Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study.

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

Influence of microplastics on the availability of antibiotics in soils.

Microplastics (MPs) and antibiotics, as two major types of emerging pollutants, inevitably coexist in the soil environment due to agricultural film residue, sewage irrigation and sludge application. However, the impact of MPs on antibiotic availability in soils with varying characteristics has not been extensively studied. Therefore, in this study, an interference experiment was conducted using three types of MPs (polyethylene (PE), polyvinyl chloride (PVC) and polypropylene (PP)) in red soil, paddy soil and cinnamon soil. The available antibiotics in soils were evaluated using diffusive gradients in thin-films (DGT). Results showed that MPs had a significant impact on the amount of antibiotics adsorbed on soil solid (Cs) by providing additional binding sites or altering soil characteristics (e.g., pH and dissolved organic carbon). The most significant effects on Cs were observed in cinnamon soil, and the Cs values were dependent on concentration of MPs. The available antibiotics, as measured by DGT significantly decreased after the addition of MPs. This decrease was influenced by the soil characteristics. However, the concentration of antibiotics in soil solutions (Cd) was only slightly impacted by MPs. Therefore, the influence of MPs on the migration of antibiotics was reflected by their impact on the soil/water partition coefficient (Kd), while the resupply ability (R) from the soil solid phase was less influential. Moreover, the dosage of MPs had a significant effect on the availability of antibiotics in CS by promoting the adsorption of antibiotics on the solid phase, while in RS and PS, the soil properties played a dominate role in the changes in antibiotic availability after MP addition. These results indicate that the impact of MPs on available antibiotics mainly depends on soil properties. In addition, DGT measurement is more sensitive than soil solution to investigate the effects of coexisting pollutants on the behavior of antibiotics in soil.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study.

OBJECTIVES: Previous studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). METHODS: We conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. RESULTS: The results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016-1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (ß-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81-0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696-0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057-1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049-1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024-1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05-1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044-1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. CONCLUSIONS: This study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Network pharmacology combined with molecular docking and experimental validation to explore the potential mechanism of Cinnamomi ramulus against ankylosing spondylitis.

BACKGROUND: Cinnamomi ramulus (C. ramulus) is frequently employed in the treatment of ankylosing spondylitis (AS). However, the primary constituents, drug targets, and mechanisms of action remain unidentified. METHODS: In this study, various public databases and online tools were employed to gather information on the compounds of C. ramulus, drug targets, and disease targets associated with ankylosing spondylitis. The intersection of drug targets and disease targets was then determined to identify the common targets, which were subsequently used to construct a protein-protein interaction (PPI) network using the STRING database. Network analysis and the analysis of hub genes and major compounds were conducted using Cytoscape software. Furthermore, the Metascape platform was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking studies and immunohistochemical experiments were performed to validate the core targets. RESULTS: The network analysis identified 2-Methoxycinnamaldehyde, cinnamaldehyde, and 2-Hydroxycinnamaldehyde as the major effective compounds present in C. ramulus. The PPI network analysis revealed PTGS2, MMP9, and TLR4 as the most highly correlated targets. GO and KEGG analyses indicated that C. ramulus exerts its therapeutic effects in ankylosing spondylitis through various biological processes, including the response to hormones and peptides, oxidative stress response, and inflammatory response. The main signaling pathways involved were IL-17, TNF, NF-kappa B, and Toll-like receptor pathways. Molecular docking analysis confirmed the strong affinity between the key compounds and the core targets. Additionally, immunohistochemical analysis demonstrated an up-regulation of PTGS2, MMP9, and TLR4 levels in ankylosing spondylitis. CONCLUSIONS: This study provides insights into the effective compounds, core targets, and potential mechanisms of action of C. ramulus in the treatment of ankylosing spondylitis. These findings establish a solid groundwork for future fundamental research in this field.

To infer the probability of cervical ossification of the posterior longitudinal ligament and explore its impact on cervical surgery.

The ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is commonly observed in degenerative changes of the cervical spine. Early detection of cervical OPLL and prevention of postoperative complications are of utmost importance. We gathered data from 775 patients who underwent cervical spine surgery at the First Affiliated Hospital of Guangxi Medical University, collecting a total of 84 variables. Among these patients, 144 had cervical OPLL, while 631 did not. They were randomly divided into a training cohort and a validation cohort. Multiple machine learning (ML) methods were employed to screen the variables and ultimately develop a diagnostic model. Subsequently, we compared the postoperative outcomes of patients with positive and negative cervical OPLL. Initially, we compared the advantages and disadvantages of various ML methods. Seven variables, namely Age, Gender, OPLL, AST, UA, BMI, and CHD, exhibited significant differences and were used to construct a diagnostic nomogram model. The area under the curve (AUC) values of this model in the training and validation groups were 0.76 and 0.728, respectively. Our findings revealed that 69.2% of patients who underwent cervical OPLL surgery eventually required elective anterior surgery, in contrast to 86.8% of patients who did not have cervical OPLL. Patients with cervical OPLL had significantly longer operation times and higher postoperative drainage volumes compared to those without cervical OPLL. Interestingly, preoperative cervical OPLL patients demonstrated significant increases in mean UA, age, and BMI. Furthermore, 27.1% of patients with cervical anterior longitudinal ligament ossification (OALL) also exhibited cervical OPLL, whereas this occurrence was only observed in 6.9% of patients without cervical OALL. We developed a diagnostic model for cervical OPLL using the ML method. Our findings indicate that patients with cervical OPLL are more likely to undergo posterior cervical surgery, and they exhibit elevated UA levels, higher BMI, and increased age. The prevalence of cervical anterior longitudinal ligament ossification was also significantly higher among patients with cervical OPLL.

HDAC4 induces the development of asthma by increasing Slug-upregulated CXCL12 expression through KLF5 deacetylation.

BACKGROUND: Asthma is a frequently occurring respiratory disease with an increasing incidence around the world. Airway inflammation and remodeling are important contributors to the occurrence of asthma. We conducted this study aiming at exploring the effect of Histone deacetylase 4 (HDAC4)-mediated Kruppel-like factor 5 (KLF5)/Slug/CXC chemokine ligand-12 (CXCL12) axis on the development of asthma in regulation of airway inflammation and remodeling. METHODS: An asthmatic rat model was induced by ovalbumin (OVA) irrigation, and determined HDAC4, KLF5, Slug, and CXCL12 expression in the lung tissues by RT-qPCR and Western blot assay. OVA was also used to induce a cell model of asthma in human BEAS-2B and HBE135-E6E7bronchial epithelial cells. The airway hyperresponsiveness (AHR), and expression of inflammatory cytokines in model mice were examined using methacholine challenge test and ELISA. The biological behaviors were measured in asthma model bronchial smooth muscle cells (BSMCs) following loss- and gain- function approaches. The interactions between HDAC4, KLF5, Slug, and CXCL12 were also detected by IP assay, dual luciferase gene reporter assay, and ChIP. RESULTS: HDAC4 was upregulated in lung tissues of OVA-induced asthmatic mice, and inhibition of HDAC4 alleviated the airway inflammation and remodeling. HDAC4 increased KLF5 transcriptional activity through deacetylation; deacetylated KLF5 bound to the promoter of Slug and transcriptionally upregulated Slug expression, which in turn increased the expression of CXCL12 to promote the inflammation in bronchial epithelial cells and thus induce the proliferation and migration of BSMCs. CONCLUSION: Collectively, HDAC4 deacetylates KLF5 to upregulate Slug and CXCL12, thereby causing airway remodeling and facilitating progression of asthma.

BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3.

BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1), and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in the initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1ΔIEC, Mel18ΔIEC, DKO, and TKO mice). We also disrupted Bmi1 and/or Mel18 specifically in intestinal epithelial cells (IECs) using the villin-CreERT2-inducible promoter. CAC was induced in cre-negative littermate mice (control) and mice with conditional disruption of Bmi1 and/or Mel18 by intraperitoneal injection of azoxymethane (AOM) followed by addition of dextran sulfate sodium (DSS) to drinking water. Colon tissues were collected from mice and analyzed by histology and immunoblots; IECs were isolated and used in cDNA microarray analyses. RESULTS: Following administration of AOM and DSS, DKO mice developed significantly fewer polyps than control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice. Adenomas in the colons of DKO mice were low-grade dysplasias, whereas adenomas in control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice were high-grade dysplasias with aggressive invasion of the muscularis mucosa. Disruption of Bmi1 and Mel18 (DKO mice) during late stages of carcinogenesis significantly reduced the numbers of large adenomas and the load of total adenomas, reduced proliferation, and increased apoptosis in colon tissues. IECs isolated from DKO mice after AOM and DSS administration had increased expression of Reg3b compared with control, Bmi1ΔIEC, or Mel18ΔIEC mice. Expression of REG3B was sufficient to inhibit cytokine-induced activation of STAT3 in IECs. The human REG3ß protein, the functional counterpart of mouse REG3B, inhibited STAT3 activity in human 293T cells, and its expression level in colorectal tumors correlated inversely with pSTAT3 level and survival times of patients. CONCLUSIONS: BMI1 and MEL18 contribute to the development of CAC in mice by promoting proliferation and reducing apoptosis via suppressing expression of Reg3b. REG3B negatively regulates cytokine-induced activation of STAT3 in colon epithelial cells. This pathway might be targeted in patients with colitis to reduce carcinogenesis.

Monascustin, an Unusual γ-Lactam from Red Yeast Rice.

Monascustin (1), an unusual γ-lactam, was isolated from an ethanol extract of the Monascus purpureus fermented rice. Its structure including the absolute configuration was determined by spectroscopic data analysis and confirmed by X-ray crystallography. A plausible biosynthetic pathway is discussed on the basis of amino acid derivatization. Compound 1 showed inhibitory activity against histone deacetylase 1.

Four new taraxastane-type triterpenoic acids from Cirsium setosum.

Four new taraxastane-type triterpenoids acids 3ß,22α-dihydroxy-20-taraxasten-30-oic acid (1), 3ß-hydroxy-22-oxo-20-taraxasten-30-oic acid (2), 3-oxo-22α-hydroxy-20- taraxasten-30-oic acid (3), and 3ß,19ß-dihydroxy-20-taraxasten-30-oic acid (4) were isolated and characterized from Cirsium setosum (Willd.) MB. Their structures were determined by the combination of 1D and 2D NMR experiments ((1)H-(1)HCOSY, HSQC, HMBC and ROESY) and mass spectrometry. Compound 2 exhibited potent selective cytotoxicity against human ovarian cancer cell line A2780 with an IC50 value of 3.9 µM.