Combination of percutaneous thermal ablation and adoptive Th9 cell transfer therapy against non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the predominant malignancies globally. Percutaneous thermal ablation (PTA) has gained widespread use among NSCLC patients, with the potential to elicit immune responses but limited therapeutic efficacies for advanced-stage disease. T-helper type 9 (Th9) cells are a subset of CD4+ effector T cells with robust and persistent anti-tumor effects. This study proposes to develop PTA-Th9 cell integrated therapy as a potential strategy for NSCLC treatment. METHODS: The therapeutic efficacies were measured in mice models with subcutaneously transplanted, recurrence, or lung metastatic tumors. The tumor microenvironments (TMEs) were evaluated by flow cytometry. The cytokine levels were assessed by ELISA. The signaling molecules were determined by quantitative PCR and Western blotting. The translational potential was tested in the humanized NSCLC patient-derived xenograft (PDX) model. RESULTS: We find that PTA combined with adoptive Th9 cell transfer therapy substantially suppresses tumor growth, recurrence, and lung metastasis, ultimately extending the survival of mice with NSCLC grafts, outperforming both PTA and Th9 cell transfer monotherapy. Analysis of TMEs indicates that combinatorial therapy significantly augments tumor-infiltrating Th9 cells, boosts anti-tumor effects of CD8+ T cells, and remodels tumor immunosuppressive microenvironments. Moreover, combinatorial therapy significantly strengthens the regional and circulation immune response of CD8+ T cells in mice with tumor lung metastasis and induces peripheral CD8+ T effector memory cells in mice with tumor recurrence. Mechanically, PTA reinforces the anti-tumor ability of Th9 cells primarily through upregulating interleukin (IL)-1ß and subsequently activating the downstream STAT1/IRF1 pathway, