Three new triterpenoids from the fruit of Eleutherococcus senticosus (Rupr.) Harms.

A phytochemical investigation on the 70% EtOH extract of the fruit of Acanthpanax senticosus resulted in the isolation of three new triterpenoids, Falcatane C (1), Acasentrioid F (2), Acasentrioid G (3) together with twenty-seven known ones (4-30). Structural elucidation of all the compounds was performed by spectral methods such as 1D or 2D (1H-1H COSY, HSQC, and HMBC), NMR spectroscopy, and high-resolution mass spectrometry. Moreover, all compounds were evaluated for their effects on H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Ycells. Compounds 13 and 15 showed significant neuroprotective impact at a specific concentration, and compounds 1, 3, 5, 9, 11, 13-15, 17, 20-21, 23-25, 27, 29-30 showed moderate neuroprotective effect. The current study suggests that triterpenes in Eleutherococcus senticosus (Rupr.) Harms may play an essential role in the neuroprotective properties.

Tislelizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma in China: a cost-effectiveness analysis.

Objective: The goal of this study is to compare the cost-effectiveness of tislelizumab and sorafenib as first-line treatment for advanced hepatocellular carcinoma in China. Methods: A comprehensive cost-effectiveness analysis was undertaken within the framework of a partitioned survival model to accurately gage the incremental cost-effectiveness ratio (ICER) of tislelizumab compared to sorafenib. The model incorporated relevant clinical data and all survival rates were from RATIONALE-301 trials. The stability of the partitioned survival model was assessed by performing one-way and two-way sensitivity analyses. Results: The total cost incurred for the tislelizumab treatment was $16181.24, whereas the sorafenib was $14306.87. The tislelizumab regimen resulted in a significant increase of 0.18 quality-adjusted life years (QALYs) and an extra cost of $1874.37 as compared to chemotherapy. The ICER was $10413.17 per QALY, which was found to be below the willingness-to-pay (WTP) threshold of $37304.34/QALY. The results of the sensitivity analysis found that no fluctuations in any of the factors affected our results, even when these parameters fluctuated. Conclusion: Tislelizumab appears to be a cost-effective first-line treatment for advanced hepatocellular carcinoma when compared to sorafenib in China. These findings can inform decision-making processes regarding the selection of the most cost-effective treatment option for advanced hepatocellular carcinoma.

Targeting cellular senescence as a therapeutic vulnerability in gastric cancer.

AIMS: Cellular senescence (CS) represents an intracellular defense mechanism responding to stress signals and can be leveraged as a "vulnerability" in cancer treatment. This study aims to construct a CS atlas for gastric cancer (GC) and uncover potential therapeutics for GC patients. MATERIALS AND METHODS: 38 senescence-associated regulators with prognostic significance in GC were obtained from the CellAge database to construct Gastric cancer-specific Senescence Score (GSS). Using eXtreme Sum algorism, GSS-based drug repositioning was conducted to identify drugs that could antagonize GSS in CMap database. In vitro experiments were conducted to test the effect of combination of palbociclib and exisulind in eliminating GC cells. KEY FINDINGS: Patients with high GSS exhibited CS-related features, such as CS markers upregulation, adverse clinical outcomes and hypomethylation status. scRNA-seq data showed malignant cells with high GSS exhibited enhanced senescence state and more immunosuppressive signals such as PVR-CD96 compared with malignant cells with low GSS. In addition, the GSS-High cancer associated fibroblasts might secrete cytokines and chemokines such as IL-6, CXCL1, CXCL12, and CCL2 to from an immunosuppressive microenvironment, and GSS could serve as an indicator for immunotherapy resistance. Exisulind exhibited the greatest potential to reverse GSS. In vitro experiments demonstrated that exisulind could induce apoptosis and suppress the proliferation of palbociclib-induced senescent GC cells. SIGNIFICANCE: Overall, GSS offers a framework for better understanding of correlation between senescence and GC, which might provide new insights into the development of novel therapeutics in GC.

Seven new triterpenoids from the roots of Adenophora tetraphylla (Thub.) Fisch.

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.

Development of a Novel Contrast-Enhanced Ultrasound-Based Nomogram for Superficial Lymphadenopathy Differentiation: Postvascular Phase Value.

OBJECTIVE: The aim of this study was to develop and prospectively validate a prediction model for superficial lymphadenopathy differentiation using Sonazoid contrast-enhanced ultrasound (CEUS) combined with ultrasound (US) and clinical data. METHODS: The training cohort comprised 260 retrospectively enrolled patients with 260 pathological lymph nodes imaged between January and December 2020. Two clinical US-CEUS models were created using multivariable logistic regression analysis and compared using receiver operating characteristic curve analysis: Model 1 included clinical and US characteristics; Model 2 included all confirmed predictors, including CEUS characteristics. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) algorithm. Data from 172 patients were prospectively collected between January and May 2021 for model validation. RESULTS: Age, tumor history, long-axis diameter of lymph node, blood flow distribution, echogenic hilus, and the mean postvascular phase intensity (MPI) were identified as independent predictors for malignant lymphadenopathy. The area under the curve (AUC), sensitivity, specificity, and accuracy of MPI alone was 0.858 (95% confidence interval [CI], 0.817-0.891), 86.47%, 74.55%, and 81.2%, respectively. Model 2 had an AUC of 0.919 (95% CI, 0.879-0.949) and good calibration in training and validation cohorts. The incorporation of MPI significantly enhanced diagnostic capability (p < 0.0001 and p = 0.002 for training and validation cohorts, respectively). Decision curve analysis indicated Model 2 as the superior diagnostic tool. SHAP analysis highlighted MPI as the most pivotal feature in the diagnostic process. CONCLUSION: The employment of our straightforward prediction model has the potential to enhance clinical decision-making and mitigate the need for unwarranted biopsies.

Malignancy-associated ischemic stroke: Implications for diagnostic and therapeutic workup.

BACKGROUND: Patients with malignancies have an increased risk of suffering ischemic stroke via several mechanisms such as coagulation dysfunction and other malignancy-related effects as well as iatrogenic causes. Moreover, stroke can be the first sign of an occult malignancy, termed as malignancy-associated ischemic stroke (MAS). Therefore, timely diagnostic assessment and targeted management of this complex clinical situation are critical. FINDINGS: Patients with both stroke and malignancy have atypical ages, risk factors, and often exhibit malignancy-related symptoms and multiple lesions on neuroimaging. New biomarkers such as eicosapentaenoic acid and blood mRNA profiles may help in distinguishing MAS from other strokes. In terms of treatment, malignancy should not be considered a contraindication, given comparable rates of recanalization and complications between stroke patients with or without malignancies. CONCLUSION: In this review, we summarize the latest developments in diagnosing and managing MAS, especially stroke with occult malignancies, and provide new recommendations from recently emerged clinical evidence for diagnostic and therapeutic workup strategies.

Effects of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity and sexual function of cervical cancer survivors.

BACKGROUND: Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. METHODS: A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. RESULTS: Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. CONCLUSIONS: Cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment.

Cervical cancer survivors can experience vaginal condition deterioration and sexual dysfunction after treatment. Vaginal dilation can help improve vaginal stenosis, vaginal length and sexual function of these patients. However, some medical institutions in China do not provide timely vaginal dilation for this population. This study aimed to explore whether vaginal dilation was still effective for cervical cancer survivors who had not received timely vaginal dilation. The results showed that these patients still benefitted from vaginal dilation, irrespective of the treatment methods they received. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilation. The findings of the study is an indication to developing countries that more attention should be given to sexual issue of cervical cancer survivors in clinical practice, and vaginal dilation therapy should be performed promptly after treatment.

Differential diagnosis of cervical lymphadenopathy: Integration of postvascular phase of contrast-enhanced ultrasound and predictive nomogram model.

