Severity Identification of Graves Orbitopathy via Random Forest Algorithm.

This study aims to establish a random forest model for detecting the severity of Graves Orbitopathy (GO) and identify significant classification factors. This is a hospital-based study of 199 patients with GO that were collected between December 2019 and February 2022. Clinical information was collected from medical records. The severity of GO can be categorized as mild, moderate-to-severe, and sight-threatening GO based on guidelines of the European Group on Graves' orbitopathy. A random forest model was constructed according to the risk factors of GO and the main ocular symptoms of patients to differentiate mild GO from severe GO and finally was compared with logistic regression analysis, Support Vector Machine (SVM), and Naive Bayes. A random forest model with 15 variables was constructed. Blurred vision, disease course, thyroid-stimulating hormone receptor antibodies, and age ranked high both in mini-decreased gini and mini decrease accuracy. The accuracy, positive predictive value, negative predictive value, and the F1 Score of the random forest model are 0.83, 0.82, 0.86, and 0.82, respectively. Compared to the three other models, our random forest model showed a more reliable performance based on AUC (0.85 vs. 0.83 vs. 0.80 vs. 0.76) and accuracy (0.83 vs. 0.78 vs. 0.77 vs. 0.70). In conclusion, this study shows the potential for applying a random forest model as a complementary tool to differentiate GO severity.

Protocol for identifying stressed granulocytes from septic mice.

Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

The Mediating Role of Self-efficacy and Coping Mode Between Powerlessness and Quality of Life in Patients with Venous Leg Ulcers.

OBJECTIVE: To explore the mediating effect of self-efficacy and coping mode between powerlessness and quality of life in patients with a venous leg ulcer (VLU). METHODS: The authors used a convenience sampling method to select 208 patients with a VLU in four tertiary grade A hospitals in Qingdao and Tianjin from June 2021 to August 2022. Instruments included the Powerlessness Assessment Tool, Venous Leg Ulcer Self-efficacy Tool, Medical Coping Modes Questionnaire, and Venous Leg Ulcer Quality of Life Questionnaire. The authors used descriptive statistics, Pearson correlation, and PROCESS macros for data analysis. RESULTS: The powerlessness score was significantly negatively associated with self-efficacy and confrontation coping mode scores and positively associated with patients' quality-of-life scores. In addition, self-efficacy and confrontation coping modes separately and sequentially mediated the relationship between powerlessness and quality of life. CONCLUSIONS: Self-efficacy and confrontation coping mode play important mediating roles between powerlessness and quality of life in patients with VLUs. By decreasing patients' sense of powerlessness, boosting their self-efficacy, and encouraging them to adopt confrontation coping mode, health professionals can improve patients' quality of life.

Effect of the time interval between denudation and ICSI on fresh embryo transfer reproductive outcomes: a retrospective study.

Purpose: This study aims to determine if the incubation after oocyte denudation before Intra-cytoplasmic sperm injection (ICSI) affects the clinical pregnancy rate. Methods: This was a retrospective, consecutive data analysis of 1370 patients who underwent ICSI cycles at the Department of Reproductive Medicine of West China Second University of Sichuan University (Chengdu, Sichuan) between January 2020 and July 2022. The primary outcome was the clinical pregnancy rate. The second outcome included fertilization rate, biochemical pregnancy rate, and miscarriage rates. Results: A total of 1370 continuous fresh transferred ICSI cycles were analyzed. Multivariate linear regression and logistic regression analysis of factors related to clinical pregnancy rates revealed that clinical pregnancy rates were significantly associated with denudation (DEN)-ICSI time interval. Long DEN-ICSI intervals are associated with a higher clinical pregnancy rate during fresh embryo transfer. Conclusion: The DEN-ICSI time interval is an independent factor for clinical outcomes in fresh ICSI transfer cycles.

Self-Adaptive Aromatic Cation-π Driven Dimensional Polymorphism in Supramolecular Polymers for the Photocatalytic Oxidation and Separation of Aromatic/Cyclic Aliphatic Compounds.

