Predicting papillary thyroid microcarcinoma in American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules: radiomics analysis based on intratumoral and peritumoral ultrasound images.

Background: A subset of patients undergoing thyroid surgery for presumed benign thyroid disease presented with papillary thyroid microcarcinoma (PTMC). A non-invasive and precise method for early recognition of PTMC are urgently needed. The aim of this study was to construct and validate a nomogram that combines intratumoral and peritumoral radiomics features as well as clinical features for predicting PTMC in the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules using ultrasonography. Methods: A retrospective review was conducted on a cohort of 221 patients who presented with ACR TI-RADS 3 nodules. These patients were subsequently pathologically diagnosed with either PTMC or benign thyroid nodules. These patients were randomly divided into a training and test cohort with an 8:2 ratio for developing the clinical model, intratumor-region model, peritumor-region model and the combined-region model respectively. The radiomics features were extracted from ultrasound (US) images of each patient. We employed K-nearest neighbor (KNN) model as the base model for building the radiomics signature and clinical signature. Finally, a radiomics-clinical nomogram that combined intratumoral and peritumoral radiomics features as well as clinical features was developed. The prediction performance of each model was assessed by the area under the curve (AUC), sensitivity, specificity and calibration curve. Results: A total of 23 radiomics features were selected to develop radiomics models. The combined-region radiomics model showed favorable prediction efficiency in both the training dataset (AUC: 0.955) and the test dataset (AUC: 0.923). A radiomics-clinical nomogram was constructed and achieved excellent calibration and discrimination, which yielded an AUC value of 0.950, a sensitivity of 0.950 and a specificity of 0.920. Conclusions: This study proposed the nomogram that contributes to the accurate and intuitive identification of PTMC in ACR TI-RADS 3 nodules.

The preferred surgical choice for intermediate-risk papillary thyroid cancer: total thyroidectomy or lobectomy? A systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for intermediate-risk papillary thyroid carcinoma (IR-PTC) (according to ATA definition), whether total thyroidectomy (TT) or lobectomy (LT), has remained a contentious clinical gray area for several decades. This systematic review and meta-analysis aim to provide robust evidence and address this clinical dilemma comprehensively. MATERIALS AND METHODS: A comprehensive literature search was conducted in Pubmed, Embase, Web of Science, and the Cochrane Library from 1st January 2009 to 29th December 2023 to evaluate the impact of different surgical options (TT or LT) on patients with IR-PTC. The primary outcomes included survival, recurrence rates, and postoperative complications. I2 and sensitivity analysis was used to explore the heterogeneity. RESULTS: A total of 8 studies involving 2984 participants were included in this meta-analysis and systematic review. The results indicated that LT was a superior choice for mitigating complications compared to TT [risk ratio (RR), 0.32; 95% CI: 0.24-0.44, P <0.01], particularly for transient complications (RR, 0.24; 95% CI: 0.08-0.65, P <0.01), such as the transient parathyroid dysfunction (RR, 0.04; 95% CI: 0.01-0.15, P <0.01). However, TT did not increase the risk of recurrent laryngeal nerve palsy (RR, 0.78; 95% CI: 0.24-2.47, P =0.67), hemorrhage/seroma (RR, 0.77; 95% CI: 0.48-1.25, P =0.30), and permanent complications (RR, 0.18; 95% CI: 0.02-1.42, P =0.10). Besides, both LT and TT presented similar effect on survival outcomes (overall survival: RR, 1.00; 95% CI: 0.97-1.03, P =0.92, disease-specific survival: RR, 0.99; 95% CI: 0.97-1.02, P =0.69, recurrence-free survival: RR, 1.00; 95% CI: 0.96-1.05, P =0.86), recurrence (RR, 1.05; 95% CI: 0.76-1.46, P =0.76). CONCLUSION: The present meta-analysis revealed that TT did not yield improved outcomes in IR-PTC patients, but was associated with an increased incidence of temporary complications. In light of these findings, it may be advisable to consider LT as the optimal choice for IR-PTC patients.

Intestinal lymphatic transport of Smilax china L. pectic polysaccharide via Peyer's patches and its uptake and transport mechanisms in mononuclear phagocytes.

Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.

The ultrasound-based radiomics-clinical machine learning model to predict papillary thyroid microcarcinoma in TI-RADS 3 nodules.

Background: Conventional ultrasound (CUS) technology has proven to be successful in the identification of thyroid nodules. Moreover, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) was developed for the purpose of evaluating the risk of thyroid nodules based on ultrasound imaging. Nevertheless, identifying papillary thyroid microcarcinoma (PTMC) from TI-RADS 3 nodules using this system can be difficult due to overlapping morphological features. The main objective of this study was to investigate the efficacy of a machine learning model that utilizes ultrasound-based radiomics features and clinical information in accurately predicting the presence of PTMC in TI-RADS 3 nodules. Methods: A total of 221 patients with TI-RADS 3 nodules were included, consisting of 91 cases of PTMC and 130 benign thyroid nodules. They were randomly divided into training and test cohort in an 8:2 ratio. Radiomics features were extracted from CUS images by manually outlining the targets, while clinical parameters were obtained from electronic medical records. The radiomics model, clinical model, and combined model were constructed and validated to distinguish between PTMC and benign thyroid nodules. Radiomics variables were extracted via the Pyradiomics package (V1.3.0). Moreover, least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Light Gradient Boosting Machine (LightGBM) was employed to build both radiomics and clinical models. Ultimately, a radiomics-clinical model, which fused radiomics features with clinical information, was developed. Results: Among a total of 1,477 radiomics features, fifteen features that were found to be associated with PTMC through univariate analysis and LASSO regression were selected for the development of the radiomics model. The combined "radiomics-clinical" model demonstrated superior diagnostic accuracy compared to the clinical model for distinguishing PTMC in both the training dataset [area under receiver operating curve (AUC): 0.975 vs. 0.845] and the validation dataset (AUC: 0.898 vs. 0.811). We constructed a radiomics-clinical nomogram, and the clinical applicability was confirmed through decision curve analysis. Conclusions: Utilizing an ultrasound-based radiomics approach has proven to be effective in predicting PTMC in patients with TI-RADS 3 nodules.

Structural characterisation and structure-antioxidant activity relationship of polysaccharides from Dendrobium catenatum Lindl.

Dendrobium catenatum Lindl. has been long used in China as a functional food and traditional Chinese medicine and polysaccharides from Dendrobium catenatum Lindl. (DOP) exhibited extensive bioactivities. However, studies on the structure-activity relationship of DOP are rarely reported. Here, two polysaccharides named DOP-1 and DOP-2 were obtained, which differed in the ratio of monosaccharide composition and molecular weight. Structural characteristics were elucidated by spectral and chemical analysis. The main structures of DOPs were the linkage of ß-(1→4)-D-Manp, with some attached 2-O- or 3-O-acetylated groups. Additionally, the DPPH, hydroxyl and superoxide radicals scavenging assays of DOP-1 and DOP-2 showed that DOP-2 exhibited the higher antioxidant activity, which might be related to its lower molecular weight, higher mannose proportion and lower degree of acetylation, and higher phenolic content. Our results provide a more accurate basis for the application of DOPs in the pharmaceutical and food industries.

Interfacial Engineering of Polycrystalline Pt5 P2 Nanocrystals and Amorphous Nickel Phosphate Nanorods for Electrocatalytic Alkaline Hydrogen Evolution.

Electrocatalytic hydrogen evolution reaction (HER) in alkaline media is important for hydrogen economy but suffers from sluggish reaction kinetics due to a large water dissociation energy barrier. Herein, Pt5 P2 nanocrystals anchoring on amorphous nickel phosphate nanorods as a high-performance interfacial electrocatalyst system (Pt5 P2 NCs/a-NiPi) for the alkaline HER are demonstrated. At the unique polycrystalline/amorphous interface with abundant defects, strong electronic interaction, and optimized intermediate adsorption strength, water dissociation is accelerated over abundant oxophilic Ni sites of amorphous NiPi, while hydride coupling is promoted on the adjacent electron-rich Pt sites of Pt5 P2 . Meanwhile, the ultra-small-sized Pt5 P2 nanocrystals and amorphous NiPi nanorods maximize the density of interfacial active sites for the Volmer-Tafel reaction. Pt5 P2 NCs/a-NiPi exhibits small overpotentials of merely 9 and 41 mV at -10 and -100 mA cm-2 in 1 M KOH, respectively. Notably, Pt5 P2 NCs/a-NiPi exhibits an unprecedentedly high mass activity (MA) of 14.9 mA µgPt -1 at an overpotential of 70 mV, which is 80 times higher than that of Pt/C and represents the highest MA of reported Pt-based electrocatalysts for the alkaline HER. This work demonstrates a phosphorization and interfacing strategy for promoting Pt utilization and in-depth mechanistic insights for the alkaline HER.

Glioma targeted therapy: insight into future of molecular approaches.

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

Experimental study on renoprotective effect of intermedin on diabetic nephropathy.

Intermedin(IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family that has anti-inflammatory, antioxidant and anti-apoptosis properties. This study aimed to evaluate the renoprotective effects of IMD on podocyte apoptotic loss and slit diaphragm protein deficiency the kidneys of rats with in streptozotocin (STZ) induced diabetes in high glucose-exposed podocytes. Our results showed that IMD significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure in vivo. IMD also improved the induction of slit diaphragm proteins, and restored the decreased Bcl-2 expression and suppressed Bax and caspase-3 induction in the diabetic glomeruli. In addition, IMD attenuated podocyte apoptosis and filamentous actin (F-actin) rearrangement in high glucose-exposed podocytes. Exposure to high glucose elevated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress in renal podocytes, and IMD treatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vivo and in vitro. These observations demonstrate that targeting ER stress is an underlying mechanism of IMD-mediated amelioration of diabetes-associated podocyte injury and dysfunction.

Intermedin Alleviates Renal Ischemia-Reperfusion Injury and Enhances Neovascularization in Wistar Rats.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and increases the risk of subsequently developing chronic kidney disease. Angiogenesis has been shown to play an important role in reducing renal injury after ischemia reperfusion. In this study, we investigated whether IMD could reduce renal IRI by promoting angiogenesis. METHODS: The kidneys of Wistar rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. IMD was overexpressed in vivo using the vector pcDNA3.1-IMD transfected by an ultrasound-mediated system. The renal injury after ischemia reperfusion was assessed by detection of the serum creatinine concentration and histologic examinations of renal tissues stained by PAS and H&E. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Histological examinations were used to assess the expression of CD31, MMP2, MMP9, ET-1, VEGF and VEGFR2 in tissues. RESULTS: Renal function and renal histological damage were significantly ameliorated in IMD-transfected rats after ischemia reperfusion. Compared to the IRI, IMD significantly promoted angiogenesis. IMD also upregulated the protein and mRNA expression levels of VEGF and VEGFR2 and downregulated the expression level of MMP2, MMP9 and ET-1. CONCLUSION: IMD could protect the kidney after renal ischemia-reperfusion injury by promoting angiogenesis and reducing the destruction of the perivascular matrix.

A novel function of CYP21A2 in regulating cell migration and invasion via Wnt signaling.

CYP21A2, which is responsible for 21-hydroxylase activity, is prominent to the development of congenital adrenal hyperplasia (CAH). The aim of our current study is to investigate the role of CYP21A2 in the tumor processes. Here, we used HepG2 cell lines and generated CYP21A2 overexpressing vector and siRNA to investigate the effect of CYP21A2 on the tumor development processes, particularly cell migration and invasion; genes expression related to these processes were further examined. Results showed that CYP21A2 over-expressed or silenced had no effects on cell viability as well as the process of cell apoptosis. Further study suggested that CYP21A2 silenced significantly decreased the G0/G1 phase and increased the S phase of the cell cycle. However, no differences were observed when CYP21A2 was overexpressed. Moreover, we found that cell migration and invasion significantly improved with CYP21A2 overexpressed and impaired with silenced CYP21A2. Finally, we examined the expression of genes related to tumor processes and found that the Wnt signaling genes were changed. Taken together, our results demonstrated a novel function of CYP21A2 in the regulation of tumor processes, particularly cell migration and invasion, which this may be mediated by the Wnt signaling pathway.

A comparative study on the structures of Grifola frondosa polysaccharides obtained by different decolourization methods and their in vitro antioxidant activities.

Decolourization of polysaccharides is one of the crucial procedures that affects their structure, which is closely related to their bioactivity. Here, Grifola frondosa polysaccharide (GFP) was decolourized with H2O2 and AB-8 macroporous resin. Then, two main fractions, named DGFP and SGFP, were obtained by purification with Sepharose CL-4B. The molecular weights of these two polysaccharides were determined to be 6.306 × 106 (±0.410%) Da and 1.174 × 107 (±0.299%) Da by HPSEC. Monosaccharide analysis indicated that DGFP was composed of glucose, mannose, and galactose (32.20 : 1.00 : 1.75), while SGFP consisted entirely of glucose. Despite a backbone →4)-α-Glcp-(1→ in two polysaccharides, reducing ends Rα →3)-α-Glcp and Rß â†’4)-ß-Glcp were observed in DGFP by 1D/2D NMR. The results suggested that decolourization with low concentrations of H2O2 might alter the structure of GFP and generate new reducing ends. In vitro antioxidant results implied that DGFP exhibited a higher ability to scavenge DPPH and hydroxyl radicals and reduced the over-generated ROS levels in a concentration-dependent manner. These results suggested that the antioxidant effects of GFP could be activated by decolourization with H2O2. Therefore, DGFP might be a more promising natural antioxidant than SGFP.

Intermedin protects HUVECs from ischemia reperfusion injury via Wnt/ß-catenin signaling pathway.

Intermedin (IMD) is a member of the calcitonin gene-related peptide (CGRP) superfamily and a pro-angiogenic factor. In the present study, we identified activation of the Wnt/ß-catenin signaling pathway by IMD. Adding CoCl2 HUVECs was used to establish an in vitro model. The migration of HUVECs was measured by wound healing assays and transwell migration assays. Capillary formation was measured using tube formation assays. Immunocytochemistry (ICC) analysis was used to evaluate VEGF and RAMP2 expression in HUVECs. The relevant signaling molecules were detected with western blot. Our study shows that IMD could promote H/R impaired HUVECs migration and tube formation in vitro. On the other hand, inhibition of Wnt/ß-catenin signaling led to the suppression of this promotion of migration and tube formation. This result suggests that Wnt/ß-catenin signaling is correlated to IMD induced angiogenesis. Analysis of results from ICC assays indicated that IMD works through increasing levels of VEGF and RAMP2. Meanwhile, the Wnt/ß-catenin signaling specific inhibitor IWR-1-endo was shown to down-regulate VEGF and RAMP2 expression. Western blot results further confirmed the signaling mechanism by which IMD promotes angiogenesis. Thus, Wnt/ß-catenin signaling plays an important role in IMD induced neovascularization. The data further suggest that the PI3K axis contributes positively downstream.