal and fibrotic ECM in mammalian tissues. Its catabolism occurs through extracellular proteolysis and cell-mediated uptake of collagen fragments for intracellular degradation. Given the paucity of information regarding the regulation of this latter process, here we execute unbiased genome-wide screens to understand the molecular underpinnings of cell-mediated collagen clearance. Using this approach, we discover a mechanism through which collagen biosynthesis is sensed by cells internally and directly regulates clearance of extracellular collagen. The sensing mechanism appears to be dependent on endoplasmic reticulum-resident protein SEL1L and occurs via a noncanonical function of this protein. This pathway functions as a homeostatic negative feedback loop that limits collagen accumulation in tissues. In human fibrotic lung disease, the induction of this collagen clearance pathway by collagen synthesis is impaired, thereby contributing to the pathological accumulation of collagen in lung tissue. Thus, we describe cell-autonomous, rheostatic collagen clearance as an important pathway of tissue homeostasis.

Abstract Background The stalk traits stalk diameter, stalk length, rind penetrometer resistance and dry matter content are important indicators for measuring lodging resistance. Results In this study, 377 inbred lines were used as the basic materials, and four stalk-related traits including stalk diameter, stalk length, rind penetrometer resistance and dry matter content of the third segment of maize, were investigated at the tasseling, grain filling, and maturity stages. 461,053 high-quality SNPs which were obtained by whole genome resequencing were used for genome-wide association study. As a result of mixed linear model analysis (P

Abstract The Proboscidea, which includes modern elephants, were once the largest terrestrial animals among extant species. They suffered mass extinction during the Ice Age. As a unique branch on the evolutionary tree, the Proboscidea are of great significance for the study of living animals. In this study, we generate chromosome-scale and haplotype-resolved genome assemblies for two extant Proboscidea species (Asian Elephant, Elephas maximus and African Savannah Elephant, Loxodonta africana) using Pacbio, Hi-C, and DNBSEQ technologies. The assembled genome sizes of the Asian and African Savannah Elephant are 3.38 Gb and 3.31 Gb, with scaffold N50 values of 130 Mb and 122 Mb, respectively. Using Hi-C technology ~97% of the scaffolds are anchored to 29 pseudochromosomes. Additionally, we identify ~9 Mb Y-linked sequences for each species. The high-quality genome assemblies in this study provide a valuable resource for future research on ecology, evolution, biology and conservation of Proboscidea species.

Background: Cyclin B2 (CCNB2) is associated with cell cycle progression, acting as a cell cycle checkpoint in progression of G2/M transition. In many cancer patients, it has been observed that overexpression of CCNB2 enhances tumor invasiveness and leads to adverse prognosis. However, the association of CCNB2 with the tumor microenvironment remains unclear. Therefore, it is necessary to clarify the associations of CCNB2 with the immune status and prognosis of breast carcinoma (BRCA). Methods: Gene expression and clinical data for BRCA were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, followed by association analyses of CCNB2 expression with prognosis, immune cell infiltration, and immune checkpoints. This study further performed drug sensitivity analysis and constructed a prognostic nomogram for CCNB2. Results: 3619 differentially expressed genes were identified in BRCA, including CCNB2 that emerged as a key gene in the network. High CCNB2 expression correlated with poor prognosis. Functional analysis demonstrated enrichment of CCNB2 co-expressed genes with the cell cycle, cancer progression, cell energy, and immune pathways. Microsatellite instability and tumor mutation burden analyses indicated CCNB2 as a candidate immunotherapy target. Tumor-infiltrating myeloid-derived suppressor cells, regulatory T cells, and T helper 2 cells were associated with CCNB2-related tumor progression and metastasis. CCNB2 expression positively correlated with immune checkpoints, indicating that high CCNB2 expression might facilitate tumor immune escape. Tumors with high CCNB2 expression showed sensitivity to phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin and cyclin-dependent kinase (CDK) 4/6 inhibitors, and the nomogram had good prognostic predictive ability for patients with BRCA. Conclusions: CCNB2 may play a crucial role in tumorigenesis and serve as an independent prognostic biomarker associated with tumor microenvironment, tumor immune infiltration and immunotherapy in BRCA.

Abstract The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals’ gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1‐palmitoyl‐2‐palmitoleoyl‐GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging‐related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

Excessive oxidation can lead to inflammation and affect health. Studies have shown that ursolic acid (UA) and gallic acid are widely employed in medicine and cosmetics owing to their obvious antioxidant and anti-inflammatory properties. In this study, a series of 16 novel UA hybrids tethered via 1,2,3-triazole to the modified gallate moieties were synthesized via CuAAC 1,3-cycloaddition reactions. In vitro, all derivatives were proved to be effective in antioxidation and anti-inflammation activities. Interestingly, compound 20 significantly inhibited the expression of pro-inflammatory cytokines including mRNA of inducible nitric oxide synthase (iNOS) (p

tRNA-derived small RNAs (tsRNAs) constitute a subgroup of small noncoding RNAs (ncRNAs) originating from tRNA molecules. Their rich content, evolutionary conservatism, high stability, and widespread existence makes them significant in disease research. These characteristics have positioned tsRNAs as key players in various physiological and pathological processes. tsRNA actively participates in regulating many cellular processes, such as cell death, proliferation, and metabolism. tsRNAs could be promising diagnostic markers for cardiovascular diseases (CVDs). tsRNAs have been identified in serums, suggesting their utility as early indicators for the diagnosis of CVDs. Moreover, the regulatory roles of tsRNAs in CVDs make them promising targets for therapeutic intervention. This review provides a succinct overview of the characteristics, classification, and regulatory functions of tsRNAs in the context of CVDs. By shedding light on the intricate roles of tsRNAs, this knowledge could pave the way for the development of innovative diagnostic tools and therapeutic strategies for CVDs.

With the serious aging population and lifestyle changes, chronic venous insufficiency accounts for approximately 25.95% of the population, which may lead to lower limb edema and leg heaviness, as well as severe infections of skin ulcers that can result in sepsis and necessitate amputation. Conservative treatment and other supportive measures can only slow the disease's progression but are unable to drastically reverse it; surgical interventions are rarely used due to the high risk of catastrophic postoperative consequences. As one of the most promising minimally invasive therapies, percutaneous prosthetic valve replacement has emerged in light of this situation, providing novel alternatives for patients with deep venous valve insufficiency. We reviewed the historical prosthetic venous valve designs, including their structure and materials, animal evaluation models, and assessment criteria. On the basis of the findings from in vitro tests, animal studies, and clinical trials, we summarized the major challenges and potential solutions for the development of advanced prosthetic venous valves.

Abstract Background Lateral lymph node metastasis (LLNM) is common in patients with papillary thyroid cancer (PTC), usually occurring after central lymph node metastasis (CLNM). However, some patients experience LLNM without first developing CLNM. This study aimed to identify the risk factors for developing LLNM without CLNM. Methods We retrospectively reviewed 421 patients diagnosed with PTC who underwent lobectomy or total thyroidectomy with central and ipsilateral lateral lymph node dissection. We collected clinicopathological data and used univariate and multivariate logistic regression analyses to determine the risk factors associated with LLNM without CLNM. Results The LLNM without CLNM frequency was 18.3% (77/421). Univariate analyses demonstrated that age over 55 years, primary tumor in the upper portion of the thyroid, the number of central lymph node (CLN) and LLNM, primary tumor size, and the summed size of multi‐foci tumors smaller than 1 cm were significantly associated with LLNM without CLNM (p

Abstract Background Individuals in the workplace are exposed to various environments, tasks, and schedules. Previous studies have indicated a link between occupational exposures and an increased risk of chronic kidney disease (CKD). However, the social conditions of the work environment may also be a crucial contributing factor to CKD. Furthermore, individuals may encounter multiple occupational-related risk factors simultaneously, underscoring the importance of investigating the joint risk of different working conditions on CKD. Methods A prospective analysis of 65,069 UK Biobank participants aged 40 to 69 years without CKD at baseline (2006–2010) was performed. A self-administered questionnaire assessed working conditions and a working conditions risk score were developed. Participants who answered “sometimes” or “often” exposure to occupational heat or occupational secondhand cigarette smoke; involved in shift work or heavy workloads (“usually” or “always”), were grouped as high-risk working conditions. Each working condition was scored as 1 if grouped as high-risk, and 0 if not. The working conditions risk score was equal to the sum of these four working conditions. Cox proportional hazard regression models were used to estimate the associations between working conditions and CKD incidence. Results The mean follow-up time was 6.7 years. After adjusting for demographic, lifestyle, and working time factors, the hazard ratios for the development of CKD for heavy workloads, shift work, occupational secondhand cigarette smoke exposure, and occupational heat exposure were 1.24 (95%CI = 1.03, 1.51), 1.33 (95%CI = 1.10, 1.62), 1.13 (95%CI = 1.01, 1.26), 1.11 (95%CI = 0.99, 1.24), respectively. The risk of CKD was found to be significantly associated with an increasing working conditions risk score. Individuals with a working conditions risk score of 4 had an 88.0% (95% CI = 1.05, 3.35) higher risk of developing CKD when compared to those with a working conditions risk score of 0. Conclusions Adverse working conditions, particularly when considered in combination, can significantly elevate the risk of chronic kidney disease (CKD). These results provide a reference for implementing measures to prevent CKD.

Abstract Purpose To construct a novel nomogram model that can predict DVT and avoid unnecessary examination. Methods Patients admitted to the hospital with pelvis/acetabular fractures were included between July 2014 and July 2018. The potential predictors associated with DVT were analyzed using Univariate and multivariable logistic regression analysis. The predictive nomogram was constructed and internally validated. Results 230 patients were finally enrolled. There were 149 individuals in the non-DVT group and 81 in the DVT group. Following analysis, we obtained the final nomogram model. The risk factors included age (OR, 1.037; 95% CI, 1.013–1.062; P = 0.002), body mass index (BMI) (OR, 1.253; 95% CI, 1.120–1.403; P 0.05). The decision curve analysis (DCA) and Clinical impact plot (CIC) demonstrated superior clinical use of the nomogram. Conclusions An easy-to-calculate nomogram model for predicting DVT in patients with pelvic-acetabular fractures were developed. It could help clinicians to reduce DVT and avoid unnecessary examinations.

High-precision positioning is a fundamental requirement for autonomous vehicles. However, the accuracy of single-sensor positioning technology can be compromised in complex scenarios due to inherent limitations. To address this issue, we propose an adaptive multi-sensor fusion localization method based on the error-state Kalman filter. By incorporating a tightly coupled laser inertial odometer that utilizes the Normal Distribution Transform (NDT), we constructed a multi-level fuzzy evaluation model for posture transformation states. This model assesses the reliability of Global Navigation Satellite System (GNSS) data and the laser inertial odometer when GNSS signals are disrupted, prioritizing data with higher reliability for posture updates. Real vehicle tests demonstrate that our proposed positioning method satisfactorily meets the positioning accuracy and robustness requirements for autonomous driving vehicles in complex environments.

The relationship between distinct dietary selenium intake and type 2 diabetes (T2D) is still a topic of uncertainty. This study examined the relationship between dietary selenium intake and T2D risk among middle-aged and older Chinese adults. Dietary selenium intake was assessed through three 24 h recalls, using data from the China Health and Nutrition Survey. To investigate the relationship and the potential dose–response pattern between selenium intake and the likelihood of developing T2D, we employed both the restricted cubic spline analysis and the Cox proportional hazards model as our analytical tools. A cohort of 5970 participants aged ≥ 50 years was followed for an average of 5.44 years. The results revealed a V-shaped correlation between selenium intake and T2D risk, with the lowest risk observed at approximately 45 µg/day. Below this level, the risk decreased with an increasing selenium intake, while the risk increased between 45 and 100 µg/day. No significant association was found beyond 100 µg/day. These findings suggest that both low and high selenium consumption may increase T2D risk, highlighting the importance of maintaining a balanced selenium intake for T2D prevention.

Background: Thyroid-associated ophthalmopathy (TAO) is an orbital disease closely related to thyroid disease with a long-lasting duration that can be blinding and disabling. Recently, structural and functional neuroimaging studies have been performed in TAO patients, but studies have reported inconsistent results. This quantitative meta-analysis was conducted to identify convergent patterns of abnormal brain function among different studies in TAO. Methods: We searched PubMed, EMBASE, Cochrane, and Web of Science, performed reference tracking, and retrieved 15 eligible studies. Peak coordinates were extracted from these studies and subsequently tested for convergence using activation likelihood estimation (ALE). Results: Compared to healthy subjects, resting-state brain activity in the whole brain of TAO patients was significantly increased in the left superior frontal gyrus (SFG) and decreased in the left cuneus/precuneus. Functional decoding analysis of the BrainMap database revealed that these regions are predominantly associated with cognitive and emotional impairment. In this study, task-related meta-analytic connectivity modeling (MACM) analysis was used to describe the connectivity and function of the two seed regions. Significant coactivation of these regions was found primarily in the bilateral superior parietal lobule, medial frontal gyrus, left fusiform gyrus, left cingulate gyrus, supplementary motor area and thalamus. Conclusion: Our findings underscore the role of the SFG and the cuneus/precuneus in the pathophysiology of TAO, highlighting the crucial impact of working memory deficits.

BRAF is a key member in the MAPK signaling pathway essential for cell growth, proliferation, and differentiation. Mutant BRAF is often the underlying cause of various types of cancer and mutant RAS, the upstream regulator of BRAF, is a driver of up to one-third of all cancers. BRAF interacts with RAS and undergoes a conformational change from an inactive, autoinhibited monomer to an active dimer, which propagates downstream signaling. Because of BRAF’s complex regulation mechanism, the exact order and magnitude of its activation steps have yet to be confirmed experimentally. By studying the inter- and intramolecular interactions of BRAF, we unveil the domain-specific and isoform-specific details of BRAF regulation through pulldown assays, open surface plasmon resonance (OpenSPR), and hydrogen-deuterium exchange mass spectrometry (HDX-MS). We demonstrate that the BRAF specific region (BSR) and cysteine rich domain (CRD) play a crucial role in regulating the activation of BRAF in a RAS isoform-specific manner. Moreover, we quantified the binding affinities between BRAF N-terminal and kinase domains (KD) to reveal their individual roles in autoinhibition. Our findings also indicate that oncogenic BRAF-KDD594G mutant has a lower affinity for the N-terminal domains, implicating that pathogenic BRAF acts through decreased propensity for autoinhibition. Collectively, our study provides valuable insight into the activation mechanism of BRAF kinase to guide the development of new therapeutic strategies for cancer treatment.

BackgroundOsteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP.MethodsWe performed two‐sample Mendelian randomization (MR) analyses to investigate the causal association between genetically predicted NAFLD [i.e., imaging‐based liver fat content (LFC), chronically elevated serum alanine aminotransferase (cALT) and biopsy-confirmed NAFLD] and risk of OP. The inverse variant weighted method was performed as main analysis to obtain the causal estimates.ResultsImaging-based LFC and biopsy-confirmed NAFLD demonstrated a suggestive causal association with OP ([odds ratio (OR): 1.003, 95% CI: 1.001-1.004, P < 0.001; OR: 1.001, 95% CI: 1.000-1.002, P = 0.031]). The association between cALT and OP showed a similar direction, but was not statistically significant (OR: 1.001, 95% CI: 1.000-1.002, P = 0.079). Repeated analyses after exclusion of genes associated with confounding factors showed consistent results. Sensitivity analysis indicated low heterogeneity, high reliability and low pleiotropy of the causal estimates.ConclusionThe two‐sample MR analyses suggest a causal association between genetically predicted NAFLD and OP.

Under the coupling effect of environment and stray current, concrete railway sleepers will have rust and cracks. The dynamic load of trains exacerbates the crack propagation in the sleepers, thereby reducing their service life. To address this problem, this paper employed the Mesoscale Concrete Model with Real Aggregate Geometry to construct a three-dimensional micro-model of the concrete sleeper, examined the distribution of corrosion current density within the sleepers under various corrosion durations, and investigated the effect of rust accumulation on the steel surface on the sleeper cracking. Moreover, the damage evolution of corroded sleepers under train load was studied. The research results revealed that: (1) The corrosion current density increased rapidly in the early stage of corrosion. After 30 years of corrosion, 10 % of the steel reinforcement protective layer cracked, while after 50 years of corrosion, the cracked area reached 40 %. (2) The maximum thickness of rust accumulation in the middle of the sleeper rebar was 0.4 mm after 30 years of corrosion, and 0.6 mm after 50 years of corrosion. (3) Under the train load, the maximum instantaneous damage increase of the sleepers was 0.314 %, and the maximum damage increase within the 30-year corroded sleepers was 0.05 %.

Introduction A large number of people around the world are exposed to the risks of passive smoking. This prospective study aimed to examine the association between secondhand smoke exposure, exposure time, and the incidence of chronic kidney disease (CKD) and determine whether this association was influenced by genetic susceptibility. Methods The study included 214244 participants of the UK Biobank who were initially free of CKD. Cox proportional hazards model was used to estimate the associations between secondhand smoke exposure time and the risks of CKD in people who have never smoked. The genetic risk score for CKD was calculated by a weighted method. The likelihood ratio test comparing models was used to examine the cross-product term between secondhand smoke exposure and genetic susceptibility to CKD outcomes. Results During a median of 11.9 years of follow-up, 6583 incidents of CKD were documented. Secondhand smoke exposure increased the risk of CKD (HR=1.09; 95% CI: 1.03–1.16, p

Abstract Objective: Dietary transitions in China have undergone rapid changes in over the last three decades. The purpose of this study is to describe trends in the macronutrient consumption, the sources of those nutrients and the diet quality among Chinese adults. Design: Longitudinal China Health and Nutrition Survey (CHNS) cohort analysis. Main outcomes are dietary energy intake from total carbohydrate, protein and fat and their subtypes, as well as food sources of carbohydrates, protein, and fat, and the China Dietary Guidelines Index 2018 (CDGI-2018). Setting: CHNS (1991, 2000, 2009 and 2015). Participants: Data from the longitudinal 1991, 2000, 2009 and 2015 CHNS of adults aged 18 years or older who had complete demographic information. Results: The estimated mean energy intake from total carbohydrate decreased from 62·6 % to 50·6 % between 1991 and 2015, while the mean energy intake from total protein increased from 12·6 % to just 13·1 % and the mean energy intake from total fat significantly increased from 24·0 % to 35·8 % (P < 0·001 for trend). Decreases were observed in evaluated mean energy from low-quality carbohydrates (from 53·6 % to 41·7 %) and incomplete protein (from 9·3 % to 7·5 %), while increases were seen in estimated mean energy from high-quality protein (from 3·3 % to 5·5 %), high-quality fat (from 9·1 % to 16·7 %) and low-quality fat (from 14·9 % to 19·0 %). Low-quality carbohydrates, primarily those derived from refined grains, decreased from 52·2 % to 36·2 %. The diet quality as measured by CDGI-2018 improved, with the estimated mean increasing from 41·7 to 52·4 (P < 0·01 for trend). Conclusion: For Chinese adults, there was a significant change in the macronutrient composition over the previous few decades. The percentage of energy consumed from carbohydrates significantly decreased; however, the percentage of energy consumed from total fat significantly increased. Additionally, the diet quality remains suboptimal.

Driven by the development of intelligent internet of things (IoT) technology, unmanned aerial vehicle (UAV) swarms have been widely used for sensing and monitoring in emergency and rescue scenarios.The UAVs automatically sense and discover mission targets in the mission area, recruiting neighboring UAVs to form perception and computation task groups to collaboratively complete the perception, acquisition and processing of data.However, repetitive sensory data and imbalance in the supply and demand of computational resources between multiple tasks cause additional computational and communication overheads and increase the end-to-end processing latency.To address this challenge, a multi-task resource allocation approach combining bionics and multi-agent independent reinforcement learning was proposed, making collaborative resource allocation decisions based on local task information.The method represents the resource requirements of individual tasks as situational information concentrations and dynamically updates the heterogeneous resource requirements of each task by spreading the situational information across task groups.At the same time, it combines multi-agent independent reinforcement learning methods for intelligent decision making in order to collaboratively allocate the heterogeneous resources of each task.Simulation results show that this solution can not only effectively reduce the task execution time, but also significantly improve the computational resource utilization.

Lung cancer is a major health concern and significant barrier to human well-being and social development. Although targeted therapy has shown remarkable progress in the treatment of lung cancer, the emergence of drug resistance has limited its clinical efficacy. Sijunzi Tang (SJZ) is a classical Chinese herbal formula known for tonifying qi and nourishing the lungs, has been recognized for its potential in lung cancer management. However, the underlying mechanism of its combined use with anti-cancer drugs remains unclear. Here, we investigated the anti-lung cancer efficacy and underlying mechanisms of the combination of gefitinib and SJZ in gefitinib-resistant human lung adenocarcinoma cells (PC-9/GR). We conducted in vitro and in vivo experiments using histopathology and targeted metabolomics approaches. Our results demonstrated that the combination of SJZ and gefitinib exhibited synergistic effects on tumor growth inhibition in PC-9/GR-bearing nude mice. Notably, the co-administration of SJZ and gefitinib synergistically promoted tumor cell apoptosis, potentially through the regulation of BAX and BCL-2 expression. Immunohistochemistry and western blot analysis found down-regulation of GLS, GS, and SLC1A5 expression in the co-administration group compared to the control and the individual treatment groups. Targeted metabolomics revealed significant alterations in the plasma glutamine metabolic markers glutamine, alanine, succinate, glutamate, and pyruvate. Of the glutamine metabolism markers measured in tumor tissues, glutamine and pyruvate demonstrated significant differences across the treatment groups. These findings suggest that administration of SJZ improves gefitinib resistance in the treatment of lung cancer without toxic effects. Moreover, SJZ may affect glutamine metabolism by regulating key targets involved in glutamine metabolism (SLC1A5, GLS, and GS) and modulating the levels of related metabolic markers, ultimately reducing gefitinib resistance.

ObjectiveTo investigate the clinical effect of the da Vinci robotic-assisted laparoscopic pyeloureteroplasty (RALP) in treating pediatric ureteropelvic junction obstruction (UPJO).MethodsWe retrospectively analyzed clinical data from 32 children with UPJO who suffered from RALP in our hospital from October 2020 to February 2023, compared with those treated with common laparoscopy at the same time. After the establishment of the robotic arm, a mesenteric approach was performed after entering the abdominal cavity to focus on the lesion site. The dilated renal pelvis was then cut and the stenotic ureter was removed; the anastomosis and the incision were sutured by layer.ResultsA total of 62 children (44 boys and 20 girls) with a median age of 14 months (ranging from 3 to 38 months) were included. All 62 cases had hydronephrosis caused by unilateral UPJO, and the surgery was successfully completed without conversion to open. All intraoperative blood losses amounted to less than 10 ml. In the RALP group, the average operative duration was 131.28 min (ranging from 108 to 180 min). The average catheter time was 3.66 days (ranging from 2 to 7 days). The average hematuria time was 3.84 days (ranging from 2 to 6 days). The average postoperative hospital stay was 7.8 days (ranging from 6 to 12 days). The average hospitalization costs were 59,048.31 yuan (ranging from 50,484 to 69,977 yuan). The double-J tube was removed 1 month after surgery. Only one patient suffered from complications, developing a urinary tract infection 4 weeks after surgery, and was cured with the administration of oral cefaclor anti-inflammatory drugs for 3 days. All patients were followed up for 2–28 months, with a median follow-up time of 12 months. The thickness of the renal cortex was increased after surgery [(1.95 ± 0.24) vs. (4.82 ± 0.50)] cm, and the isotope renograms revealed a definite recovery of the split renal function [(28.32 ± 1.95) vs. (37.01 ± 2.71)]%.ConclusionThe robotic-assisted laparoscopic pyeloureteroplasty (RALP) in the treatment of children with upper ureteral obstruction has overall clinical efficiency. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

BackgroundChina is witnessing an accelerated aging process and an increasingly serious situation of Parkinson's disease. Research on the pre-disease stage and its related influencing factors has gained more and more attention.ObjectiveTo analyze the current situation of prodromal Parkinson's disease (pPD) of people aged 55 years and above in four provinces of China, and to explore its influencing demographic and socio-economic characteristics.MethodsUsing the data of Community-based Cohort Study on Nervous System Disease in 2020, a total of 10724 participants with complete data on demographic and socio-economic factors and risk factors on Parkinson's disease were selected. Based on the criteria recommended by the International Parkinson and Movement Disorder Society (MDS), we evaluated risk level (i.e., post-test probability) of pPd, prevalence of possible or probable pPD, and number of pPD-related risk/prodromal markers in the participants. Multiple linear regression and multiple logistic regression models were used to analyze the influencing socio-demographic factors of risk level of pPd and prevalence of possible or probable pPD, and Poisson regression and multinomial logit regression models were used to analyze the influencing socio-demographic factors of the number of pPD-related risk/prodromal markers in the total sample, men, and women, respectively.ResultsThe median (P25, P75) of post-test probability of pPD in 2020 was 0.78% (0.42%, 1.66%), the prevalence rate of possible or probable pPD was 0.34%, and 69.03% of the participants reported 3-5 pPD-related risk/prodromal markers. The post-test probabilities of men, those with older age, lower education level, per capita monthly household income < 1000 yuan, urban residency, or without active employment were higher (P

BackgroundChanges in cognitive function exist before the onset of clinical Parkinson's disease. However, studies on association between cognitive function and prodromal Parkinson's disease (pPD) are limited.ObjectiveTo estimate probability of pPD and assess its association with global and domain cognitive function in Chinese elders.MethodsData were drawn from the Community-based Cohort Study on Nervous System Disease 2018 (baseline) and 2020 (follow-up). We selected 3911 residents aged 55 and above who participated the two waves, without Alzheimer's disease and Parkinson's disease, and with completed information on demographics, disease history, cognitive function test, and risk factors of Parkinson's disease. Cognitive function was assessed using the Chinese version of Montreal Cognitive Assessment Scale. Calculation of probability of pPD and assessment of possible (probability between 30% and

With the expansion of aging population in China, the increasingly serious situation of Parkinson's disease (PD) threatens the physical and mental health and quality of life of middle-aged and elderly people, posing a great challenge to increase healthy life expectancy and realize the Healthy China Strategy. Previous studies showed some connections between dietary and lifestyle factors and PD and suggested that excessive intake of red meat might increase the risk of PD; however, coffee and tea, dietary antioxidants, n-3 polyunsaturated fatty acids, vitamin D, and vitamin B were associated with reducing the risk of PD or delaying the progression of PD, and dietary patterns with high intakes of fresh vegetables and fruits, legumes, whole grains, fish, and poultry meat were also associated with a reduced risk of PD. In addition, physical activity was a protective factor for PD, and smoking was also associated with a reduced risk of PD, but the related mechanisms were still unclear. This paper evaluated the relationships of factors like foods, nutrients, dietary patterns, and lifestyle with PD based on published literature, summarized the limitations of relevant studies, and provided useful enlightenment for PD prevention and control.

BackgroundIt has been reported that a high intake of dairy products might be associated with an increased risk of Parkinson's disease (PD) in foreign studies, but no such study has yet been conducted on prodromal Parkinson's disease (pPD) and the Chinese population. ObjectiveTo investigate the prospective relationship between the intake of dairy products and pPD among people aged 55 and above in four provinces of China. MethodsThe research data were obtained from the baseline 2018 and follow-up 2020 surveys of Community-based Cohort Study on Nervous System Disease. A total of 9984 residents were selected who participated in both waves of surveys and had complete data on demographics, dietary products intake, and risk factors for PD. We evaluated the risk level and the numbers of related risk/prodromal markers of pPD in the participants based on a criteria recommended by the International Parkinson and Movement Disorder Society (MDS). Food Frequency Questionnaire was used to obtain food consumption data in the past 12 months, and the intake of dairy products was calculated and divided into non-consumption and tertiles of consumption (T1, T2, and T3 from low to high). Multiple linear regression was used to analyze the association between baseline dairy intake and risk level of follow-up pPD. Poisson regression and multinomial logit regression models were used to analyze the relationship of baseline dairy products and the number of risk/prodromal markers of follow-up pPD in the population, and multiple logistic regression was used to analyze each risk/prodromal marker of follow-up pPD according to baseline levels of dairy products intake. ResultsThe percentage of residents without dairy products consumption was 58.02% in 2018, and the dairy products intakes were relatively high among residents being female, aged 55 to 74 years, with an education level of middle school and above, with a per capita monthly household income ≥ 1000 yuan, living in urban areas, and without active employment (P

BackgroundGastrointestinal microbiota plays an important role in the development of Parkinson's disease (PD), and dietary factors have a great impact on intestinal micro ecology. At present, few studies focus on red meat and PD, especially prodromal PD (pPD). ObjectiveTo understand the relationships of the intake of red meat and processed meat products with pPD and the number of risk/prodromal markers, and to explore the association of dietary factors with pPD. MethodsBased on the data of Community-based Cohort Study on Nervous System Disease in 2018 and 2020, adults aged 55 years and older with complete demographic information, dietary survey information, and information on risk factors related to PD were selected from four provinces of China. After excluding those reporting abnormal total energy intake or those reporting alcohol drinking or abused drugs for a long period of time, and confirmed mental diseases with prescribed drugs, a total of 10003 subjects were included. Food frequency questionnaire was used to calculate the intake of red meat and processed meat products. The pPD-related risk/prodromal markers were selected following the International Parkinson and Movement Disorder Society criteria for pPD, and the risk level and the number of markers of pPD were then calculated. The relationship between the intake of red meat and processed meat and the risk level of pPD was analyzed by multiple linear regression. The relationship between the intake of red meat and processed meat and the pPD marker number groups was analyzed by multinomial logit regression model. ResultsIn 2018, the intake of red meat and processed meat was 28.57 g·d−1 in the target population. In 2020, the median of the number of risk/prodromal markers was 3, and the median M (P25, P75) of the posterior probability of pPD was 0.74% (0.42%, 1.49%). The multiple linear regression analysis showed that the higher the intake of red meat and processed meat, the higher the risk level of pPD in follow-up (b=0.021, P

Abstract In this study, we established a novel immunologic gene prognostic index (IGPI) to predict metastasis and provided new insights into tumor immune microenvironment (TIME) for PCa patients receiving radical radiotherapy. GBP2 and IGF1 were independent factors associated with metastasis-free survival. IGPI score was calculated based on GBP2 and IGF1 and this score was an independent risk factor for PCa patients undergoing radical radiotherapy. Patients with higher IGPI score were at higher risk of metastasis and biochemical recurrence, which were externally validated in the TCGA database and other GEO datasets. IGPI score had demonstrated moderate diagnostic ability of radiation resistance (AUC: 0.889). This score increased with the augment of Gleason score and T stage, as well as biochemical recurrence. Using EPIC, ESTIMATE and immunophenoscore (IPS) algorithms, cancer associated fibroblasts (CAFs), macrophages, stromal score, and estimate score were significantly higher in patients with metastasis group compared to their counterpart. Besides, for CAFs, macrophages, stromal score, and estimate score, patients with higher scores were at higher risk of metastasis, and the HRs were 3.65, 4.01, 4.27, and 3.78, respectively. IGPI score was highly positively associated with stromal score (coefficient: 0.39), immune score (coefficient: 0.43), estimate score (coefficient: 0.45), CAFs (coefficient: 0.42) and macrophages (coefficient: 0.42), while showing the opposite relationship with tumor purity (coefficient: − 0.45). In conclusion, we found that IGPI based on GBP2 and IGF1 might serve as a biomarker predicting metastasis for PCa patients. Besides, the current data further highlight the importance of CAFs in the metastatic process of PCa.

Plain English summary Malignant tumors of the female reproductive system are the leading causes of women's mortality worldwide, mainly including cervical cancer, uterine cancer and ovarian cancer. Numerous studies have reported mortality changes in the three primary reproductive system cancers among different countries, with inconsistent temporal trends. In 2020, almost 17.51% of malignant tumors of the female reproductive system deaths occurred in China because of the large population base and severe aging. However, there are limited studies on the disease burden of malignant tumors of the female reproductive system in China. This study analyzed the mortality, YLL and LLE of cervical cancer, uterine cancer and ovarian cancer using the National Death Cause Surveillance Dataset from 2006 to 2020. The findings revealed that mortality and disease burden of malignant tumors of the reproductive system showed no significant change. The mortality and disease burden of uterine cancer decreased significantly, but that of cervical cancer and ovarian cancer remain high. Cervical cancer has a higher mortality and disease burden than uterine cancer and ovarian cancer, making it the most severe malignant tumor of the female reproductive system. Screening and HPV vaccination will reduce the mortality and disease burden of cervical cancer in China, but this effect will take many years to manifest. Screening and prevention strategies for high-risk groups of uterine cancer and ovarian cancer should be established as soon as possible. In summary, the management and monitoring of malignant tumors of the female reproductive system should be strengthened.

Abstract Background Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer’s disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

Lunasin protease inhibitor concentrate (LPIC) is a novel combination of soy bioactive peptide lunasin, Kunitz and Bowman-Birk protease inhibitors. The reported anti-inflammatory and anticancer properties of each one of them suggest LPIC as a promising candidate for the treatment of inflammatory-related diseases. Our objective was to assess the in vivo anti-inflammatory properties of LPIC. First, an in vitro test was performed in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophages by measuring the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) as inflammatory markers. For the in vivo model, ulcerative colitis (UC) was induced in mice via oral administration of dextran sodium sulfate (DSS). LPIC treatment was performed via daily intraperitoneal injection of 50 mg/kg body weight. Body weight, visible blood in stool and stool consistency were scored daily as macroscopic indicators of disease progression. Occult blood was evaluated by the presence of hemoglobin in stool every third day. Colon length, caecum weight, colonic myeloperoxidase activity (MPO), presence of pro-inflammatory cytokines in blood and colon, changes in the architecture, and expression of inducible nitric oxide synthase (iNOS) in colonic tissue were evaluated. In vitro, LPIC induced production of NO and maintained cytokine levels in comparison to activated untreated macrophages. In vivo, LPIC increased colonic bleeding and did not improve macroscopic markers of the disease, but reduced colonic IL-1β and IL-6, decreased systemic circulation of TNF-α, attenuated neutrophils infiltration and iNOS expression in colonic tissue, and diminished the damage in colonic architecture. Our results suggest that combinations of peptides in LPIC may counteract the anti-inflammatory properties in vitro; while in vivo, LPIC can significantly reduce the histopathological damage, hence is a possible therapeutic strategy to attenuate UC.

Abstract Background The 2020 coronavirus pandemic (COVID-19) has been raging for more than 20 months, putting significant strain on public health systems around the world. Despite the fact that the pandemic has been effectively managed in certain countries, regional outbreaks and viral mutations continue to pose a threat to people's lives. The likelihood of post-pandemic changes in people's psychological situations warrants more investigation. Design and participants This study was conducted in the context of another outbreak in Zhangjiajie, China, respondents (infected patients, healthy population) were required to complete self-administered questions and standardized questionnaires, including the patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder-7 (GAD-7), and the Brief Illness Perception Questionnaire (BIPQ). Measures We conducted an anonymous questionnaire survey of infected patients (excluding critically ill patients) in the confirmed COVID-19 ward of Zhangjiajie City People's Hospital's East Hospital from August 14 to 24, 2021, and used convenience sampling to survey medical staff and the general public to assess the psychological reactions of different populations during the delta variant outbreak pandemic. Differences in anxiety and depression severity were compared between groups, with logistic regression models constructed to explore potential factors associated with scoring clinical significant levels of depression and/or anxiety. Results There is no significant difference (p value = 0.228) between anxiety and depression in patients (n = 53), general public (n = 97), medical personnel (n = 103), and support workers (n = 65). Females reported higher scores on the GAD-7 and the BIPQ, reduced communication with family and friends appeared to be a risk factor for clinically significant anxiety and depression. Conclusions There were no significant differences in anxiety and depression across populations explored in this study, but females had higher anxiety and illness perception than males, and effective communication may help improve mental health.

BackgroundMagnesium plays an important physiological role in human, but the association between dietary magnesium intake and the risk of hypertension is unclear. Few studies have reported the dose-response relationship in Chinese population. ObjectiveTo analyze the relationship between dietary magnesium intake and the risk of hypertension in Chinese adults aged 18-64 years, and to explore the dose-response relationship. MethodsA total of 13082 adults aged 18-64 years who participated in at least two rounds of the China Health and Nutrition Survey (CHNS) from 2000 to 2018 were selected. Dietary data were obtained by consecutive 3-day 24-hour dietary recall and weighting & bookkeeping method. Blood pressure was measured with a standard mercury sphygmomanometer. Hypertension was diagnosed when systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or self-reported hypertension history or using antihypertensive drugs. The mean of dietary magnesium intake in all survey years (excluding the last survey) was used as the dietary magnesium intake of the subject, and the mean of dietary magnesium intake was divided into 5 equal groups. Cox proportional risk model with adjustments for socio-demographic factors, body mass index (BMI), smoking and drinking, sleep time, physical activity, and dietary factors, was used to analyze the association between dietary magnesium intake and the risk of hypertension. A sensitivity analysis was conducted by excluding baseline diabetes patients and adjusting for baseline blood pressure. In addition, a restricted cubic spline model was used to analyze the dose-response relationship between them. ResultsIn this study, male participants accounted for 47.70%, and those aged 18-44 years accounted for 72.47%. The mean follow-up time was 12.56 years and the prevalence of hypertension was 13.86%. Dietary magnesium intake was inversely associated with the risk of hypertension at the 4th quintile (median 333.56 mg·d−1) and the 5th quintile (median 420.07 mg·d−1) compared with the 1st quintile (median 189.06 mg·d–1), and the hazard risk (HR) values and associated 95%CIs were 0.81 (0.67-0.97) and 0.81 (0.66-0.99) respectively. After eliminating baseline diabetes and adjusting baseline blood pressure, dietary magnesium intake remained negatively associated with the risk of hypertension, which was consistent with the population-wide HR. The association between dietary magnesium intake and the risk of hypertension was non-linear (χ2=11.07, P=0.01). When dietary magnesium intake was higher than 339 mg·d−1, the risk of hypertension decreased, and the HR value was the lowest in 375-418 mg·d−1 (HR=0.65, 95%CI: 0.45-0.94), and then gradually tended to 1. There was no statistically significant association at 467 mg·d−1 and above.ConclusionMagnesium intake in the range of 339-467 mg·d−1 is negatively associated with the risk of hypertension in Chinese adults, presenting a U-shaped dose-response relationship.

BackgroundDiabetes is a major contributor to global burden of disease. The role of magnesium in the prevention of diabetes has aroused concern. However, the research results on the impact of dietary magnesium on the risk of diabetes are hitherto inconsistent. ObjectiveTo evaluate the association between dietary magnesium intake and the risk of diabetes through a systematic review. MethodsPubMed, Web of Science, China National Knowledge Infrastructure, Wanfang databases were searched for prospective studies that contained risk estimates for magnesium intake-associated diabetes and were published from January 1, 2000 to December 31, 2021. Two researchers independently screened the literature according to a set of pre-prepared inclusion and exclusion criteria, extracted the data according to an unified data extraction table, and evaluated the quality of included articles with Newcastle-Ottawa Scale (NOS). R 4.0.3 software and Stata SE16.0 software were used for meta-analysis and subgroup meta-analysis, and Higgins I2 statistics were used to test the heterogeneity of the included studies. The sources of heterogeneity were analyzed by univariate meta regression. ResultsA total of 14 articles involving 17 prospective cohort studies (1065267 participants and 40506 patients with diabetes) were included in the study. The NOS scores ranged from 8 to 9, with an average of 8.6, indicating that the included studies were classified as being high quality. The highest quintile of magnesium intake group reduced the risk of diabetes by 22% (RR=0.78, 95%CI: 0.73-0.82) compared with the lowest quintile group. This association was not substantially modified by geographic region, sex, or follow-up length. The highest quintile of dietary magnesium intake in the Americas and Asia were associated with 22% and 26% reductions in the risk of type 2 diabetes respectively compared with the lowest quintile group (the Americas, RR=0.78, 95%CI: 0.73-0.84; Asia, RR=0.74, 95%CI: 0.63-0.88); The highest quintile of dietary magnesium intake in female, male and without gender stratified were associated with 22%, 19% and 46% reductions in the risk of type 2 diabetes respectively compared with the lowest quintile group (Female RR=0.78, 95%CI: 0.73-0.84; Male RR=0.81, 95%CI: 0.74-0.89; Both RR=0.54, 95%CI: 0.42-0.68); Compared with the lowest quintile groups, the groups with the highest quintile of dietary magnesium intake with a follow-up time of less than 10 years and more than 10 years reduced the risk of type 2 diabetes by 26% and 20% respectively (≤10 years, RR=0.74, 95%CI: 0.65-0.83; ＞10 years, RR=0.80, 95%CI: 0.75-0.85). After adjusting for hypertension, the highest quintile of dietary magnesium intake group reduced the risk of type 2 diabetes by 20% compared with the lowest quintile group (RR=0.80, 95%CI: 0.74-0.85). The year of publication (P

BackgroundAt present, domestic and foreign studies on the association between dietary magnesium and diabetes risk are not consistent, and there are relatively few prospective studies in China and the study population is relatively limited. ObjectiveTo explore the association between dietary magnesium intake and diabetes risk in Chinese adults in 15 provinces (autonomous regions, municipalities), and to provide a scientific basis for revising dietary magnesium intake reference for Chinese residents. MethodsA total of 8061 adults aged 18-64 who participated in at least two follow-up surveys in the China Health and Nutrition Survey in 2009, 2015, and 2018, had complete survey data, and did not report diabetes at baseline were selected as subjects. Food consumption data were collected from 3-day 24-hour dietary recalls and by weighing household cooking oil and condiments. The average daily dietary magnesium intake was calculated based on the food composition table. Multiple Cox proportional risk regression model and restricted cubic spline (RCS) model were used to analyze the association and dose-response relationship between dietary magnesium intake and diabetes risk. Diabetes was defined according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 edition). ResultsA total of 47237.46 person-years were followed up, with an average follow-up of 5.86 years. Among 8061 subjects, the incidence rate was 8.86%. Compared with those in the top quintile of magnesium intake (Q5), those with lower dietary magnesium intake were more likely to be female, have higher income, higher education, live in urban areas, and have lower intakes of energy, dietary fiber, and dietary calcium. After adjusting for demographic characteristics, lifestyle, and dietary factors, compared with adults in the lowest quintile of dietary magnesium intake, the results of Cox proportional risk regression model showed that the second (median: 220.96 mg·d−1), third (median: 263.01 mg·d−1), and fourth (median: 312.33mg·d−1) quintile dietary magnesium intake reduced the risk of diabetes by 45% (HR=0.55, 95%CI: 0.43-0.71), 39% (HR=0.61, 95%CI: 0.47-0.78), and 34% (HR=0.66, 95%CI: 0.51-0.78), respectively. The results of RCS analysis showed that dietary magnesium intake and the risk of diabetes were U-shaped overall. Taking the 5th percentile magnesium intake as reference, when dietary magnesium intake was lower than 240 mg·d−1, the risk of diabetes gradually decreased with the increase of magnesium intake; the risk was the lowest at 240 mg·d−1, followed by a slight increase in risk at 240-400 mg·d−1; and no statistical difference presented in the association between dietary magnesium and diabetes risk after 650 mg·d−1. ConclusionThe study findings suggest an association between dietary magnesium intake and diebetes risk. The association is negative and non-linear when dietary magnesium intake is below 240 mg·d−1.