Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

Validation of Artificial Intelligence-based Bowel Preparation Assessment in Screening Colonoscopy.

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5mm adenomas, and should undergo an early repeat colonoscopy. In this study, we employed artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system in accurately identifying patients who are at high risk of missing >5mm adenoma due to inadequate bowel preparation. PATIENTS AND METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University from October 8, 2021, to November 9, 2022. Eligible patients underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using e-Boston Bowel Preparation Scale (BBPS) while endoscopists evaluated using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy, otherwise the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 ＞5mm adenomas were detected, while 27 ＞5mm adenomas were missed. In unqualified-AI patients, the >5mm AMR was significantly higher than in qualified-AI patients (35.71% vs 13.19%, p=0.0056, OR 0.2734, 95% CI 0.1139, 0.6565), as were the AMR (50.89% vs 20.79%, p<0.001, OR 0.2532, 95% CI 0.1583, 0.4052) and >5mm PMR (35.82% vs 19.48%, p=0.0152, OR 0.4335, 95% CI 0.2288, 0.8213). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI showed unacceptable >5mm AMR, provided key evidence for implementing AI in guiding the bowel re-cleansing, potentially standardizing the future colonoscopy screening; ClincialTrials.gov, NCT05145712.

WSA-MP-Net: Weak-signal-attention and multi-scale perception network for microvascular extraction in optical-resolution photoacoustic microcopy.

The unique advantage of optical-resolution photoacoustic microscopy (OR-PAM) is its ability to achieve high-resolution microvascular imaging without exogenous agents. This ability has excellent potential in the study of tissue microcirculation. However, tracing and monitoring microvascular morphology and hemodynamics in tissues is challenging because the segmentation of microvascular in OR-PAM images is complex due to the high density, structure complexity, and low contrast of vascular structures. Various microvasculature extraction techniques have been developed over the years but have many limitations: they cannot consider both thick and thin blood vessel segmentation simultaneously, they cannot address incompleteness and discontinuity in microvasculature, there is a lack of open-access datasets for DL-based algorithms. We have developed a novel segmentation approach to extract vascularity in OR-PAM images using a deep learning network incorporating a weak signal attention mechanism and multi-scale perception (WSA-MP-Net) model. The proposed WSA network focuses on weak and tiny vessels, while the MP module extracts features from different vessel sizes. In addition, Hessian-matrix enhancement is incorporated into the pre-and post-processing of the input and output data of the network to enhance vessel continuity. We constructed normal vessel (NV-ORPAM, 660 data pairs) and tumor vessel (TV-ORPAM, 1168 data pairs) datasets to verify the performance of the proposed method. We developed a semi-automatic annotation algorithm to obtain the ground truth for our network optimization. We applied our optimized model successfully to monitor glioma angiogenesis in mouse brains, thus demonstrating the feasibility and excellent generalization ability of our model. Compared to previous works, our proposed WSA-MP-Net extracts a significant number of microvascular while maintaining vessel continuity and signal fidelity. In quantitative analysis, the indicator values of our method improved by about 1.3% to 25.9%. We believe our proposed approach provides a promising way to extract a complete and continuous microvascular network of OR-PAM and enables its use in many microvascular-related biological studies and medical diagnoses.

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats.

BACKGROUND: Fractures heal through a process that involves angiogenesis and osteogenesis but may also lead to non-union or delayed healing. Bone marrow mesenchymal stem cells (BMSCs) have been reported to play a pivotal role in bone formation and vascular regeneration and the p75 neurotrophin receptor (p75NTR) as being an important regulator of osteogenesis. Herein, we aim to determine the potential mediation of BMSCs by p75NTR in bone healing. METHODS: Rat BMSCs were identified by flow cytometry (FCM) to detect cell cycle and surface markers. Then transfection of si/oe-p75NTR was performed in BMSCs, followed by Alizarin red staining to detect osteogenic differentiation of cells, immunofluorescence double staining was performed to detect the expression of p75NTR and sortilin, co-immunoprecipitation (CO-IP) was conducted to analyze the interaction between p75NTR and sortilin, and EdU staining and cell scratch assay to assess the proliferation and migration of human umbilical vein endothelial cells (HUVECs). The expression of HIF-1α, VEGF, and apoptosis-related proteins were also detected. In addition, a rat fracture healing model was constructed, and BMSCs-si-p75NTR were injected, following which the fracture condition was observed using micro-CT imaging, and the expression of platelet/endothelial cell adhesion molecule-1 (CD31) was assessed. RESULTS: The results showed that BMSCs were successfully isolated, p75NTR inhibited apoptosis and the osteogenic differentiation of BMSCs, while si-p75NTR led to a decrease in sortilin expression in BMSCs, increased proliferation and migration in HUVECs, and upregulation of HIF-1α and VEGF expression. In addition, an interaction was observed between p75NTR and sortilin. The knockdown of p75NTR was found to reduce the severity of fracture in rats and increase the expression of CD31 and osteogenesis-related proteins. CONCLUSION: Silencing p75NTR effectively modulates BMSCs to promote osteogenic differentiation and angiogenesis, offering a novel perspective for improving fracture healing.

Quantitative analysis of pyrolysis characteristics and chemical components of tobacco materials based on machine learning.

To investigate the quantitative relationship between the pyrolysis characteristics and chemical components of tobacco materials, various machine learning methods were used to establish a quantitative analysis model of tobacco. The model relates the thermal weight loss rate to 19 chemical components, and identifies the characteristic temperature intervals of the pyrolysis process that significantly relate to the chemical components. The results showed that: 1) Among various machine learning methods, partial least squares (PLS), support vector regression (SVR) and Gaussian process regression (GPR) demonstrated superior regression performance on thermogravimetric data and chemical components. 2) The PLS model showed the best performance on fitting and prediction effects, and has good generalization ability to predict the 19 chemical components. For most components, the determination coefficients R 2 are above 0.85. While the performance of SVR and GPR models was comparable, the R 2 for most chemical components were below 0.75. 3) The significant temperature intervals for various chemical components were different, and most of the affected temperature intervals were within 130°C-400°C. The results can provide a reference for the materials selection of cigarette and reveal the possible interactions of various chemical components of tobacco materials in the pyrolysis process.

Pars plana vitrectomy for retinal detachment using perfluoro-n-octane as intraoperative tamponade: a multicenter, randomized, non-inferiority trial.

AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.

A real-time deep learning-based system for colorectal polyp size estimation by white-light endoscopy: development and multicenter prospective validation.

BACKGROUND: The choice of polypectomy device and surveillance intervals for colorectal polyps are primarily decided by polyp size. We developed a deep learning-based system (ENDOANGEL-CPS) to estimate colorectal polyp size in real time. METHODS: ENDOANGEL-CPS calculates polyp size by estimating the distance from the endoscope lens to the polyp using the parameters of the lens. The depth estimator network was developed on 7297 images from five virtually produced colon videos and tested on 730 images from seven virtual colon videos. The performance of the system was first evaluated in nine videos of a simulated colon with polyps attached, then tested in 157 real-world prospective videos from three hospitals, with the outcomes compared with that of nine endoscopists over 69 videos. Inappropriate surveillance recommendations caused by incorrect estimation of polyp size were also analyzed. RESULTS: The relative error of depth estimation was 11.3% (SD 6.0%) in successive virtual colon images. The concordance correlation coefficients (CCCs) between system estimation and ground truth were 0.89 and 0.93 in images of a simulated colon and multicenter videos of 157 polyps. The mean CCC of ENDOANGEL-CPS surpassed all endoscopists (0.89 vs. 0.41 [SD 0.29]; P<0.001). The relative accuracy of ENDOANGEL-CPS was significantly higher than that of endoscopists (89.9% vs. 54.7%; P<0.001). Regarding inappropriate surveillance recommendations, the system's error rate is also lower than that of endoscopists (1.5% vs. 16.6%; P<0.001). CONCLUSIONS: ENDOANGEL-CPS could potentially improve the accuracy of colorectal polyp size measurements and size-based surveillance intervals.

Enhancing Diagnostic Accuracy for Gastric Cancer: Integration of Multi-Slice Spiral CT and Gastrointestinal Angiography.