The phenomenon of polymorphism is ubiquitous in nature, the controlled manipulation of which not only increases our ontological understanding of nature but also facilitates the conceptualization and realization of novel functional materials. However, achieving targeted polymorphism in supramolecular assemblies (SAs) remains a formidable challenge, largely because of the constraints inherent in controlling the specific binding motifs of noncovalent interactions. Herein, we propose self-adaptive aromatic cation-π binding motifs to construct polymorphic SAs in both the solid and solution states. Using distinct discrete cation-π-cation and long-range cation-π binding motifs enables control of the self-assembly directionality of a C2h-symmetric bifunctional monomer, resulting in the successful formation of both two-dimensional and three-dimensional crystalline SAs (2D-CSA and 3D-CSA). The differences in the molecular packing of 3D-CSA compared with that of 2D-CSA significantly improve the charge separation and carrier mobility, leading to enhanced photocatalytic activity for the aerobic oxidation of thioanisole to methyl phenyl sulfoxide (yield of 99 % vs 57 %). 2D-CSA, which has a vertical extended structure with favorable stronger interaction with toluene though face-to-face cation-π interactions than methylcyclohexane, shows higher toluene/methylcyclohexane separation efficiency than 3D-CSA (96.9 % for 2D-CSA vs 56.3 % for 3D-CSA).

Causal relationships between Sjögren's syndrome and Parkinson's disease: A Mendelian randomization study.

BACKGROUND: Epidemiological and observational studies have indicated an association between Sjögren's syndrome (SS) and Parkinson's disease (PD). However, consistent conclusions have not been reached due to various limitations. In order to determine whether SS and PD are causally related, we conducted a Mendelian randomization study (MR) with two samples. METHODS: Data for SS derived from the FinnGen consortium's R9 release (2495 cases and 365 533 controls). Moreover, data for PD were acquired from the publicly available GWAS of European ancestry, which involved 33 674 cases and 449 056 controls. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between SS and PD. To assess the estimation's robustness, a number of sensitivity studies were performed. To determine the probability of reverse causality, we performed a reverse MR analysis. RESULTS: There was no evidence of a significant causal effect of SS on PD risks based on the MR [odds ratio (OR) = 1.03; 95% confidence interval (CI) = 0.95-1.11; p = .45]. Similarly, no evidence supported the causal effects of PD on SS (OR = 0.92; 95% CI = 0.81-1.04; p = .20). These findings held up under rigorous sensitivity analysis. CONCLUSIONS: MR bidirectional analysis did not reveal any cause-and-effect relationship between SS and PD, or vice versa. Further study of the mechanisms that may underlie the probable causal association between SS and PD is needed.

The role of the transcriptional repressor CssR in Corynebacterium glutamicum in response to phenolic compounds.

The cssR gene (ncgl1578) of Corynebacterium glutamicum encodes a repressor of the TetR (tetracycline regulator) family. Its role in the stress response to antibiotics/heavy metals has been investigated, but how CssR functions in response to phenolic compounds in C. glutamicum has been rarely studied. In this study, we applied transcriptomic analysis, ß-galactosidase analysis, qRT-PCR, and EMSAs to analyze the target genes and functions of CssR in response to phenolic compounds. Consistent with the upregulation of genes involved in the degradation of phenolic compounds, the ΔcssR mutant was more resistant to various phenolic compounds than was the wild-type strain. Furthermore, the addition of phenolic compounds induced the expression of corresponding genes (ncgl0283, ncgl1032, ncgl1111, ncgl2920, ncgl2923, and ncgl2952) in vivo. However, the DNA binding activity of CssR to the promoter of phenolic compound-degrading genes was undetected in vitro. Additionally, we also found that CssR indirectly negatively regulates the expression of cell wall/membrane/envelope biogenesis-related genes, which may enhance resistance to stress caused by phenolic compounds. Together, our findings demonstrate that CssR is a key regulator that copes with stress conditions induced by phenolic compounds, thus greatly expanding our understanding of the functions of TetR family transcription factors.

dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing.

Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized extracellular matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD206+ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

A method of quantitative chemiluminescence immunoassay for the concentration of Growth differentiation factor-15.

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor (TGF-ß) superfamily, and is expressed and secreted in response to inflammation, oxidative stress and hypoxia. It has been shown in several studies to be a predictor of heart failure. However, the only kits available on the market are ELISA kits, which are costly and error-prone and are not conducive for clinical use. Here, we developed a chemiluminescence kit which optimized the reaction conditions and the reaction time was reduced to 10 min. We further proved that it can be used to measure GDF-15 in serum or plasma accurately and fastly, and provide additional information for the diagnosis of heart failure disease. Methodological comparison and clinical study verified this method is a reliable, economical and highly automated blood test method.•All necessary steps and the reagents needed are provided.•Reliability of the chemiluminescence immunoassay was verified by analyzing serum GDF-15 levels from different groups.•GDF-15 can provide clinicians with reliable prediction and disease assessment of heart failure.

Periodic Lamellae-Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis.

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, we developed a highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) by surface-directed epitaxial crystallization. Our in vitro results showed that the PLN could precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhanced the migration and osteogenic differentiation of BMSCs. Notably, results suggested that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicated that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. Our findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis. This article is protected by copyright. All rights reserved.

Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Characteristics of bacterial community in eyelashes of patients with Demodex blepharitis.

BACKGROUND: Demodex blepharitis (DB) is a common disease of the ocular surface. The characteristics of the bacterial community in eyelash roots after Demodex infestation are still unknown. Knowledge of the characteristics of the bacterial community of eyelash follicles in patients with DB can provide valuable insights for guiding the diagnosis and treatment of DB. METHODS: Twenty-five patients with DB (DB group) and 21 non-DB volunteers (control group) were enrolled in the study. Eyelashes from the upper eyelid of the right eye were sampled, and 16S ribosomal DNA (rDNA) sequencing was performed to determine the V3-V4 regions of the microbial 16S rDNA gene within 1 month of infestation. The sequencing data of the two groups were analyzed and compared. The effect of the bacterium Burkholderia on the survival of Demodex mites was evaluated using Demodex obtained from 12 patients with DB other that the patients in the DB group. RESULTS: A total of 31 phyla and 862 genera were identified in the DB and control groups. The five most abundant phyla in the two groups were Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and Cyanobacteria. The abundance of Actinomycetes was significantly higher in the DB group than in the control group. At the genus level, the five most abundant genera in the two groups were Pseudomonas, Burkholderia-Caballeronia-Paraburkholderia, Rolstonia and Acinetobacter; Clostridium sensu stricto 1 was abundant in the control group and Corynebacterium_1 was abundant in the DB group. Compared with the control group, the abundance of Burkholderia-Caballeronia-Paraburkholderia was 2.36-fold lower in the DB group. Linear discriminant analysis Effect Size (LEfSe) analysis revealed Burkholderia-Caballeronia-Paraburkholderia, SC_I_84_unclassified, Nonmyxobacteria and Succinvibrio to be the major biomarkers in the control group and Catenibacterium and Lachnospiraceae NK4A136 group to be the major biomarkers in the DB group. To explore the performance of these optimal marker models, receiver operational characteristic curve analysis was performed, and the average area under the curve value of Burkholderia-Caballeronia-Paraburkholderia was 0.7448. Burkholderia cepacia isolated from normal human eyelashes was fermented, and the Demodex mites isolated from patient eyelashes were cultured together with its fermented supernatant. The results showed that the fermentation supernatant could significantly reduce the survival time of the Demodex mites, suggesting the potential therapeutic value of this bacterium against Demodex. CONCLUSIONS: The composition of the bacterial community in the eyelashes of DB patients differed from that in eyelashes of healthy volunteers, revealing a decrease in bacterial diversity in infested eyelashes. This decrease may be related to the occurrence and development of DB. The supernatant of Burkholderia cepacia culture medium was found to inhibit the growth of Demodex in eyelash hair follicles, providing a new insight with potential applications for the clinical treatment of Demodex infestation.

Stepwise self-inflating hydrogel expansion for congenital anophthalmia and blind microphthalmia: Over 15 years' experience in China.

BACKGROUND: Self-inflating hydrogel expanders have been used to treat anophthalmia and blind microphthalmia. This study aimed to investigate the long-term outcomes of treatment with self-inflating hydrogel expanders for congenital anophthalmia and blind microphthalmia. METHODS: In this retrospective study, the medical records of 161 patients with anophthalmia and blind microphthalmia who underwent hydrogel expansion were reviewed. We measured the palpebral fissure height (PFH), palpebral fissure length (PFL), and distance between the inner canthal and mid-nasal line (ICMN) before and after surgery. Cox regression analysis was conducted to determine which variables were related to the implantation of spherical expanders following hemispherical expander implantation. RESULTS: After treatment, the PFH and PFL increased significantly (p < 0.001). Complications including expander migration and extrusion occurred in 15 cases. Five patients needed enucleation or further dermis fat graft implantation because of insufficient expansion. The necessity for further spherical expansion was substantially related to a relative axial length (rAL) <0.5 (p = 0.007). CONCLUSION: Self-inflating hydrogel expansion can significantly increase the lid fissure. The occurrence of complications is rare, and surgical intervention can effectively address them. Abnormal eyes with a rAL of less than 0.5 demonstrate a higher possibility of needing additional orbital expansion.

A Review of deep learning methods for denoising of medical low-dose CT images.

To prevent patients from being exposed to excess of radiation in CT imaging, the most common solution is to decrease the radiation dose by reducing the X-ray, and thus the quality of the resulting low-dose CT images (LDCT) is degraded, as evidenced by more noise and streaking artifacts. Therefore, it is important to maintain high quality CT image while effectively reducing radiation dose. In recent years, with the rapid development of deep learning technology, deep learning-based LDCT denoising methods have become quite popular because of their data-driven and high-performance features to achieve excellent denoising results. However, to our knowledge, no relevant article has so far comprehensively introduced and reviewed advanced deep learning denoising methods such as Transformer structures in LDCT denoising tasks. Therefore, based on the literatures related to LDCT image denoising published from year 2016-2023, and in particular from 2020 to 2023, this study presents a systematic survey of current situation, and challenges and future research directions in LDCT image denoising field. Four types of denoising networks are classified according to the network structure: CNN-based, Encoder-Decoder-based, GAN-based, and Transformer-based denoising networks, and each type of denoising network is described and summarized from the perspectives of structural features and denoising performances. Representative deep-learning denoising methods for LDCT are experimentally compared and analyzed. The study results show that CNN-based denoising methods capture image details efficiently through multi-level convolution operation, demonstrating superior denoising effects and adaptivity. Encoder-decoder networks with MSE loss, achieve outstanding results in objective metrics. GANs based methods, employing innovative generators and discriminators, obtain denoised images that exhibit perceptually a closeness to NDCT. Transformer-based methods have potential for improving denoising performances due to their powerful capability in capturing global information. Challenges and opportunities for deep learning based LDCT denoising are analyzed, and future directions are also presented.

Visualization of therapeutic intervention for acute liver injury using low-intensity pulsed ultrasound-responsive phase variant nanoparticles.

Acute liver injury (ALI) is a highly fatal condition characterized by sudden massive necrosis of liver cells, inflammation, and impaired coagulation function. Currently, the primary clinical approach for managing ALI involves symptom management based on the underlying causes. The association between excessive reactive oxygen species originating from macrophages and acute liver injury is noteworthy. Therefore, we designed a novel nanoscale phase variant contrast agent, denoted as PFP@CeO2@Lips, which effectively scavenges reactive oxygen species, and enables visualization through low intensity pulsed ultrasound activation. The efficacy of the nanoparticles in scavenging excess reactive oxygen species from RAW264.7 and protective AML12 cells has been demonstrated through in vitro and in vivo experiments. Additionally, these nanoparticles have shown a protective effect against LPS/D-GalN attack in C57BL/6J mice. Furthermore, when exposed to LIPUS irritation, the nanoparticles undergo liquid-gas phase transition and enable ultrasound imaging.

Study of the mechanism underlying the anti-inflammatory effect of Miao medicine comprising raw and processed Radix Wikstroemia indica using the "sweat soaking method".

ETHNOPHARMACOLOGICAL RELEVANCE: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI). AIM OF THE STUDY: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method." MATERIALS AND METHODS: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. RESULTS: Eleven key anti-inflammatory targets of IL6, IL-1ß, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. CONCLUSIONS: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI.