OBJECTIVES: Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of WNT10A gene knockdown in PTC cell proliferation, invasion, and metastasis. METHODS: The expression of WNT10A in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure WNT10A mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by WNT10A were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway. RESULTS: WNT10A mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both P<0.01). The real-time RT-PCR result showed that WNT10A mRNA expression in PTC tissues was high than that in adjacent tissues (P<0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (P<0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. WNT10A knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all P<0.01). WNT10A silencing also reduced migration and invasion abilities in both cell lines. In vivo, WNT10A knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that WNT10A knockdown downregulated the expression of key genes (STAT3, MAPK8, TNFRSF21, and AKT2) in this pathway. CONCLUSIONS WNT10A is highly expressed in PTC and is associated with tumor proliferation, invasion, and metastasis. Its tumor-promoting effects may be mediated through suppression of the Tec kinase signaling pathway.
Humans ; Cell Proliferation ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/metabolism* ; Animals ; Wnt Proteins/metabolism* ; Neoplasm Invasiveness ; Mice ; Cell Line, Tumor ; Female ; Male ; Mice, Nude ; Apoptosis ; Lymphatic Metastasis ; Middle Aged ; Cell Movement ; Adult

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Dendritic cells (DC) represent a heterogeneous cell population including many subsets. DC subpopulations with different characteristics and functions have been identified. The liver, as an immunological organ, is important in induction of immune tolerance. The unique anatomical architecture and immune properties of the liver have given DC the ability to maintain liver homeostasis and respond quickly to liver tissue damage. This article reviewed the role of hepatic DC subsets in the maintenance of tissue homeostasis and repair of damaged tissue in the liver.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

In order to evaluate the safety performance of self-expandable NiTi alloy stents systematically, the dynamic safety factor drawn up by International Organization for Standardization, was used to quantitatively reflect the safety performance of stents. Based on the constitutive model of super-elastic memory alloy material in Abaqus and uniaxial tensile test data of NiTi alloy tube, finite element method and experiments on accelerated fatigue life were carried out to simulate the self-expansion process and the shape change process under the action of high and low blood pressure for three -type stents of 8×30 mm, 10×30 mm, 12×30 mm. By analyzing the changes of stress and strain of self-expanding NiTi alloy stent, the maximum stress and strain, stress concentration position, fatigue strength and possible failure modes were studied, thus the dynamic safety factor of stent was calculated. The results showed that the maximum stress and plastic strain of the stent increased with the increase of grip pressure, but the maximum stress and strain distribution area of the stent had no significant change, which were all concentrated in the inner arc between the support and the connector. The dynamic safety factors of the three stents were 1.31, 1.23 and 1.14, respectively, which indicates that the three stents have better safety and reliability, and can meet the fatigue life requirements of more than 10 years, and safety performance of the three stents decreases with the increase of stent's original diameter.
Alloys ; Finite Element Analysis ; Nickel ; Reproducibility of Results ; Self Expandable Metallic Stents ; Stress, Mechanical ; Titanium

Objective:To investigate the incidence rate, influencing factors and prognosis of infection-induced acute renal injury (AKI) in patients with acute-on-chronic liver failure (ACLF).Methods:516 cases with acute-on-chronic liver failure complicated with infection that were hospitalized in our hospital during 2014 to 2016 were retrospectively studied. General conditions and clinical characteristics of the patients were collected, and grouped according to the presence or absence of incidence and severity of AKI. General conditions, laboratory results, occurrence of complications and survival were compared and analyzed.Results:The main causes were HBV infection (67.8%) and alcoholic liver disease (20.0%). The most common sites of infection were abdominal cavity, lung and blood. Multivariate analysis showed that neutrophil count, TBIL, lactate and septic shock were independent risk factors for infection-induced AKI in ACLF patients. The cumulative mortality in patients with AKI after infection at 28, 90 and 360 days was significantly higher than those without AKI (51.6% and 20.5%, 70.2% and 40.3%, 73.4% and 45.9%; P < 0.01). In both groups, deaths had occurred mainly in the early (0 ~ 28 d) and middle (29 ~ 90 d) stage of follow-up period. In the late follow-up period (91-360 d), there was no statistically significant difference in mortality rate between the two groups. Conclusion:Infection is an important inducing cause of AKI in ACLF patients. The underlying liver disease and the severity of infection are significantly related to the infection-induced AKI in ACLF patients, and once AKI occurs after infection, the mortality rate of the patients is significantly increased.

To compare the clinical value of superb microvascular imaging (SMI) and contrast enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules, and to further study whether the combination of SMI and/or CEUS with thyroid imaging reporting and data system (TI-RADS) can improve the diagnostic value of TI-RADS.
 Methods: SMI, CEUS, TI-RADS, TI-RADS combined with CEUS, TI-RADS combined with SMI, TI-RADS combined with SMI and CEUS were used to differentiate thyroid nodules. TI-RADS 4b, 5 categories in two-dimensional ultrasound, hypoenhancement in CEUS, and peripheral blood flow with penetrating vessels in SMI were considered malignant signs. The diagnostic efficacy of these methods was compared according to post-operative pathology or fine needle aspiration cytology.
 Results: A total of 237 patients with 296 thyroid nodules were included in the study. The sensitivity, specificity and accuracy for TI-RADS were 78.4%, 77.7% and 78.0% respectively, 75.5%, 86.6% and 81.4% in SMI, 82.0%, 88.5% and 85.5% in CEUS, 92.1%, 90.4% and 91.2% in TI-RADS combined with SMI and CEUS. Area under the receiver operating characteristic curve (AUROC) showed no significant difference between SMI, CEUS, TI-RADS (χ2=4.29, P=0.117). AUROC of both TI-RADS combined with CEUS (χ2=39.62, P<0.001), TI-RADS combined with SMI (χ2=36.61, P<0.001) were higher than TI-RADS. AUROC of TI-RADS combined with SMI and CEUS was higher than TI-RADS combined with SMI (χ2=4.50, P=0.033) or TI-RADS combined with CEUS (χ2=4.24, P=0.039).
 Conclusion: Peripheral blood flow with penetrating vessels in SMI possesses high diagnostic value in differentiating thyroid cancer. The combination of SMI and/or CEUS with TI-RADS can be used to improve the diagnostic efficacy of TI-RADS in differential diagnosis of thyroid nodules.
Diagnosis, Differential ; Humans ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography

Objective To verify and compare the TI-RADS developed by Kwak et al .( Kwak TI-RADS ) ,2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer ( ATA Guideline Classification) ,2017 TI-RADS released by the American College of Radiology (ACR TI-RADS) and TI-RADS developed by Zhou et al .(Zhou TI-RADS) in the evaluation of thyroid nodules . Methods The ultrasound images of 339 thyroid nodules in 273 patients were analyzed by retrospective study . The thyroid nodules were categorized into aforementioned four stratified systems . Based on the pathological findings considered the "gold standard",the receiver operating characteristic( ROC ) curve was created to compare the clinical application value of aforementioned four stratified systems . Results The percentage of nodules that could not be categorized were 1 .2％ ,17 .5％ ,0 and 1 .2％ for the Kwak TI-RADS ,ATA guidelines ,ACR TI-RADS ,and Zhou TI-RADS ,respectively and the area under the ROC curve ( AUC) was 0 .899 ,0 .879 ,0 .876 ,and 0 .918 ,respectively . The sensitivity of Kwak TI-RADS ,ATA guidelines classification ,and ACR TI-RADS were higher than that of Zhou TI-RADS (all P < 0 .05) ,whereas the specificity of Zhou TI-RADS was the highest (all P < 0 .05) . As for the accuracy ,no statistically significant differences were observed between any two of Kwak TI-RADS ,ATA guidelines ,ACR TI-RADS ,and Zhou TI-RADS systems ( all P > 0 .05) . Conclusions Four thyroid risk stratification systems provide effective risk assessment for thyroid nodules ,Zhou TI-RADS has relatively lower sensitivity ,but its specificity and AUC value are the highest among the four evaluated systems . In addition ,ACR TI-RADS can classify the most nodules ,while the number of nodules that can′t be categorized by ATA guideline is maximum .

Objective To analyze the relationship between fatigue strength and connector length of intracranial artery stents, so as to investigate the exact location of fatigue fracture for the stent. Methods The fatigue life for 3 kinds of artery stents were analyzed by finite element analysis method of fatigue fracture, and distribution map of dangerous points was drawn by means of Goodman curve. Based on F2477-07 standard from American Society for Testing and Materials (ASTM), the fatigue life for 3 kinds of stents was tested. Results If the length of the support connector was longer, the maximum equivalent stress and the average stress in dangerous points of the stent would be larger. If the distribution of dangerous points was more close to the curve of fatigue limit, and fatigue fracture was more likely to occur in the stent. Goodman curves indicated that 3 kinds of stents was safe to be used in the body for ten years. Finite element analysis and experimental result showed that fatigue life near the stent junction was relatively lower, and dangerous points of the stent was located at the arc junction. Conclusions It is reasonable to study stents by finite element analysis, whose results are basically coincided with the experimental data. Fatigue life can be extended by reducing connector’s length for the design of stent structure.