Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth.

Glioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing the creatine transporter (SLC6A8). We hypothesized that TAMCs provide creatine to tumors, promoting GBM progression. Isotopic tracing demonstrated that TAMC-secreted creatine is taken up by tumor cells. Creatine supplementation protected tumors from hypoxia-induced stress, which was abrogated with genetic ablation or pharmacologic inhibition of SLC6A8. Lastly, inhibition of creatine transport using the clinically relevant compound, RGX-202-01, blunted tumor growth and enhanced radiation therapy in vivo. This work highlights that myeloid-to-tumor transfer of creatine promotes tumor growth in the hypoxic niche.

STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma.

As a key component of the standard of care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation of CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. We show that the engager B-LNPs block CD47 and PD-L1 and promote TAMC phagocytic activity. To enhance subsequent T cell recruitment and antitumor responses after tumor engulfment, the B-LNP was encapsulated with diABZI, a non-nucleotidyl agonist for stimulator of interferon genes. In vivo treatment with diABZI-loaded B-LNPs induced a transcriptomic and metabolic switch in TAMCs, turning these immunosuppressive cells into antitumor effectors, which induced T cell infiltration and activation in brain tumors. In preclinical murine models, B-LNP/diABZI administration synergized with radiotherapy to promote brain tumor regression and induce immunological memory against glioma. In summary, our study describes a nanotechnology-based approach that hijacks irradiation-triggered immune checkpoint molecules to boost potent and long-lasting antitumor immunity against glioblastoma.

High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules.

PURPOSE: To explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules. PATIENTS AND METHODS: A total of 550 patients with fine-needle aspiration (FNA)-evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, on the basis of which a diagnostic grading model for thyroid nodules was developed. The model was retrospectively trained on 124 postsurgical thyroid samples, optimized on 32 presurgical FNA samples, and prospectively validated on 394 presurgical FNA samples. Blinded central review-based cytopathologic and histopathologic diagnoses were used as the reference standard. RESULTS: For thyroid malignancy, the QCIGISH test achieved an overall diagnostic sensitivity of 100% (277/277), a specificity of 91.5% (107/117; 95% CI, 86.4 to 96.5), a positive predictive value (PPV) of 96.5% (95% CI, 94.4 to 98.6), and a negative predictive value (NPV) of 100% in the prospective validation, with a diagnostic accuracy of 97.5% (384/394; 95% CI, 95.9 to 99.0). QCIGISH demonstrated a PPV of 97.8% (95% CI, 94.7 to 100) and NPV of 100%, with a diagnostic accuracy of 98.2% (111/113; 95% CI, 95.8 to 100), for indeterminate Bethesda III-V thyroid nodules. QCIGISH demonstrated a PPV of 96.6% (95% CI, 91.9 to 100) and a NPV of 100%, with a diagnostic accuracy of 97.5% (79/81; 95% CI, 94.2 to 100), for Bethesda III-IV. For Bethesda VI, QCIGISH showed a 100% (184/184) accuracy. CONCLUSION: This imprinting biomarker-based test can effectively distinguish malignant from benign thyroid nodules. The high PPV and NPV make the test both an excellent rule-in and rule-out diagnostic tool. With such a diagnostic performance and its technical simplicity, this novel thyroid molecular test is clinically widely applicable.

The CXCL16-CXCR6 axis in glioblastoma modulates T-cell activity in a spatiotemporal context.

Introduction: Glioblastoma multiforme (GBM) pathobiology is characterized by its significant induction of immunosuppression within the tumor microenvironment, predominantly mediated by immunosuppressive tumor-associated myeloid cells (TAMCs). Myeloid cells play a pivotal role in shaping the GBM microenvironment and influencing immune responses, with direct interactions with effector immune cells critically impacting these processes. Methods: Our study investigates the role of the CXCR6/CXCL16 axis in T-cell myeloid interactions within GBM tissues. We examined the surface expression of CXCL16, revealing its limitation to TAMCs, while microglia release CXCL16 as a cytokine. The study explores how these distinct expression patterns affect T-cell engagement, focusing on the consequences for T-cell function within the tumor environment. Additionally, we assessed the significance of CXCR6 expression in T-cell activation and the initial migration to tumor tissues. Results: Our data demonstrates that CXCL16 surface expression on TAMCs results in predominant T-cell engagement with these cells, leading to impaired T-cell function within the tumor environment. Conversely, our findings highlight the essential role of CXCR6 expression in facilitating T-cell activation and initial migration to tumor tissues. The CXCL16-CXCR6 axis exhibits dualistic characteristics, facilitating the early stages of the T-cell immune response and promoting T-cell infiltration into tumors. However, once inside the tumor, this axis contributes to immunosuppression. Discussion: The dual nature of the CXCL16-CXCR6 axis underscores its potential as a therapeutic target in GBM. However, our results emphasize the importance of carefully considering the timing and context of intervention. While targeting this axis holds promise in combating GBM, the complex interplay between TAMCs, microglia, and T cells suggests that intervention strategies need to be tailored to optimize the balance between promoting antitumor immunity and preventing immunosuppression within the dynamic tumor microenvironment.

Ultrasound-based computer-aided diagnosis for cytologically indeterminate thyroid nodules with different radiologists.

PURPOSE: To evaluate a computer-aided diagnosis (CAD) technique in predicting malignancy for cytologically indeterminate thyroid nodules (TNs) as compared with different experienced radiologists. METHOD: 436 patients with 436 cytologically indeterminate TNs on fine-needle aspiration cytology (FNAC) were included and all were confirmed by surgical pathology. They were retrospectively analyzed with respect to ultrasound (US) characteristics using a commercially available CAD system (AmCAD-UT; AmCad BioMed, Taiwan, China) and reviewed by one junior and one senior radiologists.The CAD system and different experienced radiologists stratified the risk of malignancy using ACR TI-RADS category. The diagnostic performance by different experienced radiologists independently and after consulting the CAD (different experienced radiologists + CAD) and by the CAD alone were compared. RESULTS: The different experienced radiologists showed significantly higher specificities than the CAD system alone. The combination of radiologist and CAD system showed improved diagnostic performance with an AUC (Area under the curve) of 0.740 in the senior radiologist and 0.677 in the junior radiologist, as compared with CAD (AUC: 0.585) alone (all P < 0.05). The combination of senior radiologist and CAD system had the highest diagnostic performance (AUC: 0.740) and specificity (68.9%) compared to the others (all P < 0.05). CONCLUSION: The CAD system may play the potential role as a decision-making assistant alongside radiologists for differential diagnosis of TNs with indeterminate cytology.

Clinical Observation of the Effects of Oral Opioid on Inflammatory Cytokines and Gut Microbiota in Patients with Moderate to Severe Cancer Pain: A Retrospective Cohort Study.

INTRODUCTION: Recent studies have revealed that inflammation is a key factor in the causation of opioid analgesic tolerance. Opioids can induce a massive release of inflammatory cytokines and disruption of intestinal barrier function by activating Toll-like receptors 2/4 (TLR2/4), eventually resulting to sustained bacterial transmission and persistent systemic inflammation. However, most of the relevant analyses available were conducted at the level of animal experiments. It is necessary to explore the potential association between opioid tolerance and inflammatory cytokines and gut microbiota in patients with cancer pain. METHODS: We retrospectively analyzed cytokines, lymphocyte subsets and blood cells in 186 cancer patients to examine the effect of oral opioids on inflammatory cytokines in patients with moderate to severe cancer pain. The control group constituted tumor patients without cancer pain, while patients with moderate to severe cancer pain taking oral opioids made up the observation group. Fecal samples collected from 25 cancer patients were also analyzed for the composition and diversity of gut microbiota using 16S rRNA sequencing to explore the association between oral opioids and dynamic changes in gut microbiota. RESULTS: Patients with moderate to severe cancer pain taking oxycodone had significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ than those in the control group (p < 0.001). The difference in the relative abundance of Lactobacillus (p = 0.025), Anaerostipes (p = 0.034), Megamonas (p = 0.0080), Monoglobus (p = 0.0080), and the Rikenellaceae_RC9_gut_group (p = 0.022) between the opioid and control group was significant. CONCLUSION: Oral oxycodone can cause abnormal changes in cytokine levels and gut microbiota of patients with moderate to severe cancer pain, prompting chronic systemic inflammation. Analgesic tolerance induced by long-term oxycodone use could be closely related to the consistent upregulation of IL-6 and TNF-α levels.

Silencing ATF4 inhibits JMJD3-dependent JUNB/ETS1 axis and mitigates cerebral ischemic injury.

Activating transcription factor 4 (ATF4) is known to play an important role in cerebral ischemia through apoptosis and neuron regulation. Histone demethylase JMJD3, specifically removing the methylation of H3K27me3, is highlighted to attenuate cerebral ischemic injury. However, few studies have explored the interaction between ATF4 and JMJD3 in this disease. Thus, we intended to explore the effect of ATF4 on cerebral ischemia. We first constructed a mouse model of middle cerebral artery occlusion (MCAO) and cultured PC12 cells. Specifically, the regulatory function of ATF4 and demethylase JMJD3 on the ischemic injury was explored via using ectopic expression and depletion by determination of modified neurologic severity score, blood-brain barrier, brain water content, apoptosis, infarct size, oxidative stress, and inflammation. Moreover, the interaction among ATF4, JUNB, JMJD3, and ETS1 was assessed by western blot analysis, immunofluorescence, immunoprecipitation, and dual-luciferase reporter gene assay. These data showed that ATF4 and JMJD3 were upregulated in the MCAO model and PC12 cells. In addition, ectopic expression of ATF4 aggravated the ischemic injury through demethylation of JMJD3. Meanwhile, JMJD3 upregulated JUNB expression by inhibiting H3K21me2/3 enrichment and promoted ETS1 expression as well. Altogether, ATF4 could exacerbate cerebral ischemic injury through JMJD3-dependent upregulation of JUNB/ETS1 expression, suggesting a potential theoretical basis of treatment for cerebral ischemic injury.

Vision-Based Defect Inspection and Condition Assessment for Sewer Pipes: A Comprehensive Survey.

Due to the advantages of economics, safety, and efficiency, vision-based analysis techniques have recently gained conspicuous advancements, enabling them to be extensively applied for autonomous constructions. Although numerous studies regarding the defect inspection and condition assessment in underground sewer pipelines have presently emerged, we still lack a thorough and comprehensive survey of the latest developments. This survey presents a systematical taxonomy of diverse sewer inspection algorithms, which are sorted into three categories that include defect classification, defect detection, and defect segmentation. After reviewing the related sewer defect inspection studies for the past 22 years, the main research trends are organized and discussed in detail according to the proposed technical taxonomy. In addition, different datasets and the evaluation metrics used in the cited literature are described and explained. Furthermore, the performances of the state-of-the-art methods are reported from the aspects of processing accuracy and speed.

Genetic and Clinical Factors Associated with Opioid Response in Chinese Han Patients with Cancer Pain: An Exploratory Cross-Sectional Study.

INTRODUCTION: Studies have shown that genetic variation and environmental factors are associated with individual differences in therapeutic efficacy and side effects of opioids. However, the focus of these studies has been on a single factor of single-nucleotide polymorphisms (SNPs) or haplotypes, for which results have rarely been validated. For complex traits, such as cancer pain and opioid response, interactions between multiple genetic variation and environmental factors need to be considered to explain the opioid individual differences. METHODS: We conducted an exploratory two-stage cross-sectional study with 1027 Chinese patients who were taking strong opioid medications for their cancer pain, and genotyped 110 SNPs to explore the association of SNPs, haplotypes, gene-gene and gene-environment interactions with opioid dose, pain relief, and opioid-induced constipation. RESULTS: Due to the failure to meet Benjamini-Hochberg criteria in the discovery stage or to be validated in replication stage, no association was found between SNPs, haplotypes, paired SNP-SNP interactions or multi-dimensional gene-gene interactions and opioid response. However, for gene-environment interactions, optimal models have been constructed in all phenotypes of opioid response. CONCLUSIONS: This study reveals for the first time that construction of multidimensional gene-environment interactions enables better interpretations of the effect of genetic variation and environmental factors on the opioid response in patients with cancer pain. TRIAL REGISTRATION: Chictr.org.cn, identifier, ChiCTR2000033576.

Overexpression of ORX or MCH Protects Neurological Function Against Ischemic Stroke.

In recent years, orexin (ORX) and melanin-concentrating hormone (MCH) have been demonstrated to exert neuroprotective roles in cerebral ischemia. Hence, this study investigated the regulatory function of ORX and MCH in neurological function following ischemic stroke and explored the molecular mechanism underlying these functions. A rat model of ischemic stroke was developed by middle cerebral artery occlusion (MCAO), and Longa scoring was employed to evaluate the degree of neurological function deficit. The expression patterns of ORX and MCH were examined by real-time polymerase chain reaction in the brain tissues of rats with ischemic stroke induced by middle cerebral artery occlusion (MCAO). Moreover, electroencephalography (EEG) analysis and high-performance liquid chromatography (HPLC) were respectively performed to detect rapid-eye movement (REM) sleep, the glutamate (Glu) uptake, and the expression of γ-aminobutyric acid B receptor (GABAB). Immunoblotting was performed to test the levels of autophagic markers LC3, BECLIN-1, and p62. Immunohistochemistry (IHC) staining and TUNEL assays were respectively used to assess the autophagy and neuronal apoptosis. Results demonstrated that ORX and MCH were lowly expressed in brain of rats with ischemic stroke. ORX or MCH overexpression decreased neuronal apoptosis and autophagy, and improved the sleep architecture of post-stroke rats, while rescuing Glu uptake and GABA expression. ORX or MCH upregulation exerted protective effects on neurological function. Taken together, ORX and/or MCH protect against ischemic stroke in a rat model, highlighting their value as targets for the clinical treatment of ischemic stroke.

Practice, Knowledge, and Attitude of Health Care Providers regarding Cancer Pain Management: A National Survey.

Background: A lack of knowledge and inadequate practices of health care providers (HCPs) are the main obstacles to effective cancer pain management (CPM). The main objective of the study was to evaluate the CPM knowledge, CPM practice, and attitudes towards pharmacists' participation and advanced methods in CPM of physicians, nurses, and pharmacists in China. Methods: An open online survey was adopted using social media software (WeChat) as the platform to conduct a nationwide survey of HCPs involved in CPM in public medical institutions at all levels in China from March to June 2019. Results: A total of 1279 physicians, 2267 nurses, and 1466 pharmacists participated in the survey. Among the three types of professionals, nurses had the highest level of practical ability (61.63 ± 28.99) and best attitudes towards pharmacists' participation and advanced methods in CPM (72.05 ± 33.71) and physicians had the best mastery of CPM-related knowledge (69.60 ± 28.45), while pharmacists performed the worst in these three aspects (50.04 ± 26.69, 61.49 ± 28.95, and 62.07 ± 36.46, respectively). Only 19.69% of the hospitals had a pharmacist to tumor patient ratio ≥1 : 50. Hierarchical analysis showed that passing a good pain management (GPM) ward program and participating in advanced training had positive impacts on the scores of all three parts in the three professions (ptrend <0.05). Conclusions: HCPs' levels of practice, knowledge, and attitudes towards pharmacists and advanced methods of CPM were average in China; however, pharmacists had the worst performance, which demonstrates a need for further improvement. Furthermore, GPM ward programs and advanced trainings are helpful for improving CPM levels.

Robust Korean License Plate Recognition Based on Deep Neural Networks.

With the rapid rise of private vehicles around the world, License Plate Recognition (LPR) plays a vital role in supporting the government to manage vehicles effectively. However, an introduction of new types of license plate (LP) or slight changes in the LP format can break previous LPR systems, as they fail to recognize the LP. Moreover, the LPR system is extremely sensitive to the conditions of the surrounding environment. Thus, this paper introduces a novel deep learning-based Korean LPR system that can effectively deal with existing challenges. The main contributions of this study include (1) a robust LPR system with the integration of three pre-processing techniques (defogging, low-light enhancement, and super-resolution) that can effectively recognize the LP under various conditions, (2) the establishment of two original Korean LPR approaches for different scenarios, including whole license plate recognition (W-LPR) and single-character license plate recognition (SC-LPR), and (3) the introduction of two Korean LPR datasets (synthetic data and real data) involving a new type of LP introduced by the Korean government. Through several experiments, the proposed LPR framework achieved the highest recognition accuracy of 98.94%.

Does PSA level affect the choice of prostate puncture methods among MRI-ultrasound fusion targeted biopsy, transrectal ultrasound systematic biopsy or the combination of both?

OBJECTIVES: To explore whether prostate-specific antigen (PSA) affects the choice of prostate puncture methods by comparing MRI-ultrasound fusion targeted biopsy (MRI-TBx) with transrectal ultrasound systematic biopsy (TRUS-SBx) in the detection of prostate cancer (PCa), clinically significant prostate cancer (csPCa) and non-clinically significant prostate cancer (nsPCa) in different PSA groups (<10.0,10.0-20.0 and>20.0 ng ml-1). METHODS: A total of 190 patients with 215 lesions who underwent both MRI-TBx and TRUS-SBx were included in this retrospective study. PSA was measured pre-operatively and stratified to three levels. The detection rates of PCa, csPCa and nsPCa through different methods (MRI-TBx, TRUS-SBx, or MRI-TBx +TRUS SBx) were compared with stratification by PSA. RESULTS: Among the 190 patients, the histopathological results revealed PCa in 126 cases, including 119 csPCa. In PSA <10.0 ng ml-1 group, although the detection rates of PCa and csPCa by MRI-TBx were higher than those of TRUS-SBx, no significant differences were observed (p = 0.741; p = 0.400). In PSA 10.0-20.0 ng ml-1 group, difference between the detection rate of csPCa with TRUS-SBx and the combined method was statistically significant (p = 0.044). As for PSA >20.0 ng ml-1, MRI-TBx had a higher csPCa rate than TRUS-SBx with no statistical significance noted (p = 0.600). CONCLUSION: MRI-TBx combined with TRUS-SBx could be suitable as a standard detection approach for csPCa in patients with PSA 10.0-20.0 ng ml-1. As for PSA >20.0 and <10.0 ng ml-1, both MRI-TBx and TRUS-SBx might provide effective solutions for tumor detection. ADVANCES IN KNOWLEDGE: This study gives an account of choosing appropriate prostate puncture methods through PSA level.

Investigate on the Mechanism of HfO2/Si0.7Ge0.3 Interface Passivation Based on Low-Temperature Ozone Oxidation and Si-Cap Methods.

The interface passivation of the HfO2/Si0.7Ge0.3 stack is systematically investigated based on low-temperature ozone oxidation and Si-cap methods. Compared with the Al2O3/Si0.7Ge0.3 stack, the dispersive feature and interface state density (Dit) of the HfO2/Si0.7Ge0.3 stack MOS (Metal-Oxide-Semiconductor) capacitor under ozone direct oxidation (pre-O sample) increases obviously. This is because the tiny amounts of GeOx in the formed interlayer (IL) oxide layer are more likely to diffuse into HfO2 and cause the HfO2/Si0.7Ge0.3 interface to deteriorate. Moreover, a post-HfO2-deposition (post-O) ozone indirect oxidation is proposed for the HfO2/Si0.7Ge0.3 stack; it is found that compared with pre-O sample, the Dit of the post-O sample decreases by about 50% due to less GeOx available in the IL layer. This is because the amount of oxygen atoms reaching the interface of HfO2/Si0.7Ge0.3 decreases and the thickness of IL in the post-O sample also decreases. To further reduce the Dit of the HfO2/Si0.7Ge0.3 interface, a Si-cap passivation with the optimal thickness of 1 nm is developed and an excellent HfO2/Si0.7Ge0.3 interface with Dit of 1.53 × 1011 eV-1cm-2 @ E-Ev = 0.36 eV is attained. After detailed analysis of the chemical structure of the HfO2/IL/Si-cap/Si0.7Ge0.3 using X-ray photoelectron spectroscopy (XPS), it is confirmed that the excellent HfO2/Si0.7Ge0.3 interface is realized by preventing the formation of Hf-silicate/Hf-germanate and Si oxide originating from the reaction between HfO2 and Si0.7Ge0.3 substrate.

