Overexpression of NR1D1 portends disease recurrence in thyroid cancer.

CONTEXT: Dysregulation of circadian rhythms has been linked to cancer susceptibility. Thyroid cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts. OBJECTIVE: Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid cancer and explore its prognostic and translational implications. METHODS: We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms. RESULTS: Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid cancer cells. The invasion-promoting effect of NR1D1 was regulated by the ß-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo. CONCLUSION: NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid cancer.

Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Responses of nitrobenzene removal performance and microbial community by modified biochar supported zerovalent iron in anaerobic soil.

Biochar-supported ZVI have received increasing attention for their potential to remove nitrobenzene in groundwater and soil. However, the capacity of this material to enhance the biological reduction of nitrobenzene and alter microbial communities in anaerobic groundwater have not been explored. In this study, the nitrobenzene removal performance and mechanism of modified biochar-supported zerovalent iron (ZVI) composites were explored in anaerobic soil. The results showed that the 700 °C biochar composite enhanced the removal of nitrobenzene and inhibited its release from soil to the aqueous phase. NaOH-700-Fe50 had the highest removal rate of nitrobenzene, reaching 64.4%. However, the 300 °C biochar composite inhibited the removal of nitrobenzene. Microbial degradation rather than ZVI-mediated reduction was the main nitrobenzene removal pathway. The biochar composites changed the richness and diversity of microbial communities. ZVI enhanced the symbiotic relationship between microbial genera and weakened competition between soil microbial genera. In summary, the 700 °C modified biochar composite enhanced the removal of nitrobenzene by increasing microbial community richness and diversity, by upregulating functional genes, and by promoting electron transfer. Overall, the modified biochar-supported ZVI composites could be used for soil remediation, and NaOH-700-Fe50 is a promising composite material for the on-site remediation of nitrobenzene-contaminated groundwater.

DUSP22-rearranged primary cutaneous CD30-positive T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma frequently share the LEF1+/TIA1- immunophenotype.

DUSP22 rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1- immunoprofile and MSC E116K mutations are highly associated with DUSP22 rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and MSC mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and MSC mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. DUSP22 rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) DUSP22-rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking DUSP22 rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all DUSP22-rearranged C-ALCL/LyP and ATLL cases tested. MCS E116K mutation was identified in one of five DUSP22-rearranged C-ALCL cases. RNA sequencing of a DUSP22-rearranged C-ALCL revealed a novel DUSP22::SNHG fusion coexisting with a CD58::WNT2B fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in DUSP22-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1- immunoprofile does not differentiate DUSP22-rearranged C-ALCL/LyP from ATLL.

Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

Study on the anti-cancer activity of α-phenethylamine ferrocenecarboxylic acid co-crystals.

Ferrocene derivatives show a wide range of pharmacological activities in the medical field, especially in the anti-tumor field, and can be used as candidate drugs or lead compounds for the treatment of tumors and other diseases. And α-phenethylamine is an important intermediate for the preparation of fine chemical products. (R)-(+)-1-Phenethylamine ferrocenecarboxylic acid/(S)-(-)-1-phenethylamine ferrocenecarboxylic acid were prepared, named compounds 1 and 2, respectively. Single crystal X-ray diffraction showed that compounds 1 and 2 crystallized in the orthorhombic system space group P21 21 21 , and the crystal structures of compounds 1 and 2 exhibited mirror symmetry. The inhibitory effect of two compounds on SW480, MDA-MB-231, and H1299 cells was tested by MTT colorimetry. The IC50 values of the compounds against cancer cells were also calculated. The anti-cancer effect was more pronounced for compounds in the S-configuration. Compound 2 made the wild-type cancer cells undergo apoptosis, thus preventing cancer; it also had the function of helping the cell gene repair defects.

Comprehensive evaluation of benign and malignant etiologies of different serous effusions with the International System for Reporting Serous Fluid Cytopathology: A multi-institutional study in Taiwan.

BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was introduced globally in 2019 in response to the absence of a standardized reporting system for serous fluid cytology. This study presents experiences implementing this system across three distinct hospitals in Taiwan. METHODS: A total of 6177 serous fluid specimens in three hospitals in Taiwan between 2018 and 2020 were retrospectively reviewed and reclassified according to the ISRSFC. Cytohistological correlation and chart review were further performed to investigate etiologies and risks of malignancy (ROMs). RESULTS: Reclassification showed that 34 (0.7%) of 4838 pleural effusions were nondiagnostic (ND), 4086 (84.5%) were negative for malignancy (NFM), 201 (4.2%) were atypia of undetermined significance (AUS), 92 (1.9%) were suspicious for malignancy (SFM), and 425 (8.8%) were malignant (MAL). The 1231 ascites cases contained 13 (1.1%) ND, 1004 (81.6%) NFM, 53 (4.3%) AUS, 31 (2.5%) SFM, and 130 (10.6%) MAL specimens. In pleural effusions, the ROM was 2.9% for ND, 14.0% for NFM, 52.2% for AUS, 85.9% for SFM, and 95.1% for MAL. In ascites, it was 15.4% for ND, 19.1% for NFM, 52.8% for AUS, 83.9% for SFM, and 92.3% for MAL. In pericardial effusions, it was 0.0% for ND, 11.6% for NFM, 30.8% for AUS, 100.0% for SFM, and 95.2% for MAL. Different effusions' most common benign and malignant etiologies were also disclosed. CONCLUSIONS: These multi-institutional data have determined the diagnostic usefulness of the ISRSFC, which provides pathologists and physicians with invaluable assistance in correctly classifying effusions for further management.

Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells.

Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia. SIGNIFICANCE: Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.

A study on the effectiveness of sodium selenite in treating cadmium and perfluoro octane sulfonic (PFOS) poisoned zebrafish (Danio rerio).

Perfluoro octane sulfonate (PFOS) and cadmium (Cd) are toxic elements in the environment. As a micronutrient trace element, selenium (Se) can mitigate the adverse effects induced by PFOS and Cd. However, few studies have examined the correlation between Se, PFOS and Cd in fish. The present study focused on the antagonistic effects of Se on PFOS+Cd-induced accumulation in the liver of zebrafish. The fish was exposed to PFOS (0.08mg/L), Cd (1mg/L), PFOS+ Cd (0.08 mg/L PFOS+1 mg/L Cd), L-Se (0.07mg/L Sodium selenite +0.08mg/L PFOS+1mg/L Cd), M-Se (0.35mg/L Sodium selenite + 0.08mg/L PFOS+ 1 mg/L Cd), H-Se (1.75 mg/L Sodium selenite + 0.08 mg/L PFOS+ 1mg/L Cd) for 14d. The addition of selenium to fish exposed to PFOS and Cd has been found to have significant positive effects. Specifically, selenium treatments can alleviate the adverse effects of PFOS and Cd on fish growth, with a 23.10% improvement observed with the addition of T6 compared to T4. In addition, selenium can alleviate the negative effects of PFOS and Cd on antioxidant enzymes in zebrafish liver, thus reducing the liver toxicity caused by PFOS and Cd. Overall, the supplementation of selenium can reduce the health risks to fish and mitigate the injuries caused by PFOS and Cd in zebrafish.

Cytological Features of a Metastatic Angiosarcoma in the Lymph Node Diagnosed via Liquid-Based Cytology.

Angiosarcoma is a soft tissue sarcoma of vascular origin, with more than half of the cases arising in the skin and affecting primarily the face and scalp of elderly males. Furthermore, cutaneous angiosarcoma exhibits a higher incidence of lymph node metastases than other types of sarcomas. Angiosarcomas are rarely aspirated and are occasionally encountered on cytological samples. It is a diagnostic challenge in evaluating fine needle aspiration (FNA) from a metastatic angiosarcoma without the knowledge of prior history. We present a case of scalp angiosarcoma with disease progression to erythroderma and cervical lymphadenopathy 20 months after. FNA of the cervical node revealed vasoformative features, including hemophagocytosis, formation of an intracytoplasmic lumen/vacuole, endothelial wrapping, and cell grasping. The diagnosis of nodal metastasis by angiosarcoma was confirmed with immunohistochemistry (IHC) using two vascular markers on cell block sections. Our case demonstrates the recognizable cytomorphologic clues for this rare metastatic malignancy.

Prevention for moderate or severe BPD with intravenous infusion of autologous cord blood mononuclear cells in very preterm infants-a prospective non-randomized placebo-controlled trial and two-year follow up outcomes.

Background: Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. Methods: This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18-24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Findings: Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3-20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p = 0.018). There was no statistical significant difference in total BPD incidence (adjusted p = 0.106) or mortality (p = 1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p = 0.047). Specific immune cells including proportion of T cells (p = 0.04) and CD4+ T cells in lymphocytes (p = 0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p ï¼œ 0.001). Anti-inflammatory factor IL-10 was higher (p = 0.03), while pro-inflammatory factor such as TNF-a (p = 0.03) and C reactive protein (p ï¼œ 0.001) level was lower in intervention group than in control group after intervention. Interpretation: ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. Funding: This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation.

