Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Clinical and imaging predictors for hemorrhagic transformation of acute ischemic stroke after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a common complication of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS). Our study aims to investigate the clinical and imaging predictors of HT and symptomatic intracranial hemorrhage (sICH) in patients who underwent EVT. METHODS: A retrospective analysis of 118 patients undergoing EVT for acute anterior circulation stroke was performed. Potential clinical and imaging predictors of all patients were collected and multivariate logistic regression was performed. The risk prediction system was constructed according to the multivariate logistic regression results. RESULTS: The incidence of HT and sICH after EVT were 46.6% and 15.3%, respectively. The multivariate logistic regression results showed that Alberta Stroke Program Early CT Score (ASPECTS) (p = .001, odds ratio [OR] = 0.367, 95% [confidence interval] CI, 0.201-0.670), collateral status (p<.001, OR = 0.117, 95% CI, 0.042-0.325), relative cerebral blood flow (CBF) ratio (p = .025, OR = 0.943, 95% CI, 0.895-0.993), and blood glucose on admission (p = .012, OR = 1.258, 95% CI, 1.053-1.504) were associated with HT. While for sICH, collateral circulation (p = .007, OR = 0.148, 95% CI, 0.037-0.589), ASPECTS (p = .033, OR = 0.510, 95% CI, 0.274-0.946), and blood glucose (p = .005, OR = 1.304, 95% CI, 1.082-1.573) were independent factors. The predictive model for HT after EVT was established, and the sensitivity and specificity of it were 90.9% and 79.4%, respectively, with the area under the curve of 90.0% (84.5%-95.4%). CONCLUSION: Collateral status, ASPECTS, relative CBF ratio, and blood glucose on admission were predictors for HT in AIS patients, while collateral status, ASPECTS, and blood glucose on admission were also predictors for sICH. In addition, the established predictive model showed good diagnostic value for prediction of HT after EVT.

Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives.

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field of cancer immunotherapy, owing to their excellent capacity to activate the innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration of the strategies employed to develop effective formulations for STING agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements in delivery systems based on lipids, natural/synthetic polymers, and proteins for STING agonists are summarized. The preparation methodologies of nanoprecipitation, self-assembly, and hydrogel, along with their advantages and disadvantages, are also discussed. Furthermore, the challenges and opportunities in developing next-generation STING agonist delivery systems are elaborated. This review aims to serve as a reference for researchers in designing novel and effective STING agonist delivery systems for cancer immunotherapy.

A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.

Background: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations' antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib. Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds. Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI). Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.

How Nanotherapeutic Platforms Play a Key Role in Glioma? A Comprehensive Review of Literature.

Glioblastoma (GBM), a highly aggressive form of brain cancer, is considered one of the deadliest cancers, and even with the most advanced medical treatments, most affected patients have a poor prognosis. However, recent advances in nanotechnology offer promising avenues for the development of versatile therapeutic and diagnostic nanoplatforms that can deliver drugs to brain tumor sites through the blood-brain barrier (BBB). Despite these breakthroughs, the use of nanoplatforms in GBM therapy has been a subject of great controversy due to concerns over the biosafety of these nanoplatforms. In recent years, biomimetic nanoplatforms have gained unprecedented attention in the biomedical field. With advantages such as extended circulation times, and improved immune evasion and active targeting compared to conventional nanosystems, bionanoparticles have shown great potential for use in biomedical applications. In this prospective article, we endeavor to comprehensively review the application of bionanomaterials in the treatment of glioma, focusing on the rational design of multifunctional nanoplatforms to facilitate BBB infiltration, promote efficient accumulation in the tumor, enable precise tumor imaging, and achieve remarkable tumor suppression. Furthermore, we discuss the challenges and future trends in this field. Through careful design and optimization of nanoplatforms, researchers are paving the way toward safer and more effective therapies for GBM patients. The development of biomimetic nanoplatform applications for glioma therapy is a promising avenue for precision medicine, which could ultimately improve patient outcomes and quality of life.

Smart Biomimetic Nanozymes for Precise Molecular Imaging: Application and Challenges.

New nanotechnologies for imaging molecules are widely being applied to visualize the expression of specific molecules (e.g., ions, biomarkers) for disease diagnosis. Among various nanoplatforms, nanozymes, which exhibit enzyme-like catalytic activities in vivo, have gained tremendously increasing attention in molecular imaging due to their unique properties such as diverse enzyme-mimicking activities, excellent biocompatibility, ease of surface tenability, and low cost. In addition, by integrating different nanoparticles with superparamagnetic, photoacoustic, fluorescence, and photothermal properties, the nanoenzymes are able to increase the imaging sensitivity and accuracy for better understanding the complexity and the biological process of disease. Moreover, these functions encourage the utilization of nanozymes as therapeutic agents to assist in treatment. In this review, we focus on the applications of nanozymes in molecular imaging and discuss the use of peroxidase (POD), oxidase (OXD), catalase (CAT), and superoxide dismutase (SOD) with different imaging modalities. Further, the applications of nanozymes for cancer treatment, bacterial infection, and inflammation image-guided therapy are discussed. Overall, this review aims to provide a complete reference for research in the interdisciplinary fields of nanotechnology and molecular imaging to promote the advancement and clinical translation of novel biomimetic nanozymes.

Atypical primary central nervous system lymphoma and glioblastoma: multiparametric differentiation based on non-enhancing volume, apparent diffusion coefficient, and arterial spin labeling.

OBJECTIVES: To evaluate the multiparametric diagnostic performance with non-enhancing tumor volume, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) to differentiate between atypical primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). METHODS: One hundred and fifty-eight patients with pathologically confirmed typical PCNSL (n = 59), atypical PCNSL (hemorrhage, necrosis, or heterogeneous contrast enhancement, n = 29), and GBM (n = 70) were selected. Relative minimum ADC (rADCmin), mean (rADCmean), maximum (rADCmax), and rADCmax-min (rADCdif) were obtained by standardization of the contralateral white matter. Maximum cerebral blood flow (CBFmax) was obtained according to the ASL-CBF map. The regions of interests (ROIs) were manually delineated on the inner side of the tumor to further generate a 3D-ROI and obtain the non-enhancing tumor (nET) volume. The area under the curve (AUC) was used to evaluate the diagnostic performance. RESULTS: Atypical PCNSLs showed significantly lower rADCmax, rADCmean, and rADCdif than that of GBMs. GBMs showed significantly higher CBFmax and nET volume ratios than that of atypical PCNSLs. Combined three-variable models with rADCmean, CBFmax, and nET volume ratio were superior to one- and two-variable models. The AUC of the three-variable model was 0.96, and the sensitivity and specificity were 90% and 96.55%, respectively. CONCLUSION: The combined evaluation of rADCmean, CBFmax, and nET volume allowed for reliable differentiation between atypical PCNSL and GBM. KEY POINTS: • Atypical PCNSL is easily misdiagnosed as glioblastoma, which leads to unnecessary surgical resection. • The nET volume, ADC, and ASL-derived parameter (CBF) were lower for atypical PCNSL than that for glioblastoma. • The combination of multiple parameters performed well (AUC = 0.96) in the discrimination between atypical PCNSL and glioblastoma.

Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer.

Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments.

GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues. Here, we discovered that the deficiency of glutathione peroxidase 4 (GPX4), an essential antioxidant peroxidase, led to the accumulation of phospholipid peroxides and resulted in a loss of motor neurons in spinal cords of ALS mice. Mutant human SOD1G93A transgenic mice were intrathecally injected with neuron-targeted adeno-associated virus (AAV) expressing GPX4 (GPX4-AAV) or phospholipid peroxidation inhibitor, ferrostatin-1. The results showed that impaired motor performance and neural loss induced by SOD1G93A toxicity in the lumbar spine were substantially alleviated by ferrostatin-1 treatment and AAV-mediated GPX4 delivery. In addition, the denervation of neuron-muscle junction and spinal atrophy in ALS mice were rescued by neural GPX4 overexpression, suggesting that GPX4 is essential for the motor neural maintenance and function. In comparison, conditional knockdown of Gpx4 in the spinal cords of Gpx4fl/fl mice triggered an obvious increase of phospholipid peroxides and the occurrence of ALS-like motor phenotype. Altogether, our findings underscore the importance of GPX4 in maintaining phospholipid redox homeostasis in the spinal cord and presents GPX4 as an attractive therapeutic target for ALS treatment.

Healthcare preferences of the general Chinese population in the hierarchical medical system: A discrete choice experiment.

Background: Chinese health insurance system faces resource distribution challenges. A patient-centric approach allows decision-makers to be keenly aware of optimized medical resource allocation. Objective: This study aims to use the discrete choice model to determine the main factors affecting the healthcare preferences of the general Chinese population and their weights in the three scenarios (chronic non-communicable diseases, acute infectious diseases, and major diseases). Methods: This study firstly identified the key factors affecting people's healthcare preferences through literature review and qualitative interviews, and then designed the DCE questionnaire. An online questionnaire produced by Lighthouse Studio (version 9.9.1) software was distributed to voluntary respondents recruited from mainland China's entire population from January 2021 to June 2021. Participants were required to answer a total of 21 questions of three scenarios in the questionnaire. The multinomial logit model and latent class model were used to analyze the collected data. Results: A total of 4,156 participants from mainland China were included in this study. The multinomial logit and latent class model analyses showed that medical insurance reimbursement is the most important attribute in all three disease scenarios. In the scenario of "non-communicable diseases," the attributes that participants valued were, from the most to the least, medical insurance reimbursement (45.0%), hospital-level (21.6%), distance (14.4%), cost (9.7%), waiting time (8.3%), and care provider (1.0%). As for willingness to pay (WTP), participants were willing to pay 204.5 yuan, or 1,743.8 yuan, to change from private hospitals or community hospitals to tertiary hospitals, respectively. Conclusions: This study explores the healthcare preferences of Chinese residents from a new perspective, which can provide theoretical reference for the refinement of many disease medical reimbursement policies, such as developing different reimbursement ratios for various common diseases and realizing rational configuration of medical resources.

Comparison and risk factors analysis of multiple breast cancer screening methods in the evaluation of breast non-mass-like lesions.

OBJECTIVE: To compare multiple breast cancer screening methods for evaluating breast non-mass-like lesions (NMLs), and investigate new best screening method for breast non-mass-like lesions and the value of the lexicon of ACR BI-RADS in NML evaluation. METHODS: This retrospective study examined 253 patients aged 24-68 years who were diagnosed with breast NMLs and described the lexicon of ACR BI-RADS from April 2017 to December 2019. All lesions were evaluated by HHUS, MG, and ABUS to determine BI-RADS category, and underwent pathological examination within six months or at least 2 years of follow-up. The sensitivity, specificity, accuracy, positive predictive values (PPV), and negative predictive values (NPV) of MG, HHUS and ABUS in the prediction of malignancy were compared. Independent risk factors for malignancy were assessed using non-conditional logistic regression. RESULTS: HHUS, MG and ABUS findings significantly differed between benign and malignant breast NML, including internal echo, hyperechoic spot, peripheral blood flow, internal blood flow, catheter change, peripheral change, coronal features of ABUS, and structural distortion, asymmetry, and calcification in MG. ABUS is superior to MG and HHUS in sensitivity, specificity, PPV, NPV, as well as in evaluating the necessity of biopsy and accuracy in identifying malignancy. MG was superior to HHUS in specificity, PPV, and accuracy in evaluating the need for biopsy. CONCLUSIONS: ABUS was superior to HHUS and MG in evaluating the need for biopsy in breast NMLs. Compared to each other, HHUS and MG had their own relative advantages. Internal blood flow, calcification, and coronal plane feature was independent risk factors in NMLs Management, and different screening methods had their own advantages in NML management. The lexicon of ACR BI-RADS could be used not only in the evaluation of mass lesions, but also in the evaluation of NML.

Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor.

Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.

Application of Convolution Neural Network Algorithm Based on Multicenter ABUS Images in Breast Lesion Detection.

Objective: This study aimed to evaluate a convolution neural network algorithm for breast lesion detection with multi-center ABUS image data developed based on ABUS image and Yolo v5. Methods: A total of 741 cases with 2,538 volume data of ABUS examinations were analyzed, which were recruited from 7 hospitals between October 2016 and December 2020. A total of 452 volume data of 413 cases were used as internal validation data, and 2,086 volume data from 328 cases were used as external validation data. There were 1,178 breast lesions in 413 patients (161 malignant and 1,017 benign) and 1,936 lesions in 328 patients (57 malignant and 1,879 benign). The efficiency and accuracy of the algorithm were analyzed in detecting lesions with different allowable false positive values and lesion sizes, and the differences were compared and analyzed, which included the various indicators in internal validation and external validation data. Results: The study found that the algorithm had high sensitivity for all categories of lesions, even when using internal or external validation data. The overall detection rate of the algorithm was as high as 78.1 and 71.2% in the internal and external validation sets, respectively. The algorithm could detect more lesions with increasing nodule size (87.4% in ≥10 mm lesions but less than 50% in <10 mm). The detection rate of BI-RADS 4/5 lesions was higher than that of BI-RADS 3 or 2 (96.5% vs 79.7% vs 74.7% internal, 95.8% vs 74.7% vs 88.4% external). Furthermore, the detection performance was better for malignant nodules than benign (98.1% vs 74.9% internal, 98.2% vs 70.4% external). Conclusions: This algorithm showed good detection efficiency in the internal and external validation sets, especially for category 4/5 lesions and malignant lesions. However, there are still some deficiencies in detecting category 2 and 3 lesions and lesions smaller than 10 mm.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging of Rat Brain With Acute Carbon Monoxide Poisoning.

Objectives: To evaluate the diagnostic and prognostic values of glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging as a quantitative method for pathogenetic research and clinical application of carbon monoxide (CO) poisoning-induced encephalopathy combined with the proton magnetic resonance spectroscopy (1H-MRS) and the related histopathological and behavioral changes. Methods: A total of 63 Sprague-Dawley rats were randomly divided into four groups. Group A (n = 12) was used for animal modeling verification; Group B (n = 15) was used for magnetic resonance molecular imaging, Group C (n = 15) was used for animal behavior experiments, and Group D (n = 21) was used for histopathological examination. All the above quantitative results were analyzed by statistics. Results: The peak value of carboxyhemoglobin saturation in the blood after modeling was 7.3-fold higher than before and lasted at least 2.5 h. The GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than the base values in CO poisoning rats (p < 0.05) and the 1H-MRS showed significant differences in the parietal lobe and hippocampus. In the Morris water maze tests, the average latency and distance were significantly prolonged in poisoned rats (p < 0.05), and the cumulative time was shorter and negatively correlated with GluCEST. Conclusion: The GluCEST imaging non-invasively reflects the changes of glutamate in the brain in vivo with higher sensitivity and spatial resolution than 1H-MRS. Our study implies that GluCEST imaging may be used as a new imaging method for providing a pathogenetic and prognostic assessment of CO-associated encephalopathy.

Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer.

Protein PDZ and LIM domain 3 (PDLIM3) is a cytoskeletal protein, colocalizing with α-actinin on the Z line of mature muscle fibers. It plays a key role in dilated cardiomyopathy (DCM), muscular dystrophy, and tumor progression. However, correlations between PDLIM3 expression, prognosis, and tumor-infiltrating immune cells in gastric cancer are unknown. Therefore, we leveraged the Oncomine, GEPIA, GEO, and HPA databases to evaluate PDLIM3 expression in tumors. We also quantified PDLIM3 expression in 15 matched pairs of gastric tumor and nontumor tissues by immunohistochemistry. The Kaplan-Meier method was employed to determine the relationship between PDLIM3 expression and clinical outcomes. GO and KEGG analyses were performed to illuminate the molecular mechanisms of action of PDLIM3. TIMER2.0 and GEPIA were applied to investigate correlations between PDLIM3 expression and gene marker subsets signifying immune infiltration, with TIMER2.0 exploring the correlations between PDLIM3 and related signaling pathways. Gastric cancer tissues were found to express more PDLIM3 than nontumor tissues. PDLIM3 overexpression was associated with shorter OS and PFS of gastric cancer patients (OS HR = 2.02, P = 9.8e - 10; PFS HR = 1.77, P = 7.5e - 06). PDLIM3 was also positively correlated with worse OS and PFS according to gastric cancer staging, Her-2 overexpression, differentiation grade, and Lauren classification. PDLIM3 was shown to be associated with immunological responses by GO, while it was related to PI3K/Akt signal pathways by KEGG analysis. Furthermore, increased PDLIM3 expression was significantly correlated with greater infiltration of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. PDLIM3 expression had significant positive correlations with a variety of immune marker subsets. Finally, correlations were found between PDLIM3 and crucial markers of signaling pathways involving PI3K/Akt and p38 MAPK. Thus, upregulation of PDLIM3 was significantly associated with poor prognosis, immune cell infiltration, and activation of two key signal pathways in gastric cancer. We propose that PDLIM3 could be used as a biomarker to predict prognosis and immune cell infiltration in gastric cancer.

Radiologic and Histopathologic Features of a Neck-Localised Follicular Dendritic Cell Sarcoma: A Case Report and Literature Review.

Follicular dendritic cell sarcoma (FDCS) is an uncommon tumour. The pathological features of FDCS have been extensively described in the literature, but there are few reports on its imaging features. A 48-year-old man presented at our hospital with a mass in the left submandibular region without associated oral complaints. Contrast-enhanced magnetic resonance imaging revealed a mass with smooth margins, and postoperative histopathological and immunohistochemical findings were consistent with FDCS. At present, our understanding of FDCS is still insufficient, and its diagnosis is dependent on pathological evaluation. We aim to provide a bit of information for clinicians to consider when they see these types of tumours. Key Words: Follicular dendritic cell sarcoma, Magnetic resonance imaging, Imaging features, Histopathology.

Case Report: Magnetic Resonance Imaging Features of Scrotal Angiomyofibroblastoma (AMF) With Pathologic Correlation.

Angiomyofibroblastoma (AMF) is a rare benign myofibroblastic tumor that mainly occurs in the genital tract of middle-aged female patients. However, it can also arise in the scrotum, spermatic cord, and bladder. We described, herein, a case of a 42-year-old patient who was admitted to our hospital with a left scrotal mass. Imaging examinations showed that the mass had abundant vessels and displayed obvious progressive intensification on enhanced MRI. The following histopathological and immunohistochemical studies led to the diagnosis of AMF. Here, we describe the magnetic resonance imaging findings of a case of scrotal AMF. We hope that the information can help radiologists to identify AMF.

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy.

Intratumoral immunotherapeutic hydrogel administration is emerging as an effective method for inducing a durable and robust antitumor immune response. However, scaffold hydrogels that can synergize with the loaded drugs, thus potentiating therapeutic efficacy, are limited. Here, we report a ternary hydrogel composed of polyvinyl alcohol (PVA), polyethylenimine (PEI)‒a cationic polymer with potential immunoactivation effects, and magnesium ions‒a stimulator of the adaptive immune response, which exhibits an intrinsic immunomodulation function of reversing the immunologically "cold" phenotype of a murine breast tumor to a "hot" phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel (PEIGel) encapsulating an immune checkpoint blockade (ICB) inhibitor‒anti-PD-L1 antibody (α-PDL1) exhibits synergistic effects resulting in elimination of primary tumors and remote metastases and prevention of tumor relapse after surgical resection. A preliminary mechanistic study revealed a probably hidden role of PEI in modulating the polyamine metabolism/catabolism of tumors to potentiate the immune adjuvant effect. These results deepen our understanding of the innate immune activation function of PEI and pave the way for harnessing PEI as an immune adjuvant for ICB therapy.

Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer.

Sonodynamics has emerged as a new potential therapy for breast cancer in recent years. However, GSH-mediated redox systems in cancer cells make them tolerable to oxidative stress-related therapy. Herein, in this study, with G6PD, the gatekeeper enzyme of the pentose phosphate pathway, as the regulative target, a self-assembled thermosensitive chitosan-pluronic hydrogel coloaded with ICG (sono-sensitive agent) and RRx-001 (IR@CPGel) was successfully prepared to enhance SDT through interference with redox homeostasis. Both in vitro and in vivo antitumor investigations verified that when integrated with sonodynamic therapy applied in breast cancer treatment, local administration of IR@CPgel could enhance ROS generation under LIFU irradiation and trigger the intrinsic apoptotic pathway of cancer cells, thus effectively inhibiting tumor growth in a safe manner. Moreover, RRx-001 may interfere with redox homeostasis in cancer cells by downregulating G6PD expression. Due to this redox imbalance, proapoptotic signals, such as P21 and P53, were enhanced, and metastasis-related signals, including MMP-2, ZEB1 and HIF-1α, were effectively reduced. Taken together, this work aimed to enhance the efficacy of sonodynamic therapy through local administration of self-assembled IR@CPGel to interfere with redox homeostasis and thus amplify the oxidative stress microenvironment in tumor tissues. In a word, this work provides a new strategy for the SDT enhancement in breast cancer therapy.