Comprehensive Landscape of Heparin Therapy for COVID-19.

The pandemic coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading globally. Clinical observations found that systemic symptoms caused by SARS-CoV-2 infection are attenuated when using the anticoagulant agent heparin, indicating that heparin may play other roles in managing COVID-19, in addition to prevention of pulmonary thrombosis. Several biochemical studies show strong binding of heparin and heparin-like molecules to the Spike protein, which resulted in inhibition of viral infection to cells. The clinical observations and in vitro studies argue for a potential multiple-targeting effects of heparin. However, adverse effects of heparin administration and some of the challenges using heparin therapy for SARS-CoV-2 infection need to be considered. This review discusses the pharmacological mechanisms of heparin regarding its anticoagulant, anti-inflammatory and direct antiviral activities, providing current evidence concerning the effectiveness and safety of heparin therapy for this major public health emergency.

A Comparative Analysis of Two Machine Learning-Based Diagnostic Patterns with Thyroid Imaging Reporting and Data System for Thyroid Nodules: Diagnostic Performance and Unnecessary Biopsy Rate.

Background: The risk stratification system of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for thyroid nodules is affected by low diagnostic specificity. Machine learning (ML) methods can optimize the diagnostic performance in medical image analysis. However, it is unknown which ML-based diagnostic pattern is more effective in improving diagnostic performance for thyroid nodules and reducing nodule biopsies. Therefore, we compared ML-assisted visual approaches and radiomics approaches with ACR TI-RADS in diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rate for thyroid nodules. Methods: This retrospective study evaluated a data set of ultrasound (US) and shear wave elastography (SWE) images in patients with biopsy-proven thyroid nodules (≥1 cm) from the Shanghai Tenth People's Hospital (743 nodules in 720 patients from September 2017 to January 2019) and an independent test data set from the Ma'anshan People's Hospital (106 nodules in 102 patients from February 2019 to April 2019). Six US features and five SWE parameters from the radiologists' interpretation were used for building the ML-assisted visual approaches. The radiomics features extracted from the US and SWE images were used with ML methods for developing the radiomics approaches. The diagnostic performance for differentiating thyroid nodules and the unnecessary FNAB rate of the ML-assisted visual approaches and the radiomics approaches were compared with ACR TI-RADS. Results: The ML-assisted US visual approach had the best diagnostic performance than the US radiomics approach and ACR TI-RADS (area under the curve [AUC]: 0.900 vs. 0.789 vs. 0.689 for the validation data set, 0.917 vs. 0.770 vs. 0.681 for the test data set). After adding SWE, the ML-assisted visual approach had a better diagnostic performance than US alone (AUC: 0.951 vs. 0.900 for the validation data set, 0.953 vs. 0.917 for the test data set). When applying the ML-assisted US+SWE visual approach, the unnecessary FNAB rate decreased from 30.0% to 4.5% in the validation data set and from 37.7% to 4.7% in the test data set in comparison to ACR TI-RADS. Conclusions: The ML-assisted dual modalities visual approach can assist radiologists to diagnose thyroid nodules more effectively and considerably reduce the unnecessary FNAB rate in the clinical management of thyroid nodules.

The Potential of Low Molecular Weight Heparin to Mitigate Cytokine Storm in Severe COVID-19 Patients: A Retrospective Cohort Study.

On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID-19) as a global pandemic. However, specific anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID-19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D-dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL-6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti-inflammatory effect and attenuate in part the "cytokine storm" induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical study.

Angelica sinensis polysaccharide attenuates CCl4-induced liver fibrosis via the IL-22/STAT3 pathway.

Angelica sinensis polysaccharide (ASP) has hepatoprotective effects in liver injury models. However, its role and mechanism in chronic liver fibrosis have not been fully elucidated. In this study, a carbon tetrachloride (CCl4)-induced chronic liver fibrosis mouse model was established. The results showed that ASP treatment reduced serum alanine aminotransferase by approximately 50% and liver fibrosis areas by approximately 70%. Hepatic stellate cell (HSC) activation was inhibited in ASP-treated mice. Furthermore, the mechanism was studied in-depth, focusing on the interleukin 22/signal transducer and activator of transcription 3 (IL-22/STAT3) axis. Concentrations of 50 µg/ml and 100 µg/ml ASP induced the secretion of IL-22 in vitro, which further increased at a concentration of 200 µg/ml. Moreover, in vivo data showed that ASP significantly promoted IL-22 production in splenocytes and liver tissues. The antifibrotic effects of ASP were abolished after IL-22 neutralization. In addition, ASP activated the STAT3 pathway in the liver, as demonstrated by a 2-fold increase compared to that of the CCl4 group, which was abrogated by the IL-22 antibody. Subsequently, we showed that the antifibrotic effects of ASP were abrogated by blocking STAT3 with S3I-201. In conclusion, ASP effectively alleviates chronic liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway.

Diagnostic Performance Evaluation of Practice Guidelines, Elastography and Their Combined Results for Thyroid Nodules: A Multicenter Study.

The purpose of this multicenter study was to compare the differential diagnostic value of the 2015 American Thyroid Association (ATA) and 2017 American College of Radiology (ACR) practice guidelines and elastography in thyroid nodules. This study also investigated whether the diagnostic value of practice guidelines can be improved, and the unnecessary biopsy rate decreased in combination with elastography. A total of 498 thyroid nodules were evaluated using the ATA and the ACR guidelines. Strain elastography, acoustic radiation force impulse imaging and point-shear wave elastography were used to assess the nodules. The suspicious levels were downgraded or upgraded after combination and unnecessary biopsy rates were calculated, respectively. The diagnostic performance of the practice guidelines was better than that of elastography. The ACR guidelines had a lower unnecessary biopsy rate and similar diagnostic performance compared with the ATA guidelines. The unnecessary biopsy rates significantly decreased when the ACR guidelines were combined with elastography, but the rates did not decrease when the ATA guidelines were combined with elastography.

Conventional ultrasound characteristics, TI-RADS category and shear wave speed measurement between follicular adenoma and follicular thyroid carcinoma.

The purpose of the study was to explore the differences of conventional ultrasound characteristics, thyroid imaging reporting and data system (TI-RADS) category and shear wave speed (SWS) measurement between follicular adenoma (FA) and follicular thyroid carcinoma (FTC). Twenty-eight FTCs and 67 FAs proven by surgery were retrospectively included for analysis. Conventional ultrasound and point-shear wave elastography (p-SWE) were performed in all of the included patients. The ultrasound features, American Thyroid Association (ATA) TI-RADS category and American College of Radiology (ACR) TI-RADS category, SWS measurement were compared between the two groups. Receiver operating characteristic (ROC) curve was performed and area under ROC curve (AUC) was obtained for significant features. There were no statistical differences in mean age (46.9±15.7years vs. 48.6±13.6years, P = 0.639), gender (9 males, 32.1% vs. 18 males, 29.0%, P = 0.766) and mean diameter (28.3±16.2 mm vs. 33.8±11.9 mm, P = 0.077) between FTCs and FAs. Hypoechogenicity, lobulated or irregular margin, macrocalcification were more common in FTCs than FAs (all P < 0.05). Mean SWS of FTCs (2.29±0.64 m/s) was slightly higher than that of FAs (1.94±0.68 m/s) (P = 0.023). The AUCs were 0.655, 0.744, and 0.744 with the cut-off SWS≥1.89 m/s, ACR TI-RADS category 4 and intermediate suspicion of ATA TI-RADS category. The sensitivity and AUC were 82.1% and 0.812 with combined ultrasound features of hypoechogenicity, lobulated or irregular margin and macrocalcification. In Conclusion, SWS measurement and TI-RADS categories were useful for the identification of FTCs from FAs.