BACKGROUND: Distinguishing benign from malignant cervical lymph nodes is critical yet challenging. This study evaluates the postvascular phase of contrast-enhanced ultrasound (CEUS) and develops a user-friendly nomogram integrating demographic, conventional ultrasound, and CEUS features for accurate differentiation. METHODS: We retrospectively analyzed 395 cervical lymph nodes from 395 patients between January 2020 and December 2022. The cohort was divided into training and validation sets using stratified random sampling. A predictive model, based on demographic, ultrasound, and CEUS features, was created and internally validated. RESULTS: The training set included 280 patients (130 benign, 150 malignant nodes) and the validation set 115 patients (46 benign, 69 malignant). Relative hypoenhancement in the postvascular phase emerged as a promising indicator for MLN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96.7 %,52.3 %, 70.0 %, 93.2 %, and 76.1 %, respectively in the training set and 95.7 %, 52.2 %, 75.0 %, 88.9 %, and 74.8 % in the validation set. Age over 50 years, history of malignancy, short-axis diameter greater than 1.00 cm, focal hyperechogenicity, ill-defined borders, and centripetal perfusion were also identified as independent MLN indicators. The nomogram prediction model showed outstanding accuracy, with an area under the curve (AUC) of 0.922 (95 % CI: 0.892-0.953) in the training set and 0.914 (95 % CI: 0.864-0.963) in the validation set. CONCLUSION: Relative hypoenhancement in the postvascular phase of CEUS, combined with demographics and ultrasound features, is effective for identifying MLNs. The developed prediction model, with a user-friendly nomogram, can facilitate clinical decision-making.

Accuracy of implant placement via dynamic navigation and autonomous robotic computer-assisted implant surgery methods: A retrospective study.

OBJECTIVE: Optimal implant planning and placement allows the prosthesis to be well designed to achieve a satisfactory aesthetic and functional outcome. We aimed to compare deviations between implant planning and placement with the assistance of dynamic computer-assisted implant surgery (d-CAIS) or autonomous robotic computer-assisted implant surgery (r-CAIS) methods in a clinical setting. METHODS: The retrospective analysis of medical records between 2021 July and 2022 December was conducted to compare the implantation accuracy of the d-CAIS and r-CAIS system in partially edentulous patients through cone-beam computed tomography. Patient-reported outcomes (PROs) were recorded using a visual analogue scale (VAS). The Kolmogorov-Smirnov test was used to check the data distribution. Student's t-test or Mann-Whitney U-test was used as appropriate, with a defined significant difference (p < .05). RESULTS: Seventy-seven patients were analysed (124 implants), with 38 patients (62 implants) in the d-CAIS group and 39 patients (62 implants) in the r-CAIS group. The differences between d-CAIS and r-CAIS were 4.09 ± 1.79° versus 1.37 ± 0.92° (p < .001) in angular deviation; 1.25 ± 0.54 versus 0.68 ± 0.36 mm (p < .001) in coronal global deviation; 1.39 ± 0.52 versus 0.69 ± 0.36 mm (p < .001) in apical global deviation; the results of the PROMs showed no statistical difference between the two groups. CONCLUSIONS: r-CAIS allows more accurate implant placement than the d-CAIS technology. And both groups achieved overall satisfactory outcomes via VAS (Chinese Clinical Trial Registry ChiCTR2300072004).

Effects of vaginal dilation therapy on vaginal condition and sexual function of endometrial cancer patients treated with radiotherapy after surgery.

OBJECTIVE: This study aimed to evaluate the effect of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity, and sexual function of endometrial cancer patients treated with radiotherapy after surgery. METHODS: A total of 117 women were enrolled in this study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal length, vaginal diameter, vaginal elasticity, and sexual function before radiotherapy, after radiotherapy, and after 6 months of vaginal dilation therapy. Their vaginal condition was assessed by customized vaginal dilating molds. Their sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyze all the data. RESULTS: According to multivariate analysis, vaginal diameter (ß = 0.300, 95% CI [0.217-1.446], p = 0.010) and sexual intercourse frequency before diagnosis (ß = 0.424, 95% CI [0.164-0.733], p = 0.006) were significantly correlated with female sexual function after radiotherapy. Vaginal dilation therapy helped increase vaginal length, improve vaginal stenosis and sexual function (p < 0.05), though most of the figures at the end of the intervention did not fully return to those before radiotherapy. Noticeably, vaginal dilation therapy was ineffective in improving vaginal elasticity and the incidence rate of female sexual dysfunction (p > 0.05). Moreover, patients with medium or good vaginal elasticity benefited more from vaginal dilation therapy than patients with poor vaginal elasticity (p < 0.05). CONCLUSION: Vaginal dilation therapy should be carried out timely and preventatively in endometrial cancer patients treated with radiotherapy after surgery to improve their vaginal condition and sexual function.

Deep learning models of ultrasonography significantly improved the differential diagnosis performance for superficial soft-tissue masses: a retrospective multicenter study.

BACKGROUND: Most of superficial soft-tissue masses are benign tumors, and very few are malignant tumors. However, persistent growth, of both benign and malignant tumors, can be painful and even life-threatening. It is necessary to improve the differential diagnosis performance for superficial soft-tissue masses by using deep learning models. This study aimed to propose a new ultrasonic deep learning model (DLM) system for the differential diagnosis of superficial soft-tissue masses. METHODS: Between January 2015 and December 2022, data for 1615 patients with superficial soft-tissue masses were retrospectively collected. Two experienced radiologists (radiologists 1 and 2 with 8 and 30 years' experience, respectively) analyzed the ultrasound images of each superficial soft-tissue mass and made a diagnosis of malignant mass or one of the five most common benign masses. After referring to the DLM results, they re-evaluated the diagnoses. The diagnostic performance and concerns of the radiologists were analyzed before and after referring to the results of the DLM results. RESULTS: In the validation cohort, DLM-1 was trained to distinguish between benign and malignant masses, with an AUC of 0.992 (95% CI: 0.980, 1.0) and an ACC of 0.987 (95% CI: 0.968, 1.0). DLM-2 was trained to classify the five most common benign masses (lipomyoma, hemangioma, neurinoma, epidermal cyst, and calcifying epithelioma) with AUCs of 0.986, 0.993, 0.944, 0.973, and 0.903, respectively. In addition, under the condition of the DLM-assisted diagnosis, the radiologists greatly improved their accuracy of differential diagnosis between benign and malignant tumors. CONCLUSIONS: The proposed DLM system has high clinical application value in the differential diagnosis of superficial soft-tissue masses.

Tejas functions as a core component in nuage assembly and precursor processing in Drosophila piRNA biogenesis.

PIWI-interacting RNAs (piRNAs), which protect genome from the attack by transposons, are produced and amplified in membraneless granules called nuage. In Drosophila, PIWI family proteins, Tudor-domain-containing (Tdrd) proteins, and RNA helicases are assembled and form nuage to ensure piRNA production. However, the molecular functions of the Tdrd protein Tejas (Tej) in piRNA biogenesis remain unknown. Here, we conduct a detailed analysis of the subcellular localization of fluorescently tagged nuage proteins and behavior of piRNA precursors. Our results demonstrate that Tej functions as a core component that recruits Vasa (Vas) and Spindle-E (Spn-E) into nuage granules through distinct motifs, thereby assembling nuage and engaging precursors for further processing. Our study also reveals that the low-complexity region of Tej regulates the mobility of Vas. Based on these results, we propose that Tej plays a pivotal role in piRNA precursor processing by assembling Vas and Spn-E into nuage and modulating the mobility of nuage components.

Low FNDC5/Irisin expression is associated with aggressive phenotypes in gastric cancer.

Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown. Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients. Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients. Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.

Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma.

Background: Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC. Methods: The expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database. Results: The mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients' prognosis in different subgroups of ccRCC. Conclusion: Our study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.

An Immune Signature for Risk Stratification and Therapeutic Prediction in Helicobacter pylori-Infected Gastric Cancer.

Helicobacter pylori (HP) infection is the greatest risk factor for gastric cancer (GC). Increasing evidence has clarified that tumor immune microenvironment (TIME) is closely related to the prognosis and therapeutic efficacy of HP-positive (HP+) GC patients. In this study, we aimed to construct a novel immune-related signature for predicting the prognosis and immunotherapy efficacy of HP+ GC patients. A total of 153 HP+ GC from three different cohorts were included in this study. An Immune-Related prognostic Signature for HP+ GC patients (IRSHG) was established using Univariate Cox regression, the LASSO algorithm, and Multivariate Cox regression. Univariate and Multivariate analyses proved IRSHG was an independent prognostic predictor for HP+ GC patients, and an IRSHG-integrated nomogram was established to quantitatively assessthe prognostic risk. The low-IRSHG group exhibited higher copy number load and distinct mutation profiles compared with the high-IRSHG group. In addition, the difference of hallmark pathways and immune cells infiltration between the two groups was investigated. Notably, tumor immune dysfunction and exclusion (TIDE) analysis indicated that the low-IRSHG group had a higher sensitivity to anti-PD-1 immunotherapy, which was validated by an external pabolizumab treatment cohort. Moreover, 98 chemotherapeutic drugs and corresponding potential biomarkers were identified for two groups, and several drugs with potential ability to reverse IRSHG score were identified using CMap analysis. Collectively, IRSHG may serve as a promising biomarker for survival outcome as well as immunotherapy efficacy. Furthermore, it can also help to prioritize potential therapeutics for HP+ GC patients, providing new insight for the personalized treatment of HP-infected GC.

A New Way Out of the Predicament of Anaplastic Thyroid Carcinoma From Existing Data Analysis.

Background: Anaplastic thyroid carcinoma (ATC) is an endocrine tumor with a low incidence but a very poor prognosis. The vast majority of patients have a survival time of only three to six months, but a few survive for two years or more. In recent years, there have been major breakthroughs in targeted and immunotherapy in the field of oncology therapy. Although the preliminary study for ATC showed a promising prospect, more clinical trials are needed. It is the best approach to explore the measures that can improve survival time of ATC from the available clinical data, especially those with long survival. Methods: We report on an 82-year-old ATC patient who survived for 3 years and systematically review the clinical characteristics of 45 ATC patients with complete data from the two largest centers in northwest China. In particular, factors related to long-term survival were analyzed and summarized. Results: Three years prior, an 82-year-old woman was diagnosed with ATC by core needle biopsy following a physical examination. The thyroid tumor was resected within one month, and then the patient was treated with radiotherapy. The patient was still healthy after three years of follow-up. Analysis of prognostic factors for the 45 reviewed patients showed that those undergoing radical surgery (median overall survival (OS) = 472 days, p = 0.0261) and radiotherapy (median OS = 220 days, p = 0.0136) had better outcomes. In addition, patients younger than 65 years (median OS = 164.5 days, p = 0.0176) and with a lower tumor stage (IV A, median OS = 633.5 days, p = 0.0191) also had a better outcome. Conclusion: ATC is a highly malignant tumor, but timely early diagnosis and standardized treatment with radical surgery and radiotherapy as the core can achieve good results. Some patients can achieve long-term survival.

Accuracy of conventional ultrasound, contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging in assessing the size of breast cancer.

OBJECTIVE: This study was performed to investigate the accuracy of conventional ultrasound (US), contrast-enhanced US (CEUS), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the size of breast cancer. METHODS: In total, 49 breast cancer lesions of 48 patients were included in this study. The inclusion criteria were the performance of total mastectomy or breast-conserving surgery for treatment of breast cancer in our hospital from January 2017 to December 2020 with complete pathological results, as well as the performance of conventional US, CEUS, and DCE-MRI examinations with complete results. The exclusion criteria were non-mass breast cancer shown on conventional US or DCE-MRI, including that found on CEUS with no boundary with surrounding tissues and no confirmed tumor scope; a tumor too large to be completely displayed in the US section, thus affecting the measurement results; the presence of two nodules in the same breast that were too close to each other to be distinguished by any of the three imaging methods; and treatment with preoperative chemotherapy. Preoperative conventional US, CEUS, and DCE-MRI examinations were performed. The postoperative pathological results were taken as the gold standard. The lesion size was represented by its maximum diameter. The accuracy, overestimation, and underestimation rates of conventional US, CEUS, and DCE-MRI were compared. RESULTS: The maximum lesion diameter on US, CEUS, DCE-MRI and pathology were 1.62±0.63 cm (range, 0.6-3.5 cm), 2.05±0.75 cm (range, 1.0-4.0 cm), 1.99±0.74 cm (range, 0.7-4.2 cm) and 1.92±0.83 cm (range, 0.5-4.0 cm), respectively. The lesion size on US was significantly smaller than that of postoperative pathological tissue (P < 0.05). However, there was no significant difference between the CEUS or DCE-MRI results and the pathological results. The underestimation rate of conventional US (55.1%, 27/49) was significantly higher than that of CEUS (20.4%, 10/49) and DCE-MRI (24.5%, 12/49) (P < 0.001 and P = 0.002, respectively). There was no significant difference in the accuracy of CEUS (36.7%, 18/49) and DCE-MRI (34.7%, 17/49) compared with conventional US (26.5%, 13/49); however, the accuracy of both groups tended to be higher than that of conventional US. The overestimation rate of CEUS (42.9%, 21/49) and DCE-MRI (40.8%, 20/49) was significantly higher than that of conventional US (18.4%, 9/49) (P = 0.001 and P = 0.015, respectively). CONCLUSIONS: CEUS and DCE-MRI show similar performance when evaluating the size of breast cancer. However, CEUS is more convenient, has a shorter operation time, and has fewer restrictions on its use. Notably, conventional US is more prone to underestimate the size of lesions, whereas CEUS and DCE-MRI are more prone to overestimate the size.

Thermal shielding performance of self-healing hydrogel in tumor thermal ablation.

Thermal ablation therapy is widely used in the surgical treatment of tumors. Clinically, normal saline is generally used as an insulator to protect adjacent tissues from local high-temperature burns caused by thermal ablation. However, the flow of saline causes fluid loss, requiring frequent injections and complex operation, which is easy to lead to complications such as secondary injury and hematoma. Here, a self-healing chitosan-PEG (CP) hydrogel was proposed as a protective medium to challenge the clinical preparations. Compared with saline and non-self-healing hydrogel F127, CP hydrogel exhibited outstanding thermal shielding performance in the thermal ablation of thyroid nodule in a Beagle dog model. The transient plane source (TPS) method is used to measure thermal properties, including thermal conductivity, thermal diffusivity and specific heat capacity. The thermal shielding mechanism and clinical advantages including operability, biodegradability, and biological safety of self-healing hydrogel are then revealed in-depth. Therefore, self-healing hydrogel can achieve much better thermal management in tumor thermal ablation.

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer.

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among the triggering receptors expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease-free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not in macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

Urban sediment pollutants alternate human cell essential behaviour through promoting oxidative damage.

The main objective of this study was to establish a human cell-based platform to assess the effects of sediment toxicity on oxidative damage and cell essential behaviour. Since sediment pollution has increased as a consequence of including but not limited to industrialisation, the contaminants accumulated in sediments have already led to human health concerns. The Hsinchu Science Park is one of the most prominent semiconductor manufacturing centres in the world, and the Ke-Ya River flows through Hsinchu Science Park and the Hsinchu urban district. Because semiconductor wastes potentially contribute to higher-than-normal rates of cancers, birth defects, and serious diseases, the quality assessment of the Ke-Ya River has prompted widespread concerns. While previous studies have shown an association between the degradation of fish populations and sediment pollutants, very little is known about the issues on human health. Herein, the effects of sediment from three sediment sampling sites of the Ke-Ya River on 11 different human cell lines were directly evaluated. The upstream represents the undeveloped zone, the middle-stream represents the household/industrial wastewater zone, and the downstream represents the accumulation zone. Our results indicated that the sediment pollution of the downstream Ke-Ya River was more cytotoxic than that of the middle stream and upstream. Downstream sediment extract (DSE) significantly increased reactive oxygen species (ROS) levels across all cell types. Accordingly, oxidative stress can trigger redox-sensitive pathways and alter essential biological processes such as cell viability, cell adhesion, and cell motility. Importantly, the MTT assay indicated that DSE significantly decreased the viability of brain, oral, lung, breast, liver, pancreatic, cervical, prostate, and colorectal cells. Furthermore, the adhesive ability and wound healing ability of most cells were greatly reduced in the presence of DSE compared to other conditions. Thus, this study shows the results of the first analyses completed on the sediment cytotoxicity in human cells, and stimulated ROS levels are crucial for cellular life. In future research, the detailed cause and effect mechanisms of the abundant ROS generated in DSE will be further investigated. We sincerely hope that our study provides a scientific basis for further investigations with a global perspective on public health challenges.