OBJECTIVE: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. METHODS: Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. RESULTS: The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. CONCLUSION: Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.

Autologous cord blood mononuclear cell infusion for the prevention of bronchopulmonary dysplasia in very preterm monozygotic twins: A study protocol for a randomized, placebo-controlled, double-blinded multicenter trial.

Background: Preterm-associated complications remain the main cause of neonatal death. Survivors face the challenges of short- and long-term complications. Among all complications, bronchopulmonary dysplasia (BPD) remains the first important cause of neonatal mortality and morbidity. Current treatment does not address this main preterm complication. Cord blood is regarded as a convenient source of stem cells. The paracrine bioactive factors of stem cells contribute to tissue repair and immune modulation. Our clinical studies and those of others have shown that cord blood cell infusion is both safe and possibly effective in the prevention and treatment of BPD. The therapeutic use of cord blood has emerged as a promising therapy. However, the genetic heterogeneity between control and intervention groups may reduce the comparability especially among small sample trials. The purpose of this study protocol is to investigate the effects of autologous cord blood mononuclear cell (ACBMNC) infusion on the prevention of BPD in very preterm monozygotic twins of less than 32 gestation weeks. Methods: In this prospective, randomized, placebo-controlled, double-blinded multicenter clinical trial, 60 pairs of monozygotic twin preterm neonates of less than 32 weeks admitted to the Neonatal Intensive Care Unit are randomly assigned to receive intravenous ACBMNC infusion (targeted at 5 × 107 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age. The secondary outcomes will include the mortality rate, BPD severity, other common preterm complication rates, respiratory support duration, length and cost of hospitalization, and long-term respiratory and neurodevelopmental outcomes during a 2-year follow-up. Furthermore, we will perform single-cell RNA sequencing for cord blood cells and blood cells 3-10 days after intervention and detect whether reactive oxygen species and inflammatory cytokines are present. Conclusion: This will be the first randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of ACBMNC infusion to prevent BPD in monozygotic twin premature infants and investigate the underlying protective mechanisms. The results of this trial will provide valuable clinical evidence for translational application of cord blood cell therapy in very preterm infants.Trial registration: ClinicalTrials.gov, NCT05087498, registered 10/09/2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BAD7&selectaction=Edit&uid=U0002PLA&ts=2&cx=qvyylv.

Hidden blood loss of minimally invasive hybrid lumbar interbody fusion: an analysis of influencing factors.

BACKGROUND: Lumbar interbody fusion(LIF) is the leading way to treat Lumbar Degenerative Diseases(LDD). At present, there is a lack of research on the influencing factors of hidden blood loss in minimally invasive hybrid lumbar interbody fusion. This study comprehensively explores the definite factors affecting the hidden blood loss in minimally invasive hybrid lumbar interbody fusion. MATERIALS AND METHODS: One hundred patients with Lumbar degenerative diseases who underwent minimally invasive hybrid lumbar interbody fusion in our center were included. Demographics, laboratory data, surgical data, and radiographic data were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multi-factor linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: We reviewed and collected 100 patients who underwent minimally invasive hybrid approach, mean age 65 ± 10 years, male: female 37:63; 17 patients of diabetes and 83 patients of non-diabetes; Total blood loss was 645.59 ± 376.37 ml, hidden blood loss was 421.39 ± 337.45 ml, the hidden blood loss percentage was 57 ± 26%. Results from the multi-factorial linear regression model: Diabetes (p < 0.05), hypertension (p < 0.05), psoas thickness (p < 0.05) and dorsal extensor group thickness (p < 0.05) were potential risk factors for postoperative hidden blood loss. CONCLUSION: Although minimally invasive hybrid approach is minimally invasive surgery, there is still a significant amount of hidden blood loss. There is a greater risk of blood loss in diabetes, hypertension and preoperative MRI assessment of thickness of the psoas, thickness of the dorsal extensor group.

Aberrant Expression of Thymosin Beta-4 Correlates With Advanced Disease and BRAF V600E Mutation in Thyroid Cancer.

Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.

CRABP2 Is Associated With Thyroid Cancer Recurrence and Promotes Invasion via the Integrin/FAK/AKT Pathway.

