Correlation analysis between the quantitative parameters of iodine-131 single-photon emission computed tomography-computed tomography thyroid bed uptake and the efficacy of radioactive iodine adjuvant therapy for papillary thyroid cancer.

Background: Single-photon emission computed tomography-computed tomography (SPECT/CT) quantification has emerged as a valuable tool for assessing disease prognosis by accurately identifying and characterizing abnormal lesions with accumulated radionuclides. Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, and radioactive iodine (RAI) therapy is a standard treatment following total thyroidectomy. This study aimed to explore the potential utility the quantitative parameters of the thyroid bed under iodine-131 (I-131) SPECT/CT in the efficacy of RAI adjuvant therapy for patients with PTC. Methods: The retrospective cohort study enrolled 107 patients with PTC who underwent RAI adjuvant therapy from June 2020 to January 2023. Three days after the RAI adjuvant therapy, all patients underwent I-131 whole-body scans and SPECT/CT imaging. The quantitative parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and percent injected dose (%ID), were measured using image analysis software based on I-131 SPECT/CT thyroid bed uptake. Successful therapy was defined as inhibitory thyroglobulin (Tg) <0.2 ng/mL with negative thyroglobulin antibody (TgAb) and negative imaging examination 6 months after RAI adjuvant therapy. The relationship between the quantitative parameters and the treatment efficacy, in addition to the potential influencing factors, were analyzed. Results: The quantitative parameters from the successful group [SUVmax: median 6.15 g/mL, interquartile range (IQR) 2.34-13.80 g/mL; SUVmean: median 2.02 g/mL, IQR 0.89-4.93 g/mL; %ID: median 2.00%, IQR 1.00-4.00%] were significantly lower than those from the unsuccessful group (SUVmax: median 19.03 g/mL, IQR 5.31-45.10 g/mL, SUVmean 4.64 g/mL, IQR 2.07-19.05 g/mL; %ID: median 8.00%, IQR 3.00-18.00%) (SUVmax: Z=-3.755; SUVmean; Z=-3.671; %ID: Z=-4.070; all P values <0.001). SUVmax, SUVmean and %ID were positively correlated with the stimulated thyroglobulin (sTg) and inhibitory Tg at 6 months after RAI adjuvant therapy, respectively (all P values <0.001). SUVmax [odds ratio (OR) =1.045], SUVmean (OR =1.130), and %ID (OR =1.092) were predictive factors for the failure of RAI adjuvant therapy (all P values <0.001). Conclusions: Our study suggested that quantitative parameters (SUVmax, SUVmean, and %ID) derived from I-131 SPECT/CT imaging of the thyroid bed can serve as useful tools for predicting therapy outcomes following RAI adjuvant therapy.

Proteomics Study of Benzene Metabolite Hydroquinone Induced Hematotoxicity in K562 Cells.

Objective: Hydroquinone (HQ), one of the phenolic metabolites of benzene, is widely recognized as an important participant in benzene-induced hematotoxicity. However, there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods: In this study, we treated K562 cells with 40 µmol/L HQ for 72 h, examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring (PRM), and performed bioinformatics analysis to identify interaction networks. Results: One hundred and eighty-seven upregulated differentially expressed proteins (DEPs) and 279 downregulated DEPs were identified in HQ-exposed K562 cells, which were involved in neutrophil-mediated immunity, blood microparticle, and other GO terms, as well as the lysosome, metabolic, cell cycle, and cellular senescence-related pathways. Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways, we constructed the network of protein interactions and determined 6 DEPs (STAT1, STAT3, CASP3, KIT, STAT5B, and VEGFA) as main hub proteins with the most interactions, among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion: Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Analysis of factors influencing hospitalization cost of patients with distal radius fractures: an empirical study based on public traditional Chinese medicine hospitals in two cities, China.

BACKGROUND: Distal radius fractures (DRFs) have become a public health problem for all countries, bringing a heavier economic burden of disease globally, with China's disease economic burden being even more acute due to the trend of an aging population. This study aimed to explore the influencing factors of hospitalization cost of patients with DRFs in traditional Chinese medicine (TCMa) hospitals to provide a scientific basis for controlling hospitalization cost. METHODS: With 1306 cases of DRFs patients hospitalized in 15 public TCMa hospitals in two cities of Gansu Province in China from January 2017 to 2022 as the study object, the influencing factors of hospitalization cost were studied in depth gradually through univariate analysis, multiple linear regression, and path model. RESULTS: Hospitalization cost of patients with DRFs is mainly affected by the length of stay, surgery and operation, hospital levels, payment methods of medical insurance, use of TCMa preparations, complications and comorbidities, and clinical pathways. The length of stay is the most critical factor influencing the hospitalization cost, and the longer the length of stay, the higher the hospitalization cost. CONCLUSIONS: TCMa hospitals should actively take advantage of TCMb diagnostic modalities and therapeutic methods to ensure the efficacy of treatment and effectively reduce the length of stay at the same time, to lower hospitalization cost. It is also necessary to further deepen the reform of the medical insurance payment methods and strengthen the construction of the hierarchical diagnosis and treatment system, to make the patients receive reasonable reimbursement for medical expenses, thus effectively alleviating the economic burden of the disease in the patients with DRFs.

Immunohistochemical profile of triple negative breast cancers: SOX10 and AR dual negative tumors have worse outcomes.

Triple negative breast cancer (TNBC) refers to an estrogen receptor negative, progesterone receptor negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor (LAR) subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding post-neoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR, INPP4B), basal (SOX10, Nestin, CK5, EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, TRPS1) markers. Survival analysis was performed to assess the significance of clinical pathologic variables including age, histology, grade, lymphovascular invasion [LVI], Nottingham prognostic index [NPI] category, AJCC stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15 while no special type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on univariable as well as multivariable analysis. LVI and higher NPI category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage, and chemotherapy status.

Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene.

Millirobots must have low cost, efficient locomotion, and the ability to track target trajectories precisely if they are to be widely deployed. With current materials and fabrication methods, achieving all of these features in one millirobot remains difficult. We develop a series of graphene-based helical millirobots by introducing asymmetric light pattern distortion to a laser-induced polymer-to-graphene conversion process; this distortion resulted in the spontaneous twisting and peeling off of graphene sheets from the polymer substrate. The lightweight nature of graphene in combine with the laser-induced porous microstructure provides a millirobot scaffold with a low density and high surface hydrophobicity. Magnetically driven nickel-coated graphene-based helical millirobots with rapid locomotion, excellent trajectory tracking, and precise drug delivery ability were fabricated from the scaffold. Importantly, such high-performance millirobots are fabricated at a speed of 77 scaffolds per second, demonstrating their potential in high-throughput and large-scale production. By using drug delivery for gastric cancer treatment as an example, we demonstrate the advantages of the graphene-based helical millirobots in terms of their long-distance locomotion and drug transport in a physiological environment. This study demonstrates the potential of the graphene-based helical millirobots to meet performance, versatility, scalability, and cost-effectiveness requirements simultaneously.

The 21-Gene Recurrence Score Assay Improved Multidisciplinary Treatment Compliance in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: An Analysis of 2,323 Patients.

PURPOSE: The 21-gene recurrence score (RS) can guide adjuvant chemotherapy decisions in the multidisciplinary treatment (MDT) of patients with early breast cancer. This study aimed to evaluate the influence of the 21-gene RS assay on patient' compliance with MDT and its association with disease outcomes. METHODS: Patients diagnosed with pN0-1, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer between January 2013 and June 2019 were enrolled. A logistic regression model was used to identify parameters associated with treatment adherence. Prognostic indicators were evaluated using the Cox proportional hazard models. RESULTS: After the assay, patients were less likely to violate the treatment plan (14.9% vs. 23.1%, p < 0.001), and higher compliance rates were observed for chemotherapy (p = 0.042), radiotherapy (p = 0.012), and endocrine therapy (p < 0.001). Multivariable analysis demonstrated that the 21-gene RS assay (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.09-1.88; p = 0.009) was independently associated with MDT compliance. Moreover, compliance with MDT was independently associated with better disease-free survival (hazard ratio, 0.43; 95% CI, 0.29-0.64; p < 0.001), regardless of the 21-gene RS assay (interaction p = 0.842). CONCLUSION: The 21-gene RS assay improved the MDT compliance rate in patients with early breast cancer. Adherence to MDT is associated with a better prognosis.

LINC00173 silence and estrone supply suppress ER+ breast cancer by estrogen receptor α degradation and LITAF activation.

Persistent activation of estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in driving the progression of estrogen receptor positive (ER+) breast cancer (BC). In the current study, LINC00173, a long non-coding RNA, was found to bind both ERα and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFα) factor (LITAF), then cooperatively to inhibit ERα protein degradation by impeding the nuclear export of ERα. Concurrently, LITAF was found to attenuate TNFα transcription after binding to LINC00173, and this attenuating transcriptional effect was quite significant under lipopolysaccharide stimulation. Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF-transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression.

Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis.

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.

Epidural dexmedetomidine or esketamine versus fentanyl to decrease ropivacaine use for labor analgesia: A randomized non-inferiority study.

Background: Epidural nonopioid adjuvants also reduce local anesthetic use. We aimed to test the hypothesis that, compared with the present standard fentanyl, the hourly consumption of local anesthetic was at least as good when dexmedetomidine or esketamine was combined with local anesthetic for patient-controlled epidural analgesia (PCEA). Methods: A total of 120 laboring nulliparous subjects requiring labor analgesia were recruited for the final statistical analysis. Subjects were randomized to receive 0.075 % ropivacaine added with one of three equivalent adjuvants: 0.4 µg/mL fentanyl, 0.4 µg/mL dexmedetomidine, or 1.0 mg/mL esketamine. The primary outcome was hourly ropivacaine consumption. Compared with the fentanyl group, a 20 % difference in hourly local anesthetic consumption between the dexmedetomidine and esketamine groups was considered a clinical difference (non-inferiority margin). Results: The hourly ropivacaine consumption of the fentanyl group was 12.4 (95 % confidence interval CI 11.2 to 13.6) ml/h, so the prespecified non-inferiority limit was 2.5 ml/h. The hourly ropivacaine consumption of the fentanyl group was not inferior to that of the dexmedetomidine group (12.4 ml/h vs. 11.9 ml/h, risk difference, 0.5; 95 % confidence interval CI, -1.0 to 2.0, meeting criteria for non-inferiority). However, the hourly ropivacaine consumption of the esketamine group was 14.3 ml/h, and that of the fentanyl group was 12.4 ml/h (risk difference, 1.9, 95 % CI, 0.2 to 3.6), failing to confirm non-inferiority with a non-inferiority margin of 20 %. The incidence of pruritus was highest in the fentanyl group, whereas the occurrence of mild dizziness was highest in the esketamine group. Conclusions: In setting of the conditions of this study, epidural dexmedetomidine was non-inferior compared with epidural fentanyl in combination with ropivacaine for PCEA during labor. Meanwhile, we failed to establish the non-inferiority of epidural esketamine compared with epidural fentanyl in combination with ropivacaine for labor analgesia.

Tungsten phosphide on nitrogen and phosphorus-doped carbon as a functional membrane coating enabling robust lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) hold great potential as future energy storage technology, but their widespread application is hampered by the slow polysulfide conversion kinetics and the sulfur loss during cycling. In this study, we detail a one-step approach to growing tungsten phosphide (WP) nanoparticles on the surface of nitrogen and phosphorus co-doped carbon nanosheets (WP@NPC). We further demonstrate that this material provides outstanding performance as a multifunctional separator in LSBs, enabling higher sulfur utilization and exceptional rate performance. These excellent properties are associated with the abundance of lithium polysulfide (LiPS) adsorption and catalytic conversion sites and rapid ion transport capabilities. Experimental data and density functional theory calculations demonstrate tungsten to have a sulfophilic character while nitrogen and phosphorus provide lithiophilic sites that prevent the loss of LiPSs. Furthermore, WP regulates the LiPS catalytic conversion, accelerating the Li-S redox kinetics. As a result, LSBs containing a polypropylene separator coated with a WP@NPC layer show capacities close to 1500 mAh/g at 0.1C and coulombic efficiencies above 99.5 % at 3C. Batteries with high sulfur loading, 4.9 mg cm-2, are further produced to validate their superior cycling stability. Overall, this work demonstrates the use of multifunctional separators as an effective strategy to promote LSB performance.

Developing a machine learning model for predicting venlafaxine active moiety concentration: a retrospective study using real-world evidence.

BACKGROUND: Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary. AIM: Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques. METHOD: Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations. RESULTS: A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value. CONCLUSION: The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice.

PSA: an effective method for predicting horizontal gene transfers through parsimonious phylogenetic networks.

Horizontal gene transfer (HGT) from one organism to another, according to some researchers, can be abundant in the evolution of species. A phylogenetic network is a network structure that describes the HGTs among species. Several studies have proposed methods to construct phylogenetic networks to predict HGTs based on parsimony values. Existing definitions of parsimony values for a phylogenetic network are based on the assumption that each gene site or segment evolves independently along different trees in the network. However, in the current study, we define a novel parsimony value, denoted the p definition, for phylogenetic networks, considering that a gene as a whole typically evolves along a tree. Using Simulated Annealing, a new method called the Phylogeny with Simulated Annealing (PSA) algorithm is proposed to search for an optimal network based on the p definition. The PSA method is tested on the simulated data. The results reveal that the parsimonious networks constructed using PSA can better represent the evolutionary relationships of species involving HGTs. Additionally, the HGTs predicted using PSA are more accurate than those predicted using other methods. The PSA algorithm is publicly accessible at http://github.com/imustu/sap.

Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-ß-catenin complex and downregulation of SOX9.

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Enhancing Electric Field Distribution in the Pancreas for Improved TTFields Therapy: A Computational Modeling Investigation.

BACKGROUND: Tumor treating fields (TTFields) therapy has shown effectiveness in glioblastoma treatment and holds potential for other cancers. However, its application in pancreatic cancer and the distribution of electric fields in pancreas remain unexplored. This study aims to investigate the electric field distributions in pancreatic regions using different array configurations for TTFields therapy. METHODS: Computational modelling was employed to simulate electric field distributions, and quantitative analysis was conducted. Human body impedance measurements were used to optimize the electric properties of the model. Various array configurations were examined to assess their impact on the electric field distributions. RESULTS: The study revealed that well-positioned arrays, specifically the combination of 20-piece transducer arrays in anterior-posterior orientation and 13-piece transducer arrays in left-right orientation, consistently achieved electric fields exceeding the 1V/cm threshold in over 99.4% of the pancreas. Even with a reduced number of transducers (13 pieces for both orientations), sufficient electric field coverage was achieved, exceeding the threshold in over 92.9% of the pancreas. Additionally, different array placements within the same orientation were explored to address clinical challenges such as skin rash and patient anatomical variations. CONCLUSIONS: This research lays the groundwork for understanding TTFields distribution within the abdomen, offering insights into optimizing array configurations for improved electric field delivery. The findings have the potential to guide practical designs of TTFields devices, enhance treatment efficacy, and improve patient outcomes. These results offer promises of advancing TTFields therapy for pancreatic cancer towards clinical applications, and potentially enhancing treatment efficacy and patient outcomes.

Metastatic clear cell sarcoma of the pancreas: A rare case report.

BACKGROUND: Clear cell sarcoma (CCS) is a rare soft-tissue sarcoma. The most common metastatic sites for CCS are the lungs, bones and brain. CCS is highly invasive and mainly metastasizes to the lung, followed by the bone and brain; however, pancreatic metastasis is relatively rare. CASE SUMMARY: We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man. The patient had a relevant medical history 3 years ago, with abdominal pain as the main clinical manifestation. No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography. Based on the medical history and postoperative pathology, the patient was diagnosed with CCS with pancreatic metastasis. The patient was successfully treated with surgical interventions, including distal pancreatectomy and splenectomy. CONCLUSION: This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

Background: There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. Methods: From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. Results: The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). Conclusion: The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.