White and Gray Matter Abnormalities in Young Adult Females with Dependent Personality Disorder: A Diffusion-Tensor Imaging and Voxel-Based Morphometry Study.

We applied diffusion-tensor imaging (DTI) including measurements of fractional anisotropy (FA), a parameter of neuronal fiber integrity, mean diffusivity (MD), a parameter of brain tissue integrity, as well as voxel-based morphometry (VBM), a measure of gray and white matter volume, to provide a basis to improve our understanding of the neurobiological basis of dependent personality disorder (DPD). DTI was performed on young girls with DPD (N = 17) and young female healthy controls (N = 17). Tract-based spatial statistics (TBSS) were used to examine microstructural characteristics. Gray matter volume differences between the two groups were investigated using voxel-based morphometry (VBM). The Pearson correlation analysis was utilized to examine the relationship between distinct brain areas of white matter and gray matter and the Dy score on the MMPI. The DPD had significantly higher fractional anisotropy (FA) values than the HC group in the right retrolenticular part of the internal capsule, right external capsule, the corpus callosum, right posterior thalamic radiation (include optic radiation), right cerebral peduncle (p < 0.05), which was strongly positively correlated with the Dy score of MMPI. The volume of gray matter in the right postcentral gyrus and left cuneus in DPD was significantly increased (p < 0.05), which was strongly positively correlated with the Dy score of MMPI (r1,2= 0.467,0.353; p1,2 = 0.005,0.04). Our results provide new insights into the changes in the brain structure in DPD, which suggests that alterations in the brain structure might implicate the pathophysiology of DPD. Possible visual and somatosensory association with motor nerve circuits in DPD.

Clinical application of optical and electromagnetic navigation system in CT-guided radiofrequency ablation of lung metastases.

PURPOSE: To evaluate the clinical value of CT-guided radiofrequency ablation (RFA) in the diagnosis and treatment of pulmonary metastases under optical and electromagnetic navigation. METHODS: Data on CT-guided radiofrequency ablation treatment of 93 metastatic lung lesions in 70 patients were retrospectively analyzed. There were 46 males and 24 females with a median age of 60.0 years (16-85 years). All lesions were ≤3cm in diameter. 57 patients were treated with 17 G radiofrequency ablation needle puncture directly ablated the lesion without biopsy, and 13 patients were treated with 16 G coaxial needle biopsy followed by radiofrequency ablation. There were 25 cases in the optical navigation group, 25 in the electromagnetic navigation group, and 20 in the non-navigation group. The navigation group was performed by primary interventionalists with less than 5 years of experience, and the non-navigation group was performed by interventionalists with more than 5 years of experience. RESULT: All operations were successfully performed. There was no statistically significant difference in the overall distribution of follow-up results among the optical, electromagnetic, and no navigation groups. Complete ablation was achieved in 84 lesions (90.3%). 7 lesions showed incomplete ablation and were completely inactivated after repeat ablation. 2 lesions progressed locally, and one of them still had an increasing trend after repeat ablation. No serious complications occurred after the operation. CONCLUSIONS: Treatment with optical and electromagnetic navigation systems by less experienced operators has similar outcomes to traditional treatments without navigational systems performed by more experienced operators.

Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.

BACKGROUND AND PURPOSE: Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear. METHODS: Twenty-six patients exhibiting significant recovery after subcortical infarctions were investigated using multimodal MRI techniques. Structural impairment was assessed via cortical thickness, and functional reorganization was analyzed using task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity. RESULTS: Compared with healthy controls, patients with stroke exhibited reduced cortical thickness in the ipsilesional M1; however, this region exhibited increased task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity in these patients. Patients with stroke demonstrated increased task-evoked activation in another ipsilesional M1 region, in which increased amplitude of low-frequency fluctuation and resting-state functional connectivity were observed. The structural and functional changes in M1 were located selectively in the ipsilesional hemisphere. CONCLUSIONS: We provide convincing evidence that indicates extensive functional reorganization in the ipsilesional M1 of patients with chronic subcortical infarctions, including the structurally impaired M1 region.

CircSCUBE3 Reduces the Anti-gastric Cancer Activity of Anti-PD-L1.

The progression of gastric cancer (GC) is closely related to tumor immune escape. The research, therefore, studied the impact of possible circRNAs on the immune escape of GC tumors and the underlying mechanisms. Here, to explore circRNAs that may affect GC, the differential circRNAs in six normal gastric mucosal tissues and six GC samples (GSM2005868-GSM2005879) were analyzed through the bioinformatics website circmine, and hsa_circ_0076092 (circSCUBE3) was identified as the research object. In vitro assays revealed the functions of circSCUBE3 and its downstream miRNA/mRNA axis in GC cells. The effect of circSCUBE3 against PD-1 anti-tumor activity was evaluated in vivo. The relationship between circSCUBE3 and miR-744-5p, miR-744-5p, and SLC7A5 was identified by RNA immunoprecipitation and dual-luciferase reporter experiments. The effect of SLC7A5 on GC immune escape by regulating PD-L1 expression was assessed by co-culture system and flow cytometry. CircSCUBE3 was up-regulated in human GC tissues and GC cell lines. circSCUBE3 was associated with poor prognosis in GC patients. Functional experiments reported that circSCUBE3 knockdown could suppress GC immune escape. Mechanistically, circSCUBE3 bound to miR-744-5p, which further targeted SLC7A5, and SLC7A5 can affect GC immune escape by regulating PD-L1. Furthermore, in vivo assay manifested that circSCUBE3 attenuated the anti-tumor effect of PD-L1. Our study revealed the importance of the circSCUBE3/miR-744-5p/SLC7A5 axis in GC immune escape and anti-PD-1 resistance.

Altered functional connectivity of cognitive-related cerebellar subregions in well-recovered stroke patients.

The cerebellum contains several cognitive-related subregions that are involved in different functional networks. The cerebellar crus II is correlated with the frontoparietal network (FPN), whereas the cerebellar IX is associated with the default-mode network (DMN). These two networks are anticorrelated and cooperatively implicated in cognitive control, which may facilitate the motor recovery in stroke patients. In the present study, we aimed to investigate the resting-state functional connectivity (rsFC) changes in 25 subcortical ischemic stroke patients with well-recovered global motor function. Consistent with previous studies, the crus II was correlated with the FPN, including the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex, and the cerebellar IX was correlated with the DMN, including the posterior cingulate cortex/precuneus (PCC/Pcu), medial prefrontal cortex (MPFC), DLPFC, lateral parietal cortices, and anterior temporal cortices. No significantly increased rsFCs of these cerebellar subregions were found in stroke patients, suggesting that the rsFCs of the cognitive-related cerebellar subregions are not the critical factors contributing to the recovery of motor function in stroke patients. The finding of the disconnection in the cerebellar-related cognitive control networks may possibly explain the deficits in cognitive control function even in stroke patients with well-recovered global motor function.

Progress in the cryoablation and cryoimmunotherapy for tumor.

With the rapid advancement of imaging equipment and minimally invasive technology, cryoablation technology is being used more frequently in minimally invasive treatment of tumors, primarily for patients with early tumors who voluntarily consent to ablation as well as those with advanced tumors that cannot be surgically removed or cannot be tolerated. Cryoablation is more effective and secure for target lesions than other thermal ablation methods like microwave and radiofrequency ablation (RFA). The study also discovered that cryoablation, in addition to causing tumor tissue necrosis and apoptosis, can facilitate the release of tumor-derived autoantigens into the bloodstream and activate the host immune system to elicit beneficial anti-tumor immunological responses against primary. This may result in regression of the primary tumor and distant metastasis. The additional effect called " Accompanying effects ". It is the basis of combined ablation and immunotherapy for tumor. At present, there is a lot of research on the mechanism of immune response induced by cryoablation. Trying to solve the question: how positively induce immune response. In this review, we focus on: 1. the immune effects induced by cryoablation. 2. the effect and mechanism of tumor immunotherapy combined with cryoablation. 3.The clinical research of this combination therapy in the treatment of tumors.

Development and Validation of an Algorithm Model for Predicting Heat Sink Effects during Pulmonary Thermal Ablation

AIMS: The aim of this study was to develop an algorithm model to predict the heat sink effect during thermal ablation of lung tumors and to assist doctors in the formulation and adjustment of surgical protocols. BACKGROUND: The heat sink effect is an important factor affecting the therapeutic effect of tumor thermal ablation. At present, there is no algorithm model to predict the intraoperative heat sink effect automatically, which needs to be measured manually, which lacks accuracy and consumes time. OBJECTIVE: To construct a segmentation model based on a convolutional neural network that can automatically identify and segment pulmonary nodules and vascular structure and measure the distance between the nodule and vascular. METHODS: First, the classical Faster RCNN model was used as the nodule detection network. After obtaining the bounding box of pulmonary nodules, the VSPP-NET model was used to segment nodules in the bounding box. The distance from the nodule to the vasculature was measured after the surrounding vasculature was segmented by the VSPP-NET model. The lung CT images of 392 patients with pulmonary nodules were used as the training data for the algorithm. 68 cases were used as algorithm validation data, 29 as nodule algorithm test data, and 80 as vascular algorithm test data. We compared the heat sink effect of 29 cases of data with the results of the algorithm model and expert segmentation and compared the difference between the two results. RESULTS: In pulmonary CT image vasculature segmentation, the recall and precision of the algorithm model reached >0.88 and >0.78, respectively. The average time for automatic segmentation of each image model is 29 seconds, and the average time for manual segmentation is 158 seconds. The output image of the model shows that the results of nodule segmentation and nodule distance measurement are satisfactory. In terms of heat sink effect prediction, the positive rate of the algorithm group was 28.3%, and that of the expert group was 32.1%, with no significant difference between the two groups (p=0.687). CONCLUSION: The algorithm model developed in this study shows good performance in predicting the heat sink effect during pulmonary thermal ablation. It can improve the speed and accuracy of nodule and vessel segmentation, save ablation planning time, reduce the interference of human factors, and provide more reference information for surgeons to make ablation plans to improve the ablation effect.

An in situ thermal cross-linking binder for silicon-based lithium ion battery.

Silicon has been regarded as one of the most promising anode materials for lithium-ion batteries (LIBs) due to its highest specific capacity and low (de)lithiation potential, however, the development of practical applications for silicon are still hindered by devastating volume expansion and low conductance. Herein, we have proposed an in situ thermally cross-linked water-soluble PA@PAA binder for silicon-based LIBs to construct dynamic cross-linking network. Specifically, ester bonds between -P-OH in phytic acid (PA) and -COOH in PAA, which are generated by thermal coupling, are designed to synergize with hydrogen bonds between the PA@PAA binder and silicon particles to dissipate the high mechanical stresses, which is verified by theoretical calculation. GO is further adopted to protect silicon particles from immediate contact with electrolyte to improve initial coulombic efficiency (ICE). A range of heat treatment temperatures is explored to optimize the previous process conditions and the optimum electrochemical performance is provided by Si@PA@PAA-220 electrodes with high reversible specific capacity of 1322.1 mAh/g at a current density of 0.5A/g after 510 cycles. Characterization has also revealed that PA@PAA is involved in electrochemical process and tunes the ratio of organic (LixPFy/LixPOyFZ)-inorganic (LiF) to consolidate solid electrolyte interface (SEI) during cycles. In brief, this applicable fascial in situ strategy can effectively improve the stability of silicon anodes for high energy density lithium-ion batteries.

DNA Damage Inducer Mitoxantrone Amplifies Synergistic Mild-Photothermal Chemotherapy for TNBC via Decreasing Heat Shock Protein 70 Expression.

Patients with triple-negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology-assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO-micelles) is developed to realize mutually synergistic mild-photothermal chemotherapy. MTO with excellent near-infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO-micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near-infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO-micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild-photothermal chemotherapy strategy based on MTO-micelles has a promising prospect in the clinical transformation of TNBC treatment.

Chemo-immunoablation of solid tumors: A new concept in tumor ablation.

Chemical ablation was designed to inject chemical agents directly into solid tumors to kill cells and is currently only used clinically for the palliative treatment of tumors. The application and combination of different drugs, from anhydrous ethanol, and glacial acetic acid to epi-amycin, have been clinically tested for a long time. The effectiveness is unsatisfactory due to chemical agents' poor diffusion and concentration. Immunotherapy is considered a prospective oncologic therapeutic. Still, the clinical applications were limited by the low response rate of patients to immune drugs and the immune-related adverse effects caused by high doses. The advent of intratumoral immunotherapy has well addressed these issues. However, the efficacy of intratumoral immunotherapy alone is uncertain, as suggested by the results of preclinical and clinical studies. In this study, we will focus on the research of immunosuppressive tumor microenvironment with chemoablation and intratumoral immunotherapy, the synergistic effect between chemotherapeutic drugs and immunotherapy. We propose a new concept of intratumoral chemo-immunoablation. The concept opens a new perspective for tumor treatment from direct killing of tumor cells while, enhancing systemic anti-tumor immune response, and significantly reducing adverse effects of drugs.

Case report: Radiofrequency ablation combined with biopsy for Cushing's syndrome due to ectopic ACTH lesions in the lung.

Lung carcinoid tumor is one of the major tumors causing ectopic ACTH syndrome, and the most common clinical treatment is surgical resection of the lesion. We herein report a suspected pulmonary carcinoid tumor with difficulty in surgical resection and poor response to drug therapy, which was successfully treated with radiofrequency ablation combined with intraoperative biopsy of the lesion. A 48-year-old female patient, with hypercortisolism (reddening of the face, full moon face, hirsutism, acne, and weight gain) detected three months ago. Small and high-dose dexamethasone suppression tests were not suppressed, Cushing's syndrome was under consideration. PET-CT examination suggested mild FDG uptake in two nodules in the anterior basal segment of the lower lobe of the right lung, the possibility of ectopic ACTH lesions was considered because of the clinical presentation. Due to difficult surgical approach of the lesion, high risk of surgery and the patient's anxiety, CT-guided thermal ablation combined with puncture biopsy was considered to treat the lesions. Image-guided thermal ablation can effectively inactivate ectopic ACTH lesions in the lung, rapidly improve the symptoms of high cortisol, and can be combined with biopsy for pathologic diagnosis. Therefore, this technique can be considered for treating pulmonary ACTH lesions that are difficult to resect surgically.

Case report: Local cryoablation combined with pembrolizumab to eliminate lung metastases from ovarian clear cell carcinoma.

Ovarian clear cell carcinoma has a high recurrence rate with poor prognosis and is generally not sensitive to conventional platinum-based chemotherapy. Its less frequent occurrence of mutations such as BRCA limited the targeted therapies. Immunotherapy is not currently recommended as a first-line agent for ovarian cancer, and most patients are not yet able to benefit from it. Cryoablation can be used to treat solid systemic tumors, including ovarian cancer metastases, and can produce a limited anti-tumor immune response. The anti-tumor effects of cryoablation combined with immunotherapy have not been adequately confirmed. This study reports a case of a patient with ovarian clear cell carcinoma who underwent conventional adjuvant chemotherapy after initially surgical resection of the tumor. Unfortunately, cancer recurred and metastasized to the abdominal wall. After a series of painful chemotherapy and a second surgery, the cancer was still not effectively controlled, and the patient developed extensive metastases in the lung. The patient's PD-L1 expression level also did not support solo immunotherapy. We pioneered the use of cryoablation to first eradicate the most significant lesion in the upper lobe of the left lung and then combined it with the PD-L1 inhibitor pembrolizumab to treat the patient with immunotherapy, which resulted in the complete eradication of the other multiple metastases in the lung and saved the patient's life. Although the precise mechanism of action has not yet been explored, we have reason to believe that the combination of cryoablation and immune checkpoint inhibitor has a powerful synergistic anti-tumor effect, which is yet to be confirmed by more basic research and clinical applications in the next step.

Interaction of RARRES1 with ICAM1 modulates macrophages to suppress the progression of kidney renal clear cell carcinoma.

Background: RARRES1 is a tumor suppressor protein, and its expression is suppressed in various tumor cells. However, whether it participates in the immune response in kidney renal clear cell carcinoma (KIRC) is unknown, and the defined mechanism is not clear. Therefore, the mechanism of RARRES1 in KIRC is worthy of investigation. Methods: We analysed the expression and function of RARRES1 with The Cancer Genome Atlas (TCGA) database. The Kaplan-Meier curve was adopted to estimate survival. RARRES1-correlated genes were obtained from the UALCAN database and subjected to Gene Ontology (GO) enrichment and protein-protein interaction (PPI) network analyses. The correlation analysis between tumor-infiltrating immune cells and selected genes were performed with TIMER database. We also investigated the possible function of RARRES1 in KIRC by coculturing Caki-1 cells with THP-1 cells. Immunofluorescence assay was performed to study the RARRES1 expression in difference grade KIRC tissues. Results: The expression of RARRES1 was negatively correlated with survival in KIRC patients. The GO biological process term most significantly enriched with the RARRES1-correlated genes was regulation of cell adhesion. ICAM1, which exhibited a relatively highest correlation with RARRES1, is positively correlated with the infiltration level of macrophages. RARRES1 could enhance the expression of ICAM1 in Caki-1 cells and then induce the activation of M1 THP-1 cells to decrease the viability and induce the apoptosis of Caki-1 cells. Conclusion: RARRES1 plays an antitumor role by promoting ICAM1 expression and inducing the activation of M1 macrophages. We offer insights into the molecular mechanism of KIRC and reveal a potential therapeutic target.

Microwave ablation with local pleural anesthesia for subpleural pulmonary nodules: our experience.

Objectives: To explore the efficacy and safety of local pleural anesthesia (LPA) for relieving pain during microwave ablation (MWA) of pulmonary nodules in the subpleural regions. Materials and Methods: From June 2019 to December 2021, 88 patients with 97 subpleural nodules underwent percutaneous CT-guided MWA. Patients were divided into two groups according to whether LPA was applied; 53 patients with local pleural anesthesia during MWA; and 35 patients with MWA without LPA. The differences in technical success, pre-and post- and intra-operative visual analog scale (VAS) pain scores, complications of the procedure, and local progression-free survival (LPFS) between the two groups were assessed. Thus, to evaluate the efficacy and safety of MWA combined with LPA for treating subpleural nodules. Results: In this study, the procedures in all patients of both groups achieved technical success according to pre-operative planning. There was no statistically significant difference in the pre-operative VAS pain scores between the two groups. Intra-operative VAS scores were significantly higher in the non-LPA (NLPA) group than in the LPA group. They remained significantly higher in the NLPA group than in the LPA group during the short postoperative period. Analgesics were used more in the NLPA group than in the LPA group intra- and postoperatively, with a statistically significant difference, especially during the MWA procedures. The overall LPFS rates were 100%, 98.333%, 98.333%, and 98.333% at 1, 3, 6, and 12 months postoperatively in the LPA group and 100%, 97.297%, 94.595%, and 94.595% postoperatively in the NLPA group, respectively. Tumor recurrence occurred in one and two patients with lung adenocarcinoma in the LPA and NLPA groups. The incidence of pneumothorax was significantly higher in the NLPA group (25,714%, 9/35) than in the LPA group (15.094%, 8/53), and there were three cases of pleural effusion (blood collection) and one case of pulmonary hemorrhage in the NLPA group. Conclusion: Percutaneous CT-guided MWA is a safe and effective treatment for subpleural pulmonary nodules. Applying a combined LPA technique can reduce the patient's pain and complications during and after the MWA. The long-term efficacy must be verified in more patients and a longer follow-up.

Study of epirubicin sustained-release chemoablation in tumor suppression and tumor microenvironment remodeling.

Introduction: Although intratumoral chemoablation can obtain an impressive therapeutic effect, there is still incomplete ablation and tumor recurrence in some patients. This could be due to the short retention time of the drug in the tumor, the limited distribution of intratumoral drugs, and, beyond that, the immunotolerance caused by the tumor microenvironment (TME). There is still an urgent need to find an optimal drug sustained-release carrier and figure out the impact of regional injection to TME. Methods: In this study, we supposed to use polyethylene glycol (PEG) hydrogel as a drug carrier to improve the retention time of the drug to extend the exposure of tumor cells and investigate the feasibility of combination local Epirubicin injection with anti-PD-L1. Results: The results revealed obvious tumor suppression based on the tumor volume and the inhibition time of tumor growth in the A549 lung cancer mouse model after local injection. Furthermore, the enhanced antitumor effects of the combination of systematic anti- programmed death ligand 1 (PD-L1) therapy with local chemoablation (EPI-GEL/PD-L1) for abscopal tumor reduction in the 4T1 breast model were also observed. Flow cytometry analysis of the tumor and blood samples showed significant variations in the proportions of PD-L1+ and CD3+CD8+PD-1+ cells before and after anti-PD-L1 therapy. On day 4 after local injection of the EPI gel, the expression of PD-L1 in abscopal tumors was upregulated, while the expression of PD-L1 in bilateral tumors in mice was significantly reduced after anti-PD-L1 treatment. The proportion of CD3+CD8+PD-1+ cells in the tumor and circulating blood in the EPI-GEL/PD-L1 group was decreased compared with that in the EPI-GEL (single injection of epirubicin) group. Discussion: The combination of local injection of the chemoablation agent with anti-PD-L1 monoclonal antibody (mAb) therapy may strengthen the antitumor activity, and the use of PEG hydrogel as the drug carrier can extend the retention time of the chemoablation agent around the tumor, maintaining a long-term tumor-killing activity.

A preliminary comparative study of percutaneous CT-guided cryoablation with surgical resection for osteoid osteoma.

BACKGROUND: The traditional treatment for osteoid osteoma is the nidus' surgical resection, which was difficult to eradicate with more invasive and complications because of osteosclerosis surrounding the nidus. This study aimed to analyze the efficacy and safety of percutaneous CT-guided cryoablation of osteoid osteoma at different sites (especially refractory sites such as the spine). METHODS: Fifteen patients with osteoid osteoma who underwent cryoablation at our institution were analyzed retrospectively on their imaging data and clinical visual analog scale (VAS) pain scores before and after the procedure. Fifty-three patients underwent surgical resection during the period were also included in this study as a control group. Treatment efficacy was assessed primarily by comparing the differences in VAS scores at different time points in each group of patients by paired-sample t-test. Differences in length of hospital stay and complications between the two groups were also compared. RESULTS: The technical success rate was 100% in both the cryoablation and surgical resection group. Cryoablation had a significantly shorter hospitalization time than surgery (p = 0.001). Clinically, the post-operative VAS scores were all significantly improved compared to the pre-operative period, and the clinical cure was achieved in both groups. Surgical operations had more complications than cryoablation, although there was no significant difference. In the group of cryoablation, only one patient had mild numbness of the left lower extremity, which relieved itself; two patients had mild post-operative pain. No patients in the cryoablation group experienced recurrence during the follow-up period. In the surgery group, three of the patients experienced massive bleeding (>500 ml), and two underwent transfusion therapy. Only one patient in the surgical resection group experienced a recurrence at 29 months postoperatively and underwent a second resection. All patients had local scars on the skin after surgical resection. CONCLUSION: Cryoablation is a minimally invasive, safe, and effective treatment strategy for osteoid osteoma, and is fully comparable to surgical resection.

CCR4, CCR8, and P2RY14 as Prognostic Factors in Head and Neck Squamous Cell Carcinoma Are Involved in the Remodeling of the Tumor Microenvironment.

The tumor microenvironment (TME) plays a critical role in the initiation and progression of cancer. However, the specific mechanism of its regulation in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we first applied the ESTIMATE method to calculate the immune and stromal scores in patients' tumor tissues from The Cancer Genome Atlas (TCGA) database. GSE41613, GSE30784, and GSE37991 data sets from the Gene Expression Omnibus (GEO) database were recruited for further validation. Differentially expressed genes (DEGs) were identified and then analyzed by Cox regression analysis and protein-protein interaction (PPI) network construction. DEGs significantly associated with prognosis and TME will be identified as hub genes. These genes were also validated at the protein level by immunohistochemical analysis of 10 pairs of primary tumor tissues and the adjacent normal tissues from our institution. The relationship between hub genes expression and immune cell fraction estimated by CIBERSORT software was also examined. 275 DEGs were significantly associated with TME. CCR4, CCR8, and P2RY14 have then identified as hub genes by intersection Cox and PPI analysis. Further investigation revealed that the expression of CCR4, CCR8, and P2RY14 was negatively correlated with clinicopathological characteristics (clinical stage, T stage) and positively associated with survival in HNSCC patients, especially in male patients. The expression of CCR8 and P2RY14 was lower in males than in females. CCR8 and P2RY14 were differentially expressed in tumor tissues than normal tissues, and the results were validated at the protein level by immunohistochemistry experiments. Gene set enrichment analysis (GSEA) showed that the high expression groups' hub genes were mainly enriched for immune-related activities. In the low-expression groups, genes were primarily enriched in metabolic pathways. CIBERSORT results showed that the expression of these genes was all negatively correlated with the fraction of memory B cells and positively correlated with the fraction of the other four cells, including naive B cells, resting T cells CD4 memory, T cells follicular helper, and T cells regulatory (Tregs). The results suggest that CCR4, CCR8, and P2RY14 may be responsible for maintaining the immune dominance of TME, thus leading to a better prognosis.

Establishment of a modified percutaneous CT-guided paraspinal intramuscular VX-2 squamous cell carcinoma dual tumor model in rabbits.

BACKGROUND: The rabbit VX-2 tumor model is a commonly used transplanted tumor model and is widely used in surgical, radiological, and interventional studies. Most of the known tumor models for each site are single solid tumors. This study aimed to establish an accurate and stable intramuscular dual tumor model guided by computed tomography (CT). METHODS: In this study, we compared three different inoculation methods to select the most appropriate dual tumor model. Six New Zealand White rabbits were used as tumor-carrying rabbits for tumor harvesting. Thirty rabbits were divided into three groups as experimental rabbits. Group A applied the tumor cell suspension method, in which the suspension was injected into the designated location with a syringe under CT guidance. Groups B and C used tumor tissue strips obtained in vivo or under direct in vitro vision. The tumor tissue strips were implanted into the designated locations using a guide needle under CT guidance. The differences in tumorigenic rate, the size difference between bilateral tumors, and metastasis between the three methods were compared. RESULTS: It was found that group A obtained a 100% tumor survival rate, but the size of the tumor was more variable, and needle tract implantation metastasis occurred in 5 cases. In group B, tumor tissue strips were taken in vivo for implantation, in which one case failed to survive. Tumor tissue strips in group C were obtained in vitro under direct vision. The tumor tissue strips obtained in vitro by puncture using a biopsy needle in group C had a 100% tumorigenicity rate and stable tumor size. No significant needle tract implantation metastases were found in either group B or C. The variance of tumor size obtained in group A was significantly higher than in groups B and C. The variance of tumor size in group C was the smallest. Group C had high tumorigenicity and a more stable size and morphology of the formed tumors. CONCLUSION: The results showed that the method of obtaining tumor tissue strips using in vitro direct vision puncture and implanting them into the muscle with CT guidance and guide needles can establish an accurate and stable dual tumor model. This dual tumor model can provide substantial support for relevant preclinical studies.

Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver: follow-up of DCE-MRI and pathological observations.

BACKGROUND: High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo. METHODS: Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables. RESULTS: Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ±â€Š0.02 vs. 0.08 ±â€Š0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ±â€Š0.88 cm2vs. 3.20 ±â€Š0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ±â€Š0.83 cm2vs. 1.30 ±â€Š0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ±â€Š0.02 vs. 0.73 ±â€Š0.06 vs. 0.68 ±â€Š0.07, F = 241.300, P < 0.001) and heat shock protein 70 (HSP70) (0.03 ±â€Š0.01 vs. 0.46 ±â€Š0.09 vs. and 0.42 ±â€Š0.07, F = 64.490, P < 0.001) were significantly different between the untreated, IRE and H-FIRE zones, but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone (both P > 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ±â€Š3.77°C vs. 16.20 ±â€Š7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone. CONCLUSIONS: H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Predicting the Clinical Outcome of Lung Adenocarcinoma Using a Novel Gene Pair Signature Related to RNA-Binding Protein.

Adenocarcinoma is the most common type of lung cancer, and patients have varying prognoses. RNA-binding proteins (RBP) are deemed to be closely associated with tumorigenesis and development, but the exact mechanism is currently unknown. This study was aimed at constructing a new robust prognostic model based on RNA-binding protein-related gene pair scores for better clinical guidance. The model for this study was constructed based on data of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Prognosis-related RBP gene pair models were created based on differentially expressed genes, and the accuracy of the models was verified in a different age, staging, and other subdatasets. A total of 379 RNA-binding protein-related genes were differentially expressed in tumor tissue. From these genes, we constructed a prognostic model consisting of 33 gene pairs, which were found to be significantly associated with survival in TCGA dataset (P < 0.0001, hazard ratio (HR) = 4.380 (3.139 to 6.111)) and different subdatasets. As expected, the results were verified in the GEO validation cohort (P = 7.8 × 10-3, HR = 1.597 (1.095 to 2.325)). We found that the signature exhibited an independent prognostic factor in both the univariate and multivariate Cox regression analyses (P < 0.001). CIBERSORT was applied to estimate the fractions of infiltrated immune cells in bulk tumor tissues. CD8 T cells, activated dendritic cells, regulatory T cells (Tregs), and activated CD4 memory T cells presented a significantly lower fraction in the high-risk group (P < 0.01). Patients in the high-risk group had significantly higher tumor mutational burden (TMB) (P = 4.953e - 04) and lower levels of immune cells (P = 3.473e - 05) and stromal cells (P = 0.005) in the tumor microenvironment than those in the low-risk group. Furthermore, the Protein-protein interaction (PPI) network and various enrichment analyses have genuinely uncovered the interrelationships and potential functions of the RBP genes within the model. The results of the present study validated the importance of RNA-binding proteins in tumorigenesis and progression and support the RBP gene-related signature as a promising marker for prognosis prediction in lung adenocarcinoma.