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Abstract To address the fatigue damage issues in continuous beam bridges under vehicle loads, a method using vibration-mixed steel fiber-reinforced concrete to improve critical vulnerable areas of the bridge is proposed, thereby enhancing the bridge’s fatigue resistance. Fatigue performance and micro electron microscopy tests were designed for vibration-mixed steel fiber-reinforced concrete, analyzing its damage conditions and microstructural changes under 0 to 2 million cyclic loads, and the key mechanical parameters of the concrete were determined. Based on this, a numerical analysis model was established to simulate the fatigue damage of continuous beam bridges under moving vehicle loads. The results show that piers made with vibration-mixed steel fiber-reinforced concrete exhibit a 56.86% reduction in compressive damage compared to conventional piers, a reduction in stiffness damage range, and a 29.35% increase in fatigue life.

Abstract Background Chronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia. Methods This was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients’ sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events. Results Throughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference − 1.10; 95% confidence interval (CI), − 1.82 to − 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference − 2.14; 95% CI, − 2.90 to − 1.38; p

Abstract Background Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. Methods We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Results Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Conclusion Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Abstract Objective Accumulation of extracellular matrix (ECM) proteins in the glomerular mesangial region is a typical hallmark of diabetic nephropathy (DN). However, the molecular mechanism underlying ECM accumulation in the mesangium of DN patients remains unclear. The present study aims to establish a connection between extracellular proteins and DN with the goal of identifying potential biomarkers for this condition. Methods Differentially expressed genes (DEGs) between DN kidney tissue and healthy kidney tissue were analyzed using the public data GSE166239. Two gene lists encoding extracellular proteins were then utilized to identify extracellular protein-differentially expressed genes (EP-DEGs). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed on these EP-DEGs. A protein–protein interaction (PPI) network was established to identify key EP-DEGs. Furthermore, the diagnostic ability, immune cell infiltration, and clinical relevance of these EP-DEGs were investigated. Immunohistochemistry (IHC) staining of paraffin-embedded renal tissues was performed to validate the accuracy of the bioinformatic results. Results A total of 1204 DEGs were identified, from which 162 EP-DEGs were further characterized by overlapping with extracellular protein gene lists. From the PPI network analysis, five EP-DEGs (e.g., TNF, COL1A1, FN1, MMP9, and TGFB1) were identified as candidate biomarkers. TNF, COL1A1, and MMP9 had a high diagnostic accuracy for DN. Assessment of immune cell infiltration revealed that the expression of TNF was positively associated with resting dendritic cells (DCs) (r = 0.85, P

Abstract Weight-adjusted waist index (WWI) is a new marker of central obesity. This study explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes or prediabetes. 6551 participants with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) records between 2005 and 2018 were included. The association of WWI with all-cause and CVD mortality was assessed using Kaplan-Meier survival analysis, Cox proportional hazards model (Cox regression), and restricted cubic spline (RCS). The predictive value of WWI for mortality was analyzed using time-dependent receiver operating characteristic curves (ROC). There were 1083 all-cause deaths and 360 CVD deaths. Multivariable-adjusted Cox regression analyses showed WWI was positively correlated with the risk of all-cause and CVD mortality in subjects with diabetes or prediabetes. Multivariate-adjusted RCS analyses showed a linear and positive correlation of WWI with all-cause mortality risk, and a nonlinear relationship with CVD mortality, with a threshold of 12.35. The area under the curve (AUC) for 3, 5, and 10-years survival for all-cause mortality was 0.795, 0.792, and 0.812, respectively, and for CVD mortality was 0.815, 0.833, and 0.831, respectively. WWI is a valuable predictor of all-cause mortality risk in patients with diabetes and prediabetes, and a valuable predictor of CVD mortality risk when patients with diabetes and prediabetes are considered as a whole.

Abstract The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Curative resection stands as the sole potential cure for gallbladder cancer (GBC); nevertheless, a dearth of knowledge persists regarding long-term follow-up data and prognostic factors that hinder achieving a cure post-surgery. A retrospective cohort study was conducted by analyzing pathologically confirmed initial resections for GBC between 2000 and 2013 across three Chinese medical centers. The concept of observed cure refers to a 10-year survival period devoid of any disease recurrence. Employing a semiparametric proportional hazards mixture cure model enabled the identification of clinicopathological factors impeding a cure for GBC post-surgery. In our current study, a total of 331 patients were included, with a follow-up period exceeding a decade. The median overall survival (OS) was recorded at 31.6 months, with 39 patients (11.78%) achieving a 10-year OS, classified as 10-year survivors. Within this subset, 36 patients reached a 10-year relapse-free survival, denoting cure, and yielding an observed cure rate of 10.88%. Notably, factors such as combined surgical resection involving invaded organs, positive lymph node metastasis, and R1 resection (below 1%) were identified as virtually precluding a cure. Additionally, patients with T3–4 stage, hepatic invasion, advanced AJCC stage or poor tumor differentiation exhibited a low likelihood of achieving cure (below 5%). The discovery of these prognostic factors holds significant value in tailoring individualized treatment strategies and enhancing clinical decision-making processes.

Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

Objectives To compare the level of knowledge of depression, recognition ability and attitudes towards depression among urban and rural residents in Beijing.Design A cross-sectional study.Setting Six districts in Beijing, China, 2021.Participants A total of 6463 participants aged 18 years and above who had lived for more than 6 months over the last year in Beijing were selected in this study.Outcome The awareness and recognition of depression and the views of residents towards people with depression.Results A total of 2554 urban and 2043 rural residents completed the survey. Urban residents of Beijing exhibited a higher average total score on the Depression Knowledge Questionnaire [(20.4±3.3) vs (18.7±3.5), p

Abstract In the evolving landscape of smart libraries, this research pioneers an IoT-based low-cost architecture utilizing Software-Defined Networking (SDN). The increasing demand for more efficient and economical solutions in library management, particularly in the realm of RFID-based processes such as authentication, property circulation, and book loans, underscores the significance of this study. Leveraging the collaborative potential of IoT and SDN technologies, our proposed system introduces a fresh perspective to tackle these challenges and advance intelligent library management. In response to the evolving landscape of smart libraries, our research presents an Internet of Things (IoT)-based low-cost architecture utilizing SDN. The exploration of this architectural paradigm arises from a recognized gap in the existing literature, pointing towards the necessity for more efficient and cost-effective solutions in managing library processes. Our proposed algorithm integrates IoT and SDN technologies to intelligently oversee various library activities, specifically targeting RFID-based processes such as authentication, property circulation management, and book loan management. The system's architecture, encompasses components like the data center, SDN controllers, RFID tags, tag readers, and other network sensors. By leveraging the synergy between RFID and SDN, our innovative approach reduces the need for constant operator supervision in libraries. The scalability and software-oriented nature of the architecture cater to extensive library environments. Our study includes a two-phase investigation, combining practical implementation in a small-scale library with a simulation environment using MATLAB 2021. This research not only fills a crucial gap in current knowledge but also lays the foundation for future advancements in the integration of IoT and SDN technologies for intelligent library management.

Abstract Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases. However, concerns over the safety and efficacy require to be further addressed in order to realize their full potential. Synthetic receptors, a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules, have been rapidly developed and applied as a powerful solution. Delicately designed and engineered, they can be applied to finetune the therapeutic activities, i.e., to regulate production of dosed, bioactive payloads by sensing and processing user-defined signals or biomarkers. This review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical research. With a special focus on four synthetic receptor systems at the forefront, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, we address the generalized strategies to design, construct and improve synthetic receptors. Meanwhile, we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

Abstract Background With the development of cancer precision medicine, a huge amount of high-dimensional cancer information has rapidly accumulated regarding gene alterations, diseases, therapeutic interventions and various annotations. The information is highly fragmented across multiple different sources, making it highly challenging to effectively utilize and exchange the information. Therefore, it is essential to create a resource platform containing well-aggregated, carefully mined, and easily accessible data for effective knowledge sharing. Methods In this study, we have developed “Consensus Cancer Core” (Tri©DB), a new integrative cancer precision medicine knowledgebase and reporting system by mining and harmonizing multifaceted cancer data sources, and presenting them in a centralized platform with enhanced functionalities for accessibility, annotation and analysis. Results The knowledgebase provides the currently most comprehensive information on cancer precision medicine covering more than 40 annotation entities, many of which are novel and have never been explored previously. Tri©DB offers several unique features: (i) harmonizing the cancer-related information from more than 30 data sources into one integrative platform for easy access; (ii) utilizing a variety of data analysis and graphical tools for enhanced user interaction with the high-dimensional data; (iii) containing a newly developed reporting system for automated annotation and therapy matching for external patient genomic data. Benchmark test indicated that Tri©DB is able to annotate 46% more treatments than two officially recognized resources, oncoKB and MCG. Tri©DB was further shown to have achieved 94.9% concordance with administered treatments in a real clinical trial. Conclusions The novel features and rich functionalities of the new platform will facilitate full access to cancer precision medicine data in one single platform and accommodate the needs of a broad range of researchers not only in translational medicine, but also in basic biomedical research. We believe that it will help to promote knowledge sharing in cancer precision medicine. Tri©DB is freely available at www.biomeddb.org , and is hosted on a cutting-edge technology architecture supporting all major browsers and mobile handsets.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Abstract Thrombospondin1 (TSP1) is a multifunctional matricellular protein. Previously, we demonstrated that TSP1 plays a pivotal role in obesity-related inflammation and insulin resistance (IR) by modulating macrophage accumulation and activation in adipose tissue. Moreover, in our in vitro studies, a CD36-derived peptide, functioning as a TSP1 antagonist, effectively inhibited TSP1-induced proinflammatory macrophage activation. However, whether this CD36 peptide can inhibit obesity-induced inflammation and IR in vivo is unknown and determined in this study in a high fat diet-induced obese mouse model (DIO). CD36 peptide or control peptide was intraperitoneally administered into the established obese mice triweekly for 6 weeks. We found that CD36 peptide treatment didn’t affect obesity or weight gain but significantly reduced proinflammatory cytokine production systemically and in visceral fat tissue. Adipose tissue exhibited fewer crown-like structures and reduced macrophage infiltration. CD36 peptide treatment also attenuated the proinflammatory phenotype of bone marrow derived macrophages from obese mice. Furthermore, CD36 peptide treatment improved glucose tolerance and insulin sensitivity, and mitigated obesity-related fatty liver disease and kidney damage. Collectively, this study suggests that the CD36 peptide, as a TSP1 antagonist, shows promise as a novel therapeutic approach for managing obesity-related metabolic disorders.

Abstract Background Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. Methods The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. Results KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p

Abstract To investigate the hot topics and attitudes of autism in the larger community. In this study, we analyzed and summarized experimental texts from the social media platform Zhihu using the TF-IDF algorithm and K-means clustering approach. Based on the analysis of the 1,740,826-word experimental text, we found that the popularity of autism has steadily risen over recent years. Sufferers and their parents primarily discuss autism. The K-means clustering algorithm revealed that the most popular topics are divided into four categories: self-experience of individuals with autism, external views of individuals with autism, caring and stressful behaviors of caregivers, and information about autism. This study concluded that people with autism face more incredible negative emotions, external cognitive evaluations of the autistic group reflect stereotypes, the caregiver’s family suffers high financial and psychological stress, and disorders caused by disease in autistic individuals.

Abstract Background Patients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation. Methods In AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC–MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman. Results AP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman’s activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages’ activation. Conclusions The enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation. Graphical Abstract

Background In papillary thyroid carcinoma (PTC) patients with Hashimoto’s thyroiditis (HT), preoperative ultrasonography frequently reveals the presence of enlarged lymph nodes in the central neck region. These nodes pose a diagnostic challenge due to their potential resemblance to metastatic lymph nodes, thereby impacting the surgical decision-making process for clinicians in terms of determining the appropriate surgical extent. Methods Logistic regression analysis was conducted to identify independent risk factors associated with central lymph node metastasis (CLNM) in PTC patients with HT. Then a prediction model was developed and visualized using a nomogram. The stability of the model was assessed using ten-fold cross-validation. The performance of the model was further evaluated through the use of ROC curve, calibration curve, and decision curve analysis. Results A total of 376 HT PTC patients were included in this study, comprising 162 patients with CLNM and 214 patients without CLNM. The results of the multivariate logistic regression analysis revealed that age, Tg-Ab level, tumor size, punctate echogenic foci, and blood flow grade were identified as independent risk factors associated with the development of CLNM in HT PTC. The area under the curve (AUC) of this model was 0.76 (95% CI [0.71–0.80]). The sensitivity, specificity, accuracy, and positive predictive value of the model were determined to be 88%, 51%, 67%, and 57%, respectively. Conclusions The proposed clinic-ultrasound-based nomogram in this study demonstrated a favorable performance in predicting CLNM in HT PTCs. This predictive tool has the potential to assist clinicians in making well-informed decisions regarding the appropriate extent of surgical intervention for patients.

Objectives This study aimed to describe the frequency, determinants and outcomes for assessment of patients who had an acute ischaemic stroke (AIS) for rehabilitation during hospitalisation in China.Design A registry-based retrospective observational study.Study design and settings Data regarding assessment or rehabilitation were extracted from the Chinese Stroke Center Alliance database from 1 August 2015 to 31 July 2019. Univariate and multivariate analyses were conducted to identify patient and hospital characteristics associated with rehabilitation assessment during acute hospitalisation as well as discharge outcomes.Study cohort We included 837 897 patients who had a stroke in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital designation.Primary and secondary outcome measures Rehabilitation assessment and discharge outcomes.Results Among 837 897 patients who had a stroke admitted to 1473 hospitals, 615 991 (73.5%) underwent rehabilitation assessment. There were significant variations in the rates of rehabilitation assessment across hospitals (IQR 61.3% vs 92.9%). According to multivariate analysis, guideline recommended care delivery was associated with a higher rehabilitation assessment rate, whereas high/low body mass index, ambulation (OR 0.88; 95% CI 0.87 to 0.90), history of stroke (OR 0.94; 95% CI 0.93 to 0.95), coronary heart disease (OR 0.84; 95% CI 0.82 to 0.85) and atrial fibrillation (OR 0.91; 95% CI 0.89 to 0.94) were associated with a lower rate. Additionally, rehabilitation assessment during hospitalisation was significantly associated with lower in-hospital mortality (OR 0.38; 95% CI 0.35 to 0.41) and a higher probability of discharge to a rehabilitation centre (OR 2.66; 95% CI 2.5 to 2.82).Conclusions Nearly one-quarter of patients who had an AIS do not undergo documented rehabilitation assessment and compliance across hospitals varies. Thus, it is necessary to improve adherence to rehabilitation assessment to improve the quality of medical care for patients who had an AIS.

Abstract Background Osteosarcoma (OS) has been the most common malignancy of the bone in children and adolescents, and the unsatisfactory prognosis of OS sufferers has long been a hard nut. Here, we delved into the markers with a prognostic value for predicting the prognosis of OS patients. Methods The messenger RNA (mRNA) sequencing data and clinical data of OS were retrieved from a Gene Expression Omnibus (GEO) dataset (GSE39058). Next, prognosis-related genes (PRGs) were filtered with the aid of Kaplan–Meier (K-M) curves and Cox regression analysis (CRA). Later, Gene Ontology (GO) biological process analysis was used in verifying the function of different genes. CCK-8 and cell apoptosis assay were performed to evaluate the function of MFNG in U2OS cells. Results Among the obtained genes, Manic Fringe (MFNG) had the closest relevance to prognosis and clinical traits, thus becoming the research object herein. In light of the expression level of MFNG, patients fell into high- and low-MFNG groups. Patients with elevated MFNG expression had a worse prognosis, according to the survival analysis. It was unveiled by the univariate and multivariate analyses that MFNG expression was an independent adverse prognostic factor for disease-free survival in OS patients (p = 0.006). Meanwhile, MFNG expression was linked to gender and tumor recurrence, and it was higher in patients with OS recurrence. Moreover, overexpression of MFNG promoted the cell proliferation and inhibited the cell apoptosis of U2OS cells. Conclusions The expression level of MFNG negatively correlated with OS progression, and as an independent adverse prognostic factor for disease-free survival in OS patients. Moreover, MFNG regulated the cell proliferation and apoptosis of OS cells.

Abstract As an important bioactive molecule, nitric oxide (NO) can effectively alleviate the effects of drought stress on crops. However, it is still unclear whether it can increase the stress resistance of soybean. Therefore, in this study, our objective was to explore the effect of exogenous NO application on the physiological characteristics of soybean seedlings under drought stress. As test material, two soybean varieties, HN65 and HN44, were used, while sodium nitroprusside (SNP) of 100 μmol L−1, 200 μmol L−1, 500 μmol L−1, 1000 μmol L−1 served as an exogenous NO donor, and PEG-6000 as an osmotic regulator to simulate drought stress. The effects of irrigation with different SNP concentrations for different days on the physiological characteristics of the soybean seedlings under drought conditions were then investigated. The results obtained showed that the activities of antioxidant enzymes, osmotic regulator contents, as well as the abscisic acid and salicylic acid contents of the plant leaves increased with increasing SNP concentration and treatment time. However, we observed that excessively high SNP concentrations decreased the activities of key nitrogen metabolism enzymes significantly. This study provides a theoretical basis for determining a suitable exogenous NO concentration and application duration. It also highlights strategies for exploring the mechanism by which exogenous NO regulates crop drought resistance.

Abstract When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length–width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily.

Abstract Metabolic reprogramming has been defined as a key hall mark of human tumors. However, metabolic heterogeneity in gastric cancer has not been elucidated. Here we separated the TCGA-STAD dataset into two metabolic subtypes. The differences between subtypes were elaborated in terms of transcriptomics, genomics, tumor-infiltrating cells, and single-cell resolution. We found that metabolic subtype 1 is predominantly characterized by low metabolism, high immune cell infiltration. Subtype 2 is mainly characterized by high metabolism and low immune cell infiltration. From single-cell resolution, we found that the high metabolism of subtype 2 is dominated by epithelial cells. Not only epithelial cells, but also various immune cells and stromal cells showed high metabolism in subtype 2 and low metabolism in subtype 1. Our study established a classification of gastric cancer metabolic subtypes and explored the differences between subtypes from multiple dimensions, especially the single-cell resolution.

This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. In vivo, Sprague–Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib. Blood samples were collected and subjected to UPLC-MS/MS analysis. An enzyme incubation assay was performed to investigate the mechanism of drug–drug interaction using both rat and human liver microsomes (RLM and HLM). The results showed that icotinib markedly increased the AUC(0–t) and AUC(0–∞) of oxycodone but decreased the CLz/F. The Cmax of oxycodone increased significantly upon co-administration of apatinib. In vitro, the Km value of oxycodone metabolism was 101.7 ± 5.40 μM and 529.6 ± 19.60 μM in RLMs and HLMs, respectively. Icotinib and apatinib inhibited the disposition of oxycodone, with a mixed mechanism in RLM (IC50 = 3.29 ± 0.090 μM and 0.95 ± 0.88 μM, respectively) and a competitive and mixed mechanism in HLM (IC50 = 22.34 ± 0.81 μM and 0.48 ± 0.05 μM, respectively). In conclusion, both icotinib and apatinib inhibit the metabolism of oxycodone in vitro and in vivo. Therefore, the dose of oxycodone should be reconsidered when co-administered with icotinib or apatinib.

Abstract tsRNAs (tRNA-derived small RNAs), as products of the stress response, exert considerable influence on stress response and injury regulation. However, it remains largely unclear whether tsRNAs can ameliorate liver injury. Here, we demonstrate the roles of tsRNAs in alleviating liver injury by utilizing the loss of NSun2 (NOP2/Sun domain family, member 2) as a tsRNAs-generating model. Mechanistically, the loss of NSun2 reduces methyluridine-U5 (m5U) and cytosine-C5 (m5C) of tRNAs, followed by the production of various tsRNAs, especially Class I tsRNAs (tRF-1s). Through further screening, we show that tRF-Gln-CTG-026 (tG026), the optimal tRF-1, ameliorates liver injury by repressing global protein synthesis through the weakened association between TSR1 (pre-rRNA-processing protein TSR1 homolog) and pre-40S ribosome. This study indicates the potential of tsRNA-reduced global protein synthesis in liver injury and repair, suggesting a potential therapeutic strategy for liver injury.

Abstract Background The treatment of gastric cancer remains a challenge. Methods We divided gastric cancer into three subtypes based on 14 cancer functional states. We investigated differences between subtypes through multi-omics data, especially at the single-cell level, which allowed us to analyze differences from the perspective of each type of cell rather than the whole. Results The cluster 1 is characterized by high levels of tumor progression-related cancer functional status, worst survival outcomes, low metabolic level, high infiltration of immunosuppressive cells, high copy number variations (CNV), and low tumor mutational burden (TMB). The cluster 2 is characterized by low levels of tumor progression-related cancer functional status, favorable prognosis, moderate metabolic level, low immune cell infiltration, high CNV, and moderate TMB. Then, the cluster 3 is characterized by the high level of all cancer functional status, high metabolic level, low CNV, high TMB, high infiltration of immune cells with high cytotoxicity, and better response to immunotherapy. We also established a prognostic model based on cancer functional status and validated its robustness. Conclusions Collectively, our study identified gastric cancer subtypes and provided new insights into the clinical treatment of gastric cancer.

Abstract Hypoxia is one of the malignant characteristics of solid tumors and is related to the multiple malignant characteristics of the tumor. No study has not yet reported a systematical analysis of the characteristics of hypoxia from single-cell resolution in gastric cancer. In our research, we investigated the hypoxia features of various types of cells in single-cell resolution, identified hypoxia-related genes by the weighted gene co-expression network analysis method. Through the hypoxia-related genes from single-cell levels, we screened out 13 genes and established a prognostic model. This model performs well in the training dataset and multiple independent verification data sets. We thought that tumor hypoxia might affect the DNA methylation of cells and promote the transcription of genes associated with malignant features, thereby promoting tumor progression. We found that the more tumor associated genes in the high-risk group showed hypomethylation and high hypoxia-risk score group have more tumor-related genes, more immunosuppressive immune cells and more enrichment of cancer -related pathways. The lower risk group is more sensitive to three chemotherapy drugs for gastric cancer. Our study illustrates the crucial role of hypoxia in gastric cancer. Hypoxia-related gene prognostic model has been established and has good performance. Hypoxia-related risk score can also be used to guide a patient’s drug treatment strategy.

Objective The purpose of this scoping review was to synthesise the effectiveness and acceptability of decision aids for critically ill patients and family members in the intensive care unit (ICU).Methods A systematic search of four electronic databases and grey literature was undertaken to identify relevant studies on the application of decision aids in the ICU, without publication date restriction, through March 2023. The methodological framework proposed by Arksey and O’Malley was used to guide the scoping review.Results Fourteen papers were ultimately included in this review. However, only nine decision aids were available, and it is noteworthy that many of these studies focused on the iterative development and testing of individual decision aids. Among the included studies, 92% (n=13) were developed in North America, with a primary focus on goals of care and life-sustaining treatments. The summary of the effect of decision aid application revealed that the most common indicators were the level of knowledge and code status, and some promising signals disappeared in randomised trials.Conclusions The complexity of treatment decisions in the ICU exceeds the current capabilities of existing decision aids. There is a clear gap in decision aids that are tailored to different cultural contexts, highlighting the need to expand the scope of their application. In addition, rigorous quality control is very important for randomised controlled trial, and indicators for assessing the effectiveness of decision aids need to be further clarified.

Abstract Many resource-limited countries need an efficient and convenient method to assess disease progression in patients with coronavirus disease 2019 (COVID-19). This study developed and validated a complete blood count-based multivariate model for predicting the recovery of patients with moderate COVID-19. We collected the clinical data and laboratory test results of 86 patients with moderate COVID-19. These data were categorized into two subgroups depending on the laboratory test time. Univariate logistic regression and covariance diagnosis were used to screen for independent factors, and multifactorial logistic regression was used for model building. Data from 38 patients at another hospital were collected for external verification of the model. Basophils (OR 6.372; 95% CI 3.284–12.363), mean corpuscular volume (OR 1.244; 95% CI 1.088–1.422), red blood cell distribution width (OR 2.585; 95% CI 1.261–5.297), and platelet distribution width (OR 1.559; 95% CI 1.154–2.108) could be combined to predict recovery of patients with moderate COVID-19. The ROC curve showed that the model has good discrimination. The calibration curve showed that the model was well-fitted. The DCA showed that the model is clinically useful. Small increases in the above parameters within the normal range suggest an improvement in patients with moderate COVID-19.

Abstract Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism. We applied artificial intelligence to predict the protein structure of ELOVL2 and the interaction with its substrate. Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction, leading to key aging phenotypes at both cellular and physiological level. Furthermore, restoration of mitochondrial activity can rescue age-related macular degeneration (AMD) phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial (RPE) cells; this indicates a conservative mechanism in both human and mouse. Taken together, we revealed an epigenetic-metabolism axis contributing to aging and illustrate the power of an AI-based approach in structure-function studies.

Abstract Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, also known as Müllerian agenesis, is characterized by uterovaginal aplasia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Previous studies have associated sequence variants of PAX8, TBX6, GEN1, WNT4, WNT9B, BMP4, BMP7, HOXA10, EMX2, LHX1, GREB1L, LAMC1, and other genes with MRKH syndrome. The purpose of this study was to identify the novel genetic causes of MRKH syndrome. Ten patients with MRKH syndrome were recruited at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Whole-exome sequencing was performed for each patient. Sanger sequencing confirmed the potential causative genetic variants in each patient. In silico analysis and American College of Medical Genetics and Genomics (ACMG) guidelines helped to classify the pathogenicity of each variant. The Robetta online protein structure prediction tool determined whether the variants affected protein structures. Eleven variants were identified in 90% (9/10) of the patients and were considered a molecular genetic diagnosis of MRKH syndrome. These 11 variants were related to nine genes: TBC1D1, KMT2D, HOXD3, DLG5, GLI3, HIRA, GATA3, LIFR, and CLIP1. Sequence variants of TBC1D1 were found in two unrelated patients. All variants were heterozygous. These changes included one frameshift variant, one stop-codon variant, and nine missense variants. All identified variants were absent or rare in gnomAD East Asian populations. Two of the 11 variants (18.2%) were classified as pathogenic according to the ACMG guidelines, and the remaining nine (81.8%) were classified as variants of uncertain significance. Robetta online protein structure prediction analysis suggested that missense variants in TBC1D1 (p.E357Q), HOXD3 (p.P192R), and GLI3 (p.L299V) proteins caused significant structural changes compared to those in wild-type proteins, which in turn may lead to changes in protein function. This study identified many novel genes, especially TBC1D1, related to the pathogenesis of MRKH syndrome. The identification of these variants provides new insights into the etiology of MRKH syndrome and a new molecular genetic reference for the development of the reproductive tract.

The manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis. Previous work indicated that the MEIG1/PACRG complex locates in the manchette and is involved in the transport of cargos, such as SPAG16L, to build the sperm flagellum. Here, using co-immunoprecipitation and pull-down approaches in various cell systems, we established that DNALI1, an axonemal component originally cloned from Chlamydomonas reinhardtii, recruits and stabilizes PACRG and we confirm in vivo, the co-localization of DNALI1 and PACRG in the manchette by immunofluorescence of elongating murine spermatids. We next generated mice with a specific deficiency of DNALI1 in male germ cells, and observed a dramatic reduction of the sperm cells, which results in male infertility. In addition, we observed that the majority of the sperm cells exhibited abnormal morphology including misshapen heads, bent tails, enlarged midpiece, discontinuous accessory structure, emphasizing the importance of DNALI1 in sperm differentiation. Examination of testis histology confirmed impaired spermiogenesis in the mutant mice. Importantly, while testicular levels of MEIG1, PACRG, and SPAG16L proteins were unchanged in the Dnali1 mutant mice, their localization within the manchette was greatly affected, indicating that DNALI1 is required for the formation of the MEIG1/PACRG complex within the manchette. Interestingly, in contrast to MEIG1 and PACRG-deficient mice, the DNALI1-deficient mice also showed impaired sperm spermiation/individualization, suggesting additional functions beyond its involvement in the manchette structure. Overall, our work identifies DNALI1 as a protein required for sperm development.

Objective To investigate the relationship between sleep duration and activities of daily living (ADL) disability, and to explore the optimal sleep duration among oldest-old Chinese individuals. Methods In this cross-sectional study, 1,798 participants (73.2% female) were recruited from Dongxing and Shanglin in Guangxi Zhuang Autonomous Region, China in 2019. The restricted cubic spline function was used to assess the dose-response relationship between sleep duration and ADL disability, and the odds ratios (ORs) of the associations were estimated by logistic regression models. Results The overall prevalence of ADL disability was 63% (64% in females and 58% in males). The prevalence was 71% in the Han population (72% in females and 68% in males), 60% in the Zhuang population (62% in females and 54% in males) and 53% in other ethnic population (53% in females and 53% in males). A nonlinear relationship between sleep duration and ADL disability was observed. Sleep duration of 8-10 hours was associated with the lowest risk of ADL disability. Sleep duration (≥12 hours) was associated with the risk of ADL disability among the oldest-old individuals after adjusting for confounding factors (OR = 1.47, 95% CI [1.02, 2.10], p

Cone-rod dystrophy (CRD) is a genetically inherited retinal disease that can be associated with male infertility, while the specific genetic mechanisms are not well known. Here, we report CEP78 as a causative gene of a particular syndrome including CRD and male infertility with multiple morphological abnormalities of sperm flagella (MMAF) both in human and mouse. Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced ERG amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures. Cep78 deletion also caused male infertility and MMAF, with disordered ‘9+2’ structure and triplet microtubules in sperm flagella. Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. Furthermore, CEP78 regulated the interaction, stability, and centriolar localization of its interacting protein. Insufficiency of CEP78 or its interacting protein causes abnormal centriole elongation and cilia shortening. Absence of CEP78 protein in human caused similar phenotypes in vision and MMAF as Cep78−/− mice. Collectively, our study supports the important roles of CEP78 defects in centriole and ciliary dysfunctions and molecular pathogenesis of such multi-system syndrome.

Abstract Intrahepatic cholangiocarcinoma (CHOL) remains a rare malignancy, ranking as the leading lethal primary liver cancer worldwide. However, the biological functions of integrator complex subunit 8 (INTS8) in CHOL remain unknown. Thus, this research aimed to explore the potential role of INTS8 as a novel diagnostic or therapeutic target in CHOL. Differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO) datasets were obtained by the “RRA” package in R software. The “maftools” package was used to visualize the CHOL mutation data from The Cancer Genome Atlas (TCGA) database. The expression of INTS8 was detected by performing quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry in cell lines and human samples. The association between subtypes of tumour-infiltrating immune cells (TIICs) and INTS8 expression in CHOL was determined by using CIBERSORT tools. We evaluated the correlations between INTS8 expression and mismatch repair (MMR) genes and DNA methyltransferases (DNMTs) in pan-cancer analysis. Finally, the pan-cancer prognostic signature of INTS8 was identified by univariate analysis. We obtained the mutation landscapes of an RRA gene set in CHOL. The expression of INTS8 was upregulated in CHOL cell lines and human CHOL samples. Furthermore, INTS8 expression was closely associated with a distinct landscape of TIICs, MMR genes, and DNMTs in CHOL. In addition, the high INTS8 expression group presented significantly poor outcomes, including overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI) (p

BackgroundBullous pemphigoid (BP) is a rare autoimmune skin condition that causes large fluid-filled blisters on the skin, especially in older adults. BP has been linked to various diseases and medications, but its association with cognitive outcomes is unclear.MethodsWe conducted a systematic review and meta-analysis of studies investigating the association between BP and cognitive outcomes, such as all-cause dementia, Alzheimer's disease, and vascular dementia in middle-aged and older adults. We searched PubMed, Embase, and Web of Science databases for relevant studies published up to March 2023. We included studies that reported odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between BP and cognitive outcomes. We pooled the ORs, or HRs using random-effects models and performed subgroup and sensitivity analyses to explore potential sources of heterogeneity.ResultsThe study selection process identified 13 studies for inclusion in the analysis, 11 studied arms of which used a case-control design and 7 studied arms of which used a cohort design. The studies were conducted primarily in Europe, with a few from Asia and the United States. The meta-analysis found that BP was associated with higher odds of all-cause dementia in middle-aged and older participants in both cohort studies(HR = 1.41,95% CI: 1.20-1.66, P = 0.000) and case-control (OR = 4.25, 95% CI, 2.73-6.61; P = 0.000). The study found no significant publication bias in the included studies. The meta-regression analyses identified some subgroups associated with significantly reported odds ratios in case-control association analysis, including Europe, BP diagnosed based on clinical, histology, immunofluorescence, and both adjustment status of NO and YES.ConclusionsOur meta-analysis suggests that BP is associated with an increased risk of all-cause dementia in middle-aged and older adults. Further studies are needed to elucidate the underlying mechanisms and causal relationship between BP and cognitive outcomes.

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive dysfunction, but the results of individual studies have been inconsistent. This systematic review and meta-analysis aimed to evaluate the association between AD and cognitive dysfunction in middle-aged and older adults.MethodsTo find relevant research, a comprehensive search of electronic databases from the beginning to March 2023 was carried out. Data were taken from studies that were eligible, and a meta-analysis was done to determine the pooled hazard ratio (HR) and 95% confidence interval (CI).ResultsWe searched three databases and found a total of 15 studied arms included in 5 cohort studies with over 8.5 million participants were included in the analysis. The results showed that individuals with AD had a higher risk of developing dementia of all-cause dementia (pooled hazard ratio (HR) = 1.16; 95% CI, 1.10-1.23,PConclusionsIn conclusion, this study demonstrated that AD was associated with increased risk of cognitive dysfunction, particularly dementia of the Alzheimer type and all-cause dementia, in middle-aged and older participants. Further research is needed to understand the mechanisms behind this association and its potential implications for clinical practice.Systematic review registrationPROSPERO, identifier (CRD42023411627).

ObjectiveSurfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants MethodsMedical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE.ResultsTwenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate).ConclusionsCompared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation.

Objective To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas.Data source Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019.Study selection The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons.Data analysis The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model.Results 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2–0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (

Abstract. A close relationship has recently been described between subjective cognitive decline (SCD) and gut microbiota disorders. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with SCD. We conducted a study of 60 participants with SCD. Sixty participants were allocated to either EA group (n = 30) or sham acupuncture group (n = 30). Both groups received 24 sessions of real acupuncture treatment or identical treatment sessions using the placebo needle. Global cognitive change based on a comprehensive neuropsychological test battery was evaluated to detect the clinical efficacy of acupuncture treatment at the baseline and the end of treatment. Faecal microbial analyses were carried out after collecting stools at T0 and T12 weeks. Microbiomes were analyzed by 16S ribosomal RNA gene sequencing. Correlation analyses were performed to investigate the relationships between the changes in gut microbiota and symptom improvement. Age is a particularly important factor leading to the severity of dementia. Compared with sham acupuncture group, the number of Escherichia–Shigella in EA group decreased after treatment. The number of Escherichia–Shigella in EA group decreased after treatment compared with EA group before treatment. Bifidobacterium is positively correlated with clinical efficacy Z-score and Montreal Cognitive Assessment Scale (both P

Abstract. Background. Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC. Methods. We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses. Results. Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) (41.5%) and HR−/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR−/HER2− (19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2− and HR−/HER2− tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR−/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008). Conclusion. Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies. Trial registration. chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030

Abstract. Background:. Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. Methods:. Forty patients with both-column acetabular fractures were recruited in the randomized prospective case–control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, n = 20; conventional method group, n = 20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. Results:. The operation and instrumentation times in the 3D printing group were significantly shorter (130.8 ± 29.2 min, t = −7.5, P

Fuchs' endothelial corneal dystrophy (FECD) is a disease where progressive visual impairment occurs by the thickening of the Descemet's membrane and the gradual degeneration and loss of corneal endothelial cells. This study aimed to investigate the key changes in gene expression associated with FECD and explore potential biomarkers and new therapeutic strategies for FECD. To explore the potential therapeutic targets of FECD, we downloaded the gene expression dataset GSE171830 from the Gene Expression Omnibus (GEO) database. A total of 303 differentially expressed genes (DEGs) were identified by the limma package. The enriched Gene Ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included the extracellular matrix organization, collagen-containing extracellular matrix, and the structural constituents of the extracellular matrix. Fifteen hub genes from the most significant module were ascertained by Cytoscape. Both collagen-containing extracellular matrix and extracellular matrix hit to ANXA1, VCAN, GPC3, TNC, IGFBP7, MATN3, and SPARCL1 genes in the GO cellular components. Among these genes, the expression of SPARCL1 was down-regulated in the FECD samples, whereas the expression of GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 was up-regulated in the FECD samples. Gene set enrichment analysis (GSEA) plots showed that among the 20,937 genes, SPARCL1 played an important role in three pathways, cytokine-cytokine receptor interaction, the TGF-beta signaling pathway, and antigen processing and presentation. The top three pathways enriched by the GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 genes were those for cytokine-cytokine receptor interaction, TGF-beta signaling, and RIG-I-like receptor signaling. In conclusion, the DEGs identified here might assist clinicians in understanding the pathogenesis of FECD. Furthermore, these identified biomarkers might serve as potential therapeutic targets for the treatment of FECD.

Skin cutaneous melanoma (SKCM) is a common cancer of which mortality is increasing continuously. Our study conducted a series of analyses on the clinical significance of Serine/threonine kinase 17B (STK17B) in SKCM to provide a new biomarker for diagnosis and treatment. The RNA-sequence data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The data of 468 SKCM patients were divided into STK17B high- and low-expression groups and analyzed by Bioconductor package to identify the differential expressed genes. The R package of "clusterProfiler" was used for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene-Set Enrichment Analysis analyses. A protein-protein interaction network and immune infiltration landscape were respectively constructed via STRING database and ssGSEA. STK17B had lower expression in SKCM than normal tissues. Besides, STK17B expression was significantly related to some clinicopathological characteristics in SKCM patients including T stage, Breslow depth, radiation therapy, melanoma Clark level, and pathologic stage. The Kaplan-Meier curve analyses revealed that the low expression of STK17B was correlated with poor overall survival and disease-specific survival. We constructed nomograms to predict the 1-, 3-, and 5-year survival of SKCM patients. The function enrichment analyses showed STK17B-related differential expressed genes were enriched in cellular differentiation and immune-related progress. STK17B expression level were positively correlated with infiltrating level of immune cells. In this study, we found that STK17B, which played an important role in immune infiltration, could be a new biomarker for diagnosis and prognosis in SKCM patients.

Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I2 statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09–2.42], Phet = 0.377, Pz = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07–3.83], Phet = 0.085, Pz = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43–3.02], Phet

An effective traffic control strategy will improve travel reliability in urban transportation networks. Lack of coordination between vehicles, however, exacerbates congestion due mainly to frequent stops at unsignalized intersections. It is beneficial to develop a conflict-free cooperation method that collects basic safety message from multiple approaching Connected and Autonomous Vehicles (for short, CAVs) and guarantees efficient unsignalized intersection operations with safe and incident free vehicle maneuvers. This paper proposes an interspersed traffic organization method under controlled constraints. Firstly, relied on shared location technology and considered the operating characteristics of CAVs at unsignalized intersections to detect and analyze traffic conflicts to establish a right-of-way judgment model for CAVs. In order to further ensure the safety and operating efficiency of the vehicle, based on the judgment results of right-of-way judgment model, a vehicle speed guidance model is established for different traffic conditions. Taking the real city standard intersection as the experimental analysis object, through data collection and simulation experiment, the signal control method and the organization method proposed in this paper are compared and analyzed. The results showed that the traffic organization method proposed in this paper improves the operational efficiency of 46%, the average travel time is reduced by 6.54s, which is not only better than the signal control method, but also supports the development of car networking technology.

Background The functional significance of ADAMs family members in the immune infiltration of pancreatic adenocarcinoma (PAAD) awaits elucidation. Methods ADAMs family members with significant expression were identified among differentially expressed genes of PAAD based on The Cancer Genome Atlas (TCGA) database followed by a verification based on the Oncomine database. The correlation of ADAMs in PAAD was estimated with the Spearman’s rho value. The pathway enrichment of ADAMs was performed by STRING and GSEALite, respectively. The protein–protein interaction and Gene Ontology analyses of ADAMs and their similar genes were exanimated in STRING and visualized by Cytoscape. Subsequently, the Box-Whisker plot was used to show a correlation between ADAMs and different tumor grade 1/2/3/4 with Student’s t-test. TIMER was applied to estimate a correlation of ADAMs expressions with immune infiltrates and immune checkpoint blockade (ICB) immunotherapy-related molecules. Furthermore, the effect of copy number variation (CNV) of ADAMs genes was assessed on the immune infiltration levels. Result ADAM8/9/10/12/15/19/28/TS2/TS12 were over-expressed in PAAD. Most of the nine ADAMs had a significant correlation. ADAM8/12/15/19 expression was remarkably increased in the comparison between grade 1 and grade 2/3 of PAAD. ADAM8/9/10/12/19/28/TS2/TS12 had a positive correlation with almost five immune infiltrates. ADAM12/19/TS2/TS12 dramatically related with ICB immunotherapy-related molecules. CNV of ADAMs genes potentially influenced the immune infiltration levels. Conclusion Knowledge of the expression level of the ADAMs family could provide a reasonable strategy for improved immunotherapies to PAAD.