Objective: This study aimed to assess the clinical efficacy of combining multi-slice spiral CT with gastrointestinal angiography for diagnosing gastric cancer. Methods: We conducted a retrospective analysis of clinical data from 151 patients with suspected gastric cancer admitted to our hospital between January 2014 and January 2022. Among them, 70 patients underwent multi-slice spiral CT alone (control group), while the remaining 81 patients underwent multi-slice spiral CT in combination with gastrointestinal barium contrast (combination group). Finally, pathological examination confirmed gastric cancer in 81 patients. We analyzed the diagnostic efficacy of multi-slice spiral CT combined with gastrointestinal angiography for staging gastric cancer and detecting lymph node metastasis. Results: The sensitivity and accuracy of diagnosing gastric cancer using multi-slice spiral CT combined with gastrointestinal angiography were significantly superior to CT alone (P < .05). This combined approach exhibited substantial advancements in detecting stage I and II tumors compared to a single CT, although the difference in stage III detection rate was marginal (P < .05). Furthermore, among the 81 gastric cancer cases, 67 were confirmed to have lymph node metastasis through surgical and pathological examination. The lymph node detection rate with multi-slice spiral CT combined with gastrointestinal angiography was significantly higher than that achieved with single CT (P < .05). Conclusions: Combining multi-slice spiral CT with gastrointestinal angiography proved to be an effective diagnostic strategy for gastric cancer.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Effect of artificial intelligence on novice-performed colonoscopy: a multicenter randomized controlled tandem study.

BACKGROUND AND AIMS: The efficacy and safety of colonoscopy performed by artificial intelligence (AI)-assisted novices remain unknown. The aim of this study was to compare the lesion detection capability of novices, AI-assisted novices, and experts. METHODS: This multicenter, randomized, noninferiority tandem study was conducted across 3 hospitals in China from May 1, 2022, to November 11, 2022. Eligible patients were randomized into 1 of 3 groups: the CN group (control novice group, withdrawal performed by a novice independently), the AN group (AI-assisted novice group, withdrawal performed by a novice with AI assistance), or the CE group (control expert group, withdrawal performed by an expert independently). Participants underwent a repeat colonoscopy conducted by an AI-assisted expert to evaluate the lesion miss rate and ensure lesion detection. The primary outcome was the adenoma miss rate (AMR). RESULTS: A total of 685 eligible patients were analyzed: 229 in the CN group, 227 in the AN group, and 229 in the CE group. Both AMR and polyp miss rate were lower in the AN group than in the CN group (18.82% vs 43.69% [P < .001] and 21.23% vs 35.38% [P < .001], respectively). The noninferiority margin was met between the AN and CE groups of both AMR and polyp miss rate (18.82% vs 26.97% [P = .202] and 21.23% vs 24.10% [P < .249]). CONCLUSIONS: AI-assisted colonoscopy lowered the AMR of novices, making them noninferior to experts. The withdrawal technique of new endoscopists can be enhanced by AI-assisted colonoscopy. (Clinical trial registration number: NCT05323279.).

miR-146a-5p Alleviates Radiation-Induced Liver Fibrosis by Regulating PTPRA-SRC Signaling in Mice.

Patients with hepatobiliary tumors who accept radiotherapy are at risk for radiation-induced liver fibrosis. MicroRNAs (miRNAs) have been implicated in the pathogenesis of radiation-induced liver damage and possess potential as novel biomarkers and therapeutic targets. However, the role of miR-146a-5p in radiation-induced liver fibrosis is less well understood. The current study was designed to evaluate the role of miR-146a-5p in radiation-induced liver fibrosis in mice and to investigate the possible mechanisms involved in miR-146a-5p-mediated effects. The experiments were performed on Institute of Cancer Research (ICR) mice which received fractionated radiation (30 Gy in 5 fractions) to the liver. The results show radiation could induce histopathological changes, liver dysfunction and fibrosis accompanied with decreased miR-146a-5p expression. miR-146a-5p agomir treatment resulted in recovery of liver function and reduced the amount of alpha-smooth muscle actin (α-SMA), collagen 1, protein tyrosine phosphatase receptor type A (PTPRA) and phosphorylated SRC in the livers of irradiated mice. Therefore, our study reveals that miR-146a-5p inhibits the progression of hepatic fibrosis after radiation treatment. And the beneficial role of miR-146a-5p may be relevant to PTPRA-SRC signaling pathway.

Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice.

