Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer.

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Causal relationship between body mass index and anal fistula: a two-sample Mendelian randomization study.

Background: Significant evidence has been documented regarding the intricate connection between the development of anal fistula (AF) and the composition of Body Mass Index (BMI). Nevertheless, due to the inherent limitations of reverse causality and confounders inherent in observational studies, this relationship remains unclarified. Our study aims to reveal the causal impact between BMI and AF, as well as identify its associated risk factors, thereby providing a more comprehensive understanding of this complex interaction. Methods: Single nucleotide polymorphisms (SNPs) identified through genome-wide association study (GWAS) databases were used as instrumental variables for analysis. BMI served as the exposure variable, with six pooled GWAS datasets included. AF was the outcome variable. The Inverse Variance Weighted (IVW) method was used as the primary analytical technique, with MR-Egger regression, Weighted Median (WME) estimation, and Multiplicity Residual Sum and Outlier (MR-PRESSO) tests serving as secondary validations of the IVW results. Odds ratios (OR) were utilized as indicators to evaluate the causal relationship between BMI and AF. Results: A total of 738 SNPs strongly associated with the exposure were identified as instrumental variables. The IVW results demonstrated a positive correlation between BMI and the risk of AF. The MR-Egger analysis yielded p-values greater than 0.05, indicating no pleiotropic effects among the selected SNPs. Cochran's Q test also resulted in p-values greater than 0.05, suggesting no significant heterogeneity among the instrumental variables. The MR-PRESSO analysis revealed no horizontal pleiotropy or outliers potentially violating the causal assumption (p > 0.05). Conclusion: High BMI is positively associated with the risk of AF, and correcting BMI levels may have a preventive effect on the incidence of AF.

Non-soluble antibacterial polyurethane based on cation mechanism and functionalized by chitosan and heparin azide.

Nowadays, medical polyurethanes with favorable and durable antibacterial properties received more attention, because of avoiding repeated replacement of interventional materials and reducing patients' pain. In this thesis, non-soluble antibacterial polyurethane (NAPU) based on cation antibacterial mechanism was prepared by photo-grafting chitosan azide and heparin azide into polyurethane (PU). -NH3+of chitosan azide absorbed bacteria, inhibiting and breaking their mobility and structures. Heparin azide prevented cations from penetrating bacteria's membranes and inhibited their growth. The results showed that chitosan azide and heparin azide were successfully grafted into PU. The highest antibacterial rate was 92.07%, cytotoxicity grade ranging from 0-1 (RGR standard) and water contact angle exhibiting 60°, attributing to cation antibacterial effect and -OH existing. Tensile strength was up to 23.91 MPa and was suitable for using as medical materials. NAPU with long-lasting coating both possessed antibacterial properties and persistence, which can solve the problem of medical catheters' long-term using.

Epidemiology and distribution of 207 rare diseases in China: A systematic literature review.

Epidemiological data on rare diseases in China are currently limited. The objective of this study was to provide a comprehensive understanding of the prevalence and incidence of rare diseases by systematically analyzing the available epidemiological data. We conducted a comprehensive search of English and Chinese databases, the Incidence and Prevalence Database, the Chinese Rare Disease Guideline, and the Taiwan Health Promotion Administration from 2010 to 2023. We identified the top diseases and regions based on epidemiological data and present the maximum, minimum, and median prevalence and incidence values in tables and forest plots. 1,264 prevalence and incidence data were retrieved from 277 studies, guidelines and official websites, covering 110 rare diseases (53.1%) and 32 regions (94.1%). In terms of geographical regions, incidence or prevalence data were available for 32 regions (94.1%), excluding Tibet Hui Autonomous Region and Macao Special Administrative Region. In terms of rate, 60 and 77 out of 207 diseases (29.0% and 37.2%) had available incidence and prevalence data, respectively. Eight diseases had an incidence rate equal to or greater than that of 1,000 patients per million. The present study provides a comprehensive epidemiological analysis and valuable insights into the prevalence and incidence of rare diseases in China. Our findings underscore the pressing need for sustained drug research and medical support for individuals and families impacted by rare diseases.

Prevalence and risk factors of postoperative delirium in tumor patients after free flap reconstruction: A systematic review and meta-analysis of case-control studies.

BACKGROUND: Postoperative delirium is a severe complication of flap transplantation surgery, adversely affecting surgical prognoses. The intricate pathophysiology of postoperative delirium renders the elucidation of its risk factors challenging. This research aims to delineate the prevalence and the specific risk factors of postoperative delirium in patients with cancer undergoing free flap reconstruction through a systematic review and meta-analysis to enlighten proactive prevention measures. METHODS: The researchers systematically queried both the international and Chinese databases. Searches were performed for publications from inception until September 14, 2023, using the terms "free tissue flaps," "delirium," "neoplasms," and "risk factors." Data synthesis and statistical analysis were conducted using Stata SE (version 15.0) to calculate the combined effect size for identified risk factors. Reported outcomes included weighted mean differences or odds ratios with their respective 95% confidence intervals. RESULTS: Twelve case-control studies were included (ntotal = 3,256). Among them, 515 patients developed postoperative delirium after free flap surgery, compared with 2,741 patients who did not. The outcomes suggest that the risk factors include but are not limited to age, male, late neoplasm staging, use of hypnotic or antipsychotic, history of background diseases, psychiatric review, tracheotomy, and impaired wound healing. In contrast, early neoplasm staging and others are the protective factors with statistical significance. Multivariate analysis further identified significant correlations between preoperative albumin, perioperative blood transfusion, sleep disturbance, postoperative visual analog scale, postoperative albumin, smoking, and the appearance of postoperative delirium. CONCLUSION: The determined risk factors were grouped into preoperative, intraoperative, and postoperative categories substantiated by current data to present instructions for postoperative delirium prevention.

Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.

MAGPIE: accurate pathogenic prediction for multiple variant types using machine learning approach.

Identifying pathogenic variants from the vast majority of nucleotide variation remains a challenge. We present a method named Multimodal Annotation Generated Pathogenic Impact Evaluator (MAGPIE) that predicts the pathogenicity of multi-type variants. MAGPIE uses the ClinVar dataset for training and demonstrates superior performance in both the independent test set and multiple orthogonal validation datasets, accurately predicting variant pathogenicity. Notably, MAGPIE performs best in predicting the pathogenicity of rare variants and highly imbalanced datasets. Overall, results underline the robustness of MAGPIE as a valuable tool for predicting pathogenicity in various types of human genome variations. MAGPIE is available at https://github.com/shenlab-genomics/magpie .

Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling.

It is challenging to detect and differentiate multiple diseases with high complexity/similarity from the same organ. Metabolic analysis based on nanomatrix-assisted laser desorption/ionization mass spectrometry (NMALDI-MS) is a promising platform for disease diagnosis, while the enhanced property of its core nanomatrix materials has plenty of room for improvement. Herein, a multidimensional interactive cascade nanochip composed of iron oxide nanoparticles (FeNPs)/MXene/gold nanoparticles (AuNPs), IMG, is reported for serum metabolic profiling to achieve high-throughput detection of multiple liver diseases. MXene serves as a multi-binding site and an electron-hole source for ionization during NMALDI-MS analysis. Introduction of AuNPs with surface plasmon resonance (SPR) properties facilitates surface charge accumulation and rapid energy conversion. FeNPs are integrated into the MXene/Au nanocomposite to sharply reduce the thermal conductivity of the nanochip with negligible heat loss for strong thermally-driven desorption, and construct a multi-interaction proton transport pathway with MXene and AuNPs for strong ionization. Analysis of these enhanced serum fingerprint signals detected from the IMG nanochip through a neural network model results in differentiation of multiple liver diseases via a single pass and revelation of potential metabolic biomarkers. The promising method can rapidly and accurately screen various liver diseases, thus allowing timely treatment of liver diseases.

Application of 3D printing in ear reconstruction with autogenous costal cartilage: A systematic review.

PURPOSE: In recent years, 3D printing technology has been employed as a production method that builds materials layer upon layer, providing notable advantages in terms of individual customization and production efficiency. Autologous costal cartilage ear reconstruction has seen substantial changes due to 3D printing technology. In this context, this research evaluated the prospects and applications of 3D printing in ear reconstruction education, preoperative planning and simulation, the production of intraoperative guide plates, and other related areas. METHODOLOGY: All articles eligible for consideration were sourced through a comprehensive search of PubMed, the Cochrane Library, EMBASE, and Web of Science from inception to May 22, 2023. Two reviewers extracted data on the manufacturing process and interventions. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the research. Database searching yielded 283 records, of which 24 articles were selected for qualitative analysis. RESULTS: The utilization of 3D printing is becoming increasingly widespread in autogenous costal cartilage ear reconstruction, from education to the application of preoperative design and intraoperative guide plates production, possessing a substantial influence on surgical training, the enhancement of surgical effects, complications reduction, and so forth. CONCLUSION: This study sought to determine the application value and further development potential of 3D printing in autologous costal cartilage ear reconstruction. However, there is a lack of conclusive evidence on its effectiveness when compared to conventional strategies because of the limited number of cohort studies and randomized controlled trials. Simultaneously, the evaluation of the effect lacks objective and quantitative evaluation criteria, with most of them being emotional sentiments and ratings, making it difficult to execute a quantitative synthetic analysis. It is hoped that more large-scale comparative studies will be undertaken, and an objective and standard effect evaluation system will be implemented in the future.

A novel electrospun nanofiber system with PEGylated paclitaxel nanocrystals enhancing the transmucus permeability and in situ retention for an efficient cervicovaginal cancer therapy.

Overcoming the vaginal barrier to achieve sufficient drug penetration and retention is a huge obstacle for drug delivery in chemotherapeutics for cervical cancer. In this study, we investigate the feasibility of a novel composite nanocrystal/nanofiber system for improving the transmucus penetration and, thus, enhancing retention and drug delivery to the lesion of a cervicovaginal tumor. Herein, paclitaxel (PTX) was sequentially formulated in the form of nanocrystals, coated with polydopamine (PDA), and modified with PEG. The nanocrystals (NCs@PDA-PEG) were creatively fabricated to create a composite nanofibrous membrane (NCs@PDA-PEG NFs) by using an electrospinning technique. The morphology, size distribution, drug loading, encapsulation efficiency, X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectra, in vitro release, in vivo vaginal retention, apoptosis index, anti-tumor efficacy in a murine cervicovaginal tumor model, and local irritation were characterized. The NCs@PDA-PEG were formulated in a cube-like shape with an average size of 385.6 ± 35.47 nm; they were dispersed in electrospun nanofibers, and the drug loading was 7.94 %. The XRD curves indicated that the phase state of PTX changed after the creation of the nanocrystals. The FTIR spectra showed that the drug and the excipients were compatible with each other. In vitro delivery showed that the dissolution of PTX in the electrospun nanofibers was significantly faster than that when using bulk PTX. Compared with the PTX NC NFs, the NC@PDA-PEG NFs exhibited prolonged vaginal residence, superior transmucus penetration, minimal mucosal irritation, and significant tumor inhibition efficacy after the intravaginal administration of the NFs in tumor-bearing mice. In conclusion, by acting as novel pharmaceutical repositories, NCs@PDA-PEG NFs can be promising candidates for non-invasive local treatment, leading to efficient tumor inhibition in cervicovaginal cancer.

Polyurethane Foam Skeleton-Based Phase Change Hydrogel for Efficient Battery Thermal Management with Favorable Antivibration Performance.

Efficient thermal management is critical to ensure the safe and reliable operation of lithium-ion batteries (LIBs) as they are highly sensitive to temperature changes. Meanwhile, LIBs are exposed to various external forces during operation, such as vibration, shock, and oscillation, which may disrupt the physical and chemical processes inside the battery and lead to a decreased performance and shortened life. Here, we designed a phase change hydrogel (PCH) pad based on the polyurethane (PU) foam skeleton and demonstrated its effectiveness in efficient thermal management and improving antivibration performance. The thermal conductivity of the prepared composite is 0.65 W/(m·K), while the thermal contact resistance could decrease to ∼20 K·cm2/W under 60 °C. It exhibits a flexible contact transformation during the phase transition, resulting in enhanced interfacial heat transfer and storage rate, as well as improved resistance against external impacts. The temperature of the battery module wrapped with a composite plate decreases by 11.4 °C during the 6C discharge. Moreover, the additional heat generated by external vibration is only half that of the bare battery, and the temperature difference could reach 5.2 °C, demonstrating the effective buffering effect of PCH@PU in mitigating long-term discharge-induced increases in internal resistance. The developed PCH@PU, known for its exceptional thermal management and favorable antivibration performance, holds promising potential for widespread utilization in the field of power battery heat dissipation.

Genome Mining of Linaridins Provides Insights into the Widely Distributed LinC Oxidoreductases.

Linaridins are a family of underexplored ribosomally synthesized and post-translationally modified peptides despite the prevalence of their biosynthetic gene clusters (BGCs) in microbial genomes, as shown by bioinformatic studies. Our genome mining efforts reveal that 96 putative oxidoreductase genes, namely, LinC, are encoded in linaridin BGCs. We heterologously expressed two such LinC-containing linaridin BGCs, yan and ydn, from Streptomyces yunnanensis and obtained three new linaridins, named yunnanaridins A-C (1-3). Their structures are characterized by Z-configurations of the dehydrobutyrines and the presence of a variety of epimerized amino acid residues. Yunnanaridin A (1) is the sixth member of the family of type-B linaridins, whereas yunnanaridins B (2) and C (3) represent the first examples of expressed type-C linaridins. Interestingly, heterologous expression of the same BGCs with LinC in-frame knockouts produced the same compounds. This work expands the structural diversity of linaridins and provides evidence for the notion that the widespread LinCs may not be involved in linaridin biosynthesis.

The Clinical Efficacy Evaluation of Thigh Liposuction Based on 3-Dimensional Digital Technology: A Quantitative Study.

BACKGROUND: There is a lack of convenient and accurate objective methods to evaluate the clinical efficacy of thigh liposuction. METHODS: This retrospective study involved the 3-dimensional images of 19 patients who underwent bilateral thigh liposuction. Data such as volume change and volume change rate before and after surgery, circumference change, and circumference change rate of 3 planes (upper, middle, and lower) were analyzed. The correlation between body mass index and volume change rate and between preoperative circumference and circumference change rate of different planes were determined. RESULTS: There were significant differences between the preoperative and postoperative volume and circumference of 3 planes of 19 patients (38 thighs). The rate of change in total volume (16.90 ± 5.55%) correlated with the circumference change rate at the top of the thigh. There was also a linear relationship between body mass index and volume change rate, but not between preoperative circumference and circumference change rate. CONCLUSIONS: Three-dimensional imaging technology can accurately quantify the volume and circumference change of the thigh to objectively evaluate the clinical efficacy of thigh liposuction.

Deep Double Incomplete Multi-View Multi-Label Learning With Incomplete Labels and Missing Views.

View missing and label missing are two challenging problems in the applications of multi-view multi-label classification scenery. In the past years, many efforts have been made to address the incomplete multi-view learning or incomplete multi-label learning problem. However, few works can simultaneously handle the challenging case with both the incomplete issues. In this article, we propose a new incomplete multi-view multi-label learning network to address this challenging issue. The proposed method is composed of four major parts: view-specific deep feature extraction network, weighted representation fusion module, classification module, and view-specific deep decoder network. By, respectively, integrating the view missing information and label missing information into the weighted fusion module and classification module, the proposed method can effectively reduce the negative influence caused by two such incomplete issues and sufficiently explore the available data and label information to obtain the most discriminative feature extractor and classifier. Furthermore, our method can be trained in both supervised and semi-supervised manners, which has important implications for flexible deployment. Experimental results on five benchmarks in supervised and semi-supervised cases demonstrate that the proposed method can greatly enhance the classification performance on the difficult incomplete multi-view multi-label classification tasks with missing labels and missing views.

Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head.

OBJECTIVES: In the field of orthopedics, osteonecrosis of the femoral head (ONFH) is a common and refractory condition sometimes known as "immortal cancer" due to its complicated etiology, difficult treatment, and high disability rate. This paper's main goal is to examine the most recent literature on the pro-apoptotic effects of traditional Chinese medicine TCM monomers or compounds on osteocytes and to provide a summary of the potential signal routes. METHODS: The last ten years' worth of literature on ONFH as well as the anti-ONFH effects of aqueous extracts and monomers from traditional Chinese medicine were compiled. CONCLUSIONS: When all the relevant signal pathways are considered, the key apoptotic routes include those mediated by the mitochondrial pathway, the MAPK signaling pathway, the PI3K/Akt signaling pathway, the Wnt/-catenin signaling pathway, the HIF-1 signaling network, etc. As a result, we anticipate that this study will shed light on the value of TCM and its constituent parts for treating ONFH by inducing apoptosis in osteocytes and offer some guidance for the future development of innovative medications as anti-ONFH medications in clinical settings.

Safety Helmet Detection Based on YOLOv5 Driven by Super-Resolution Reconstruction.

High-resolution image transmission is required in safety helmet detection problems in the construction industry, which makes it difficult for existing image detection methods to achieve high-speed detection. To overcome this problem, a novel super-resolution (SR) reconstruction module is designed to improve the resolution of images before the detection module. In the super-resolution reconstruction module, the multichannel attention mechanism module is used to improve the breadth of feature capture. Furthermore, a novel CSP (Cross Stage Partial) module of YOLO (You Only Look Once) v5 is presented to reduce information loss and gradient confusion. Experiments are performed to validate the proposed algorithm. The PSNR (peak signal-to-noise ratio) of the proposed module is 29.420, and the SSIM (structural similarity) reaches 0.855. These results show that the proposed model works well for safety helmet detection in construction industries.

Potential Mechanisms Between HF and COPD: New Insights From Bioinformatics.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are closely related in clinical practice. This study aimed to investigate the co-genetic characteristics and potential molecular mechanisms of HF and COPD. HF and COPD datasets were downloaded from gene expression omnibus database. After identifying common differentially expressed genes (DEGs), the functional analysis highlighted the critical role of extracellular matrix and ribosomal signaling pathways in both diseases. In addition, GeneMANIA's results suggested that the 2 diseases were related to immune infiltration, and CIBERSORT suggested the role of macrophages. We also discovered 4 TFs and 1408 miRNAs linked to both diseases, and salbutamol may positively affect them.

Finite-time and fixed-time stabilization of multiple memristive neural networks with nonlinear coupling.

This brief presents the finite-time stabilization and fixed-time stabilization of multiple memristor-based neural networks (MMNNs) with nonlinear coupling. Under the retarded memristive theory, the generalized Lyapunov functional method, extended Filippov-framework and Laplacian matrix theory, we can realize both the finite-time stabilization and fixed-time stabilization problem of MMNNs by designing novel state-feedback controller and the corresponding adaptive controller with regulate parameters. Moreover, we assess the bounds of settling time for the both two kinds of stabilization respectively, and we deeply analyze the influence of initial desiring values and the linear growth condition of the controller on the system. Finally, the benefits of the proposed approach and the experimental analysis are demonstrated by numerical examples.

Function of Perceived Corporate Social Responsibility in Safety of Sports Activities and Home Aerobic Equipment in the Late Period of COVID-19.

The pandemic has impacted various industries, including the sports industry. However, corporate social responsibility (CSR) can mitigate the adverse effects of the crisis and promote the sports industry. To analyze the effect of CSR, the study examined the impact of perceived corporate social responsibility on injury prevention expectation, injury risk perception, and health up-gradation with the mediation of sports safety measures. There are 259 sportsmen of local sports bodies provided the data through a self-administered survey. Data analysis was conducted through Smart-PLS and SEM techniques. The outcome of the analysis showed that perceived corporate social responsibility leads to injury prevention expectation, injury risk perception, and health up-gradation. Also, the study found that sports safety measure mediates the relationship between perceived corporate social responsibility and injury prevention expectation, between perceived corporate social responsibility and injury risk perception, and between perceived corporate social responsibility and health up-gradation among sportsmen of local sports bodies. The theoretical implications were presented related to the significance of CSR and sports safety measure and their impact on sportsmen injury prevention expectation, health, and risk perception. The practical implications were related to the management of local sports bodies and how they can induce CSR initiatives and programs. Some limitations related to sample size, incorporating other variables, examining the model in other contexts, and using different study designs, have also been mentioned in the study.