Cellular retinoic acid-binding protein 2 (CRABP2) participates in retinoid partitioning between different nuclear receptors. Recently, we identified that CRABP2 is one of the progression-associated genes in thyroid cancer. To explore the prognostic and functional significance of CRABP2, immunohistochemical analysis was performed in thyroid tissues and neoplasms. Overexpression of CRABP2 was observed in malignant thyroid neoplasms but not in benign thyroid lesions. CRABP2 expression was an independent predictive factor for recurrence-free survival in patients with differentiated thyroid cancer. Knockdown of CRABP2 reduced the sensitivity of thyroid cancer cells to retinoic acid. Importantly, CRABP2 expression in thyroid cancer cells was associated with epithelial-mesenchymal transition properties, including anoikis resistance, migration, and invasion capacity. Furthermore, invasion promoted by CRABP2 was mediated at least partly by the integrin/focal adhesion kinase/AKT pathway. In summary, CRABP2 expression is upregulated in thyroid cancer with adverse prognostic implications. The invasion-stimulating effects appear independent of canonical retinoic acid signaling and may serve as a potential therapeutic target.

US Shear-Wave Elastography Dispersion for Characterization of Chronic Liver Disease.

Background Little is known about the benefits of the use of dispersion slope (DS) as a viscosity-related parameter derived from two-dimensional (2D) shear-wave elastography (SWE) in the stratification of hepatic pathologic stages. Purpose To evaluate whether DS as an additional parameter can improve the diagnostic performance in detecting liver necroinflammation, fibrosis, and steatosis. Materials and Methods In this prospective study, consecutive participants with chronic liver disease who underwent liver biopsy and 2D SWE were recruited between July 2019 and September 2020. DS and liver stiffness (LS) measurements were obtained with use of a 2D SWE system immediately before biopsy. The biopsy specimens were assessed to obtain the scores of fibrosis, necroinflammation, and steatosis. Differences in the area under the receiver operating characteristic curve (AUC) were used to compare the diagnostic performance of DS, LS, and a combination of DS and LS. Results There were 159 participants evaluated (among them, 79 participants with chronic hepatitis B and 11 participants with nonalcoholic fatty liver disease). The distributions of DS values among various necroinflammatory activities (P = .02) and fibrosis stages (P < .001) were different. Moreover, DS was only associated with fibrosis after subgroup analysis based on the fibrosis stages and necroinflammatory activities (P < .001). The AUCs of DS in detecting clinically significant fibrosis (fibrosis stage ≥F2), cirrhosis (fibrosis stage of F4), and moderate to severe necroinflammatory activity (necroinflammatory activity ≥A2) were 0.72 (95% CI: 0.64, 0.79), 0.71 (95% CI: 0.63, 0.78), and 0.64 (95% CI: 0.55, 0.71), respectively. The differences of AUCs were not apparent for the DS and LS combination model after excluding DS (fibrosis stage ≥F2: 0.00 [95% CI: 0.00, 0.01], fibrosis stage of F4: -0.01 [95% CI: -0.02, 0.00], and necroinflammatory activity ≥A2: 0.00 [95% CI: 0.00, 0.01]). Conclusion The addition of dispersion slope derived from two-dimensional shear-wave elastography did not improve the diagnostic performance in detecting liver fibrosis, necroinflammation, or steatosis in patients with primarily viral hepatitis. ClinicalTrials.gov registration no.: NCT03777293 © RSNA, 2022 Online supplemental material is available for this article.

Identification of an Iron Metabolism-Related lncRNA Signature for Predicting Osteosarcoma Survival and Immune Landscape.

Background: Long noncoding RNAs (lncRNAs) act as epigenetic regulators in the process of ferroptosis and iron metabolism. This study aimed to identify an iron metabolism-related lncRNA signature to predict osteosarcoma (OS) survival and the immune landscape. Methods: RNA-sequencing data and clinical information were obtained from the TARGET dataset. Univariate Cox regression and LASSO Cox analysis were used to develop an iron metabolism-related lncRNA signature. Consensus clustering analysis was applied to identify subtype-based prognosis-related lncRNAs. CIBERSORT was used to analyze the difference in immune infiltration and the immune microenvironment in the two clusters. Results: We identified 302 iron metabolism-related lncRNAs based on 515 iron metabolism-related genes. The results of consensus clustering showed the differences in immune infiltration and the immune microenvironment in the two clusters. Through univariate Cox regression and LASSO Cox regression analysis, we constructed an iron metabolism-related lncRNA signature that included seven iron metabolism-related lncRNAs. The signature was verified to have good performance in predicting the overall survival, immune-related functions, and immunotherapy response of OS patients between the high- and low-risk groups. Conclusion: We identified an iron metabolism-related lncRNA signature that had good performance in predicting survival outcomes and showing the immune landscape for OS patients. Furthermore, our study will provide valuable information to further develop immunotherapies of OS.