In this study, we investigated the effects of Lactobacillus johnsonii on the mouse colitis model. The results showed that the supernatant of the L. johnsonii culture alleviated colitis and remodeled gut microbiota, represented by an increased abundance of bacteria producing short-chain fatty acids, leading to an increased concentration of propionic acid in the intestine. Further studies revealed that propionic acid inhibited activation of the MAPK signaling pathway and polarization of M1 macrophages. Macrophage clearance assays confirmed that macrophages are indispensable for alleviating colitis through propionic acid. In vitro experiments showed that propionic acid directly inhibited the MAPK signaling pathway in macrophages and reduced M1 macrophage polarization, thereby inhibiting the secretion of pro-inflammatory cytokines. These findings improve our understanding of how L. johnsonii attenuates inflammatory bowel disease (IBD) and provide valuable insights for identifying molecular targets for IBD treatment in the future.

Computed Tomography-Based Deep Learning Model for Assessing the Severity of Patients With Connective Tissue Disease-Associated Interstitial Lung Disease.

OBJECTIVES: This study aimed to develop a computed tomography (CT)-based deep learning model for assessing the severity of patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD). METHODS: The retrospective study included 298 CTD-ILD patients between January 2018 and May 2022. A deep learning-based RDNet model was established (1610 fully annotated CT images for training and 402 images for validation). The model was used to automatically classify and quantify 3 radiologic features (ground glass opacities [GGOs], reticulation, and honeycombing), along with a volumetric sum of 3 areas (ILD%). As a control, we used 4 previously defined CT threshold methods to calculate the ILD assessment index. The Spearman rank correlation coefficient ( r ) evaluated the correlation between various indicators and the lung function index in the remaining 184 CTD-ILD patients who were staged according to the gender-age-physiology (GAP) system. RESULTS: The RDNet model accurately identified GGOs, reticulation, and honeycombing, with corresponding Dice indexes of 0.784, 0.782, and 0.747, respectively. A total of 137 patients were at GAP1 (73.9%), 36 patients at GAP2 (19.6%), and 11 patients at GAP3 (6.0%). The percentages of reticulation and honeycombing at GAP2 and GAP3 were markedly elevated compared with those at GAP1 ( P < 0.001). The percentage of GGOs was not significantly different among the GAP stages ( P = 0.62). As the GAP stage increased, all lung function indicators tended to decrease, and the composite physiologic index (CPI) indicated an upward tendency. The percentage of honeycombs moderately correlated with the percentage of diffusing capacity of the lung for carbon monoxide (DLco%) ( r = -0.58, P < 0.001) and CPI ( r = 0.63, P < 0.001). The ILD assessment index calculated by the CT threshold method (-260 to -600 Hounsfield units) had a low correlation with DLco% and CPI (DLco%: r = -0.42, P < 0.001; CPI: r = 0.45, P < 0.001). CONCLUSIONS: The RDNet model can quantify GGOs, reticulation, and honeycombing of chest CT images in CTD-ILD patients, among which honeycombing had the most significant effect on lung function indicators. In addition, this model provided good clinical utility for evaluating the severity of CTD-ILD.

Development and Validation of a Deep Learning-Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions.

OBJECTIVES: The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)-based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. METHODS: The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. RESULTS: The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. CONCLUSIONS: This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models.

CircTUBD1 Regulates Radiation-induced Liver Fibrosis Response via a circTUBD1/micro-203a-3p/Smad3 Positive Feedback Loop.

Background and Aims: Radiation-induced liver fibrosis (RILF), delayed damage to the liver (post-irradiation) remains a major challenge for the radiotherapy of liver malignancies. This study investigated the potential function and mechanism of circTUBD1 in the development of RILF. Methods: By using a dual luciferase assay, RNA pull-down assays, RNA sequencing, chromatin immunoprecipitation (known as ChIP) assays, and a series of gain- or loss-of-function experiments, it was found that circTUBD1 regulated the activation and fibrosis response of LX-2 cells induced by irradiation via a circTUBD1/micro-203a-3p/Smad3 positive feedback loop in a 3D system. Results: Knockdown of circTUBD1 not only reduced the expression of α-SMA, as a marker of LX-2 cell activation, but also significantly decreased the levels of hepatic fibrosis molecules, collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and connective tissue growth factor (CTGF) in a three-dimensional (3D) culture system and RILF model in vivo. Notably, knockdown of circTUBD1 alleviated early liver fibrosis induced by irradiation in mice models. Conclusions: This study is the first to reveal the mechanism and role of circTUBD1 in RILF via a circTUBD1/micro-203a-3p/Smad3 feedback loop, which provides a novel therapeutic strategy for relieving the progression of RILF.

[Spatiotemporal charactersitics of decoupling between land surface thermal environment and ecosystem ser-vice value in Pearl River Delta Urban Agglomeration, China]. / ç ä¸‰è§’åŸŽå¸‚ç¾¤åœ°è¡¨çƒ­çŽ¯å¢ƒä¸Žç”Ÿæ€ç³»ç»ŸæœåŠ¡ä»·å€¼è§£è€¦çš„æ—¶ç©ºç‰¹å¾.

The Pearl River Delta Urban Agglomeration (PRDUA) is a highly urbanized region in China. The urbanized climate, especially the heat island effect, has a significant impact on urban ecosystems and habitats. Based on MODIS land surface temperature (LST) data and land cover data in 2000, 2005, 2010, 2015, and 2019, we quantified the land surface thermal environment and ecosystem service value (ESV), analyzed the decoupling between LST and ESV in the PRDUA from 2000 to 2019 using the decoupling analysis model, revealed the trade-off between them, and analyzed the spatiotemporal variation of the synergistic state between LST and ESV in PRDUA. The results showed that, from 2000 to 2019, the spatial pattern of land surface thermal environment in the PRDUA was relatively stable in time series but showed spatial variation with high fluctuation in the core area and low fluctuation in the peripheral area. The ESV of the PRDUA showed a trend of stable spatial distribution and decreasing in time series. The ESV of all the nine cities in PRDUA decreased by more than 9%. The decoupling between land surface thermal environment and the overall ESV of the PRDUA, as well as with the values of provisioning, regulating and support services, was dominated by weak negative decoupling and strong negative decoupling, showing a more significant trade-off, which indicated that the ecosystems of the PRDUA were still significantly influenced by the environmental characteristics of urbanization, and that the spatiotemporal variation of the decoupling states was related to the spatial variation of urbanization levels in PRDUA. The formulation of future ecological policies in the PRDUA must consider the differences in urbanization levels and the differences in the trade-offs between urbanized environments and ecosystems to precisely formulate ecological control and restoration plans and improve the efficiency and implementation effects of ecological planning.

Selection of dilution material for non-iodinated iodine as an oral contrast agent for esophageal cancer: a preliminary clinical trial.

PURPOSE: To investigate the filling state of the esophagus using different oral contrast agents for the diagnosis of esophageal cancer by computed tomography (CT). MATERIALS AND METHODS: This preliminary clinical trial enrolled patients with suspected esophageal carcinoma and admitted from January 2015 to January 2018. The patients were randomized into the yogurt (mixed with ioversol), lotus root powder (mixed with ioversol), gas-producing powder, and control (pure iodine water) groups. Chest CT examinations were performed. The degree of esophageal filling and the detection of esophageal lesions were compared. RESULTS: Finally, 136 participants were enrolled (n = 34/group). There were no significant differences in esophageal filling degree among the yogurt, lotus root powder, and gas-producing powder groups (P = 0.093). There were 30/3/1 and 30/3/1 confirmed/false-negative/false-positive diagnoses in the yogurt and lotus powder groups, respectively, compared with 28/5/1 and 25/8/1 in the gas-producing powder and control groups, respectively. The concordance rates were the highest for the yogurt (88.2%, with 91.7% specificity and 86.4% sensitivity) and lotus root powder groups (88.2%, with 92.3% specificity and 85.7% sensitivity) and the lowest for the control group (73.5%, with 90.0% specificity and 66.7% sensitivity). CONCLUSION: Yogurt mixed with ioversol could fill and expand the esophagus with minimal preparation, displaying the structure of the esophageal lumen and wall thickness. This mixture might be used as a positive contrast agent for esophageal CT. Similar results were observed for the lotus root powder mixed with ioversol, but its preparation was more arduous.

Application Value of Gastroenterography Combined With CT in the Evaluation of Short-Term Efficacy and Prognosis in Patients With Esophageal Cancer Radiotherapy.

Purpose: To observe the application value of gastroenterography combined with CT in the evaluation of short-term efficacy and prognosis in patients with esophageal cancer radiotherapy. Methods: From January 2013 to December 2020, the clinical data of 207 patients with esophageal cancer treated by radiotherapy in our hospital were collected retrospectively. All patients received gastroenterography and CT examination before and after radiotherapy, and the patients were followed-up for 1 year, and the evaluation value of their short-term efficacy and prognosis was observed. Results: After radiotherapy, the length diameter, short diameter, and volume of the lymph node were lower than those before radiotherapy (p < 0.05), but the maximum tube wall thickness had no significant difference (p > 0.05). The length diameter, short diameter, and volume of the lymph node, and the maximum tube wall thickness in the good efficacy group and the good prognosis group were lower, and the objective response rate in the good prognosis group was higher (p < 0.05). The area under the curve (AUC) of the length diameter, short diameter, and volume of the lymph node to evaluate the short-term efficacy of patients with esophageal cancer was 0.738, 0.705, and 0.748, respectively, and the AUC to evaluate the prognosis of patients with esophageal cancer was 0.751, 0.776, and 0.791, respectively. Conclusion: Gastroenterography combined with CT has a good application value in the evaluation of short-term efficacy and prognosis in patients with esophageal cancer radiotherapy.

How Nanotechniques Could Vitalize the O-GlcNAcylation-Targeting Approach for Cancer Therapy.

Accumulated data indicated that many types of cancers have increased protein O-GlcNAcylation at cell surface and inside cells. The aberrant O-GlcNAcylation is considered a potential therapeutic target. Although several types of compounds capable of inhibiting O-GlcNAcylation have been developed, their low solubility, poor permeability and delivery efficiency have impeded the application for in vivo and pre-clinical studies. Nanocarriers have the advantages of controllable drug release and active cancer-targeting capability. Moreover, nanoparticles can improve drug delivery efficiency and reduce the non-specific distribution in normal tissues by the enhanced permeability and retention (EPR) effect in cancer. Taking the advantage of O-GlcNAc-specific antibodies or lectins, nanoparticles could further improve their cancer-targeting capability. Although nanocarriers targeting the canonical N- and O-linked glycosylation have been extensively investigated for cancer detection and therapy, application of nanotechniques for the specific targeting of O-GlcNAcylation has not been actively pursued. This review summarizes the general features of GlcNAcylation and its alterations in cancers. Analyses are focused on the following areas: How the nanocarriers may improve the solubility and/or cell permeability of O-GlcNAc transferase (OGT) inhibitors; The modification of nanocarriers with lectins or antibodies for active targeting of O-GlcNAc; The nanocarriers-mediated co-delivery of OGT inhibitors and conventional drugs, which may lead to synergistic effects. Unsolved issues impeding the research progression on O-GlcNAcylation-targeting scheme are also discussed.

Protein profiling of hemolymph in Haemaphysalis flava ticks.

BACKGROUND: Tick hemolymph bathes internal organs, acts as an exchange medium for nutrients and cellular metabolites, and offers protection against pathogens. Hemolymph is abundant in proteins. However, there has been limited integrated protein analysis in tick hemolymph thus far. Moreover, there are difficulties in differentiating tick-derived proteins from the host source. The aim of this study was to profile the tick/host protein components in the hemolymph of Haemaphysalis flava. METHODS: Hemolymph from adult engorged H. flava females was collected by leg amputation from the Erinaceus europaeus host. Hemolymph proteins were extracted by a filter-aided sample preparation protocol, digested by trypsin, and assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). MS raw data were searched against the UniProt Erinaceidae database and H. flava protein database for host- and tick-derived protein identification. Protein abundance was further quantified by intensity-based absolute quantification (iBAQ). RESULTS: Proteins extracted from hemolymph unevenly varied in size with intense bands between 100 and 130 kDa. In total, 312 proteins were identified in the present study. Therein 40 proteins were identified to be host-derived proteins, of which 18 were high-confidence proteins. Top 10 abundant host-derived proteins included hemoglobin subunit-α and subunit-ß, albumin, serotransferrin-like, ubiquitin-like, haptoglobin, α-1-antitrypsin-like protein, histone H2B, apolipoprotein A-I, and C3-ß. In contrast, 169 were high-confidence tick-derived proteins. These proteins were classified into six categories based on reported functions in ticks, i.e., enzymes, enzyme inhibitors, transporters, immune-related proteins, muscle proteins, and heat shock proteins. The abundance of Vg, microplusin and α-2-macroglobulin was the highest among tick-derived proteins as indicated by iBAQ. CONCLUSIONS: Numerous tick- and host-derived proteins were identified in hemolymph. The protein profile of H. flava hemolymph revealed a sophisticated protein system in the physiological processes of anticoagulation, digestion of blood meal, and innate immunity. More investigations are needed to characterize tick-derived proteins in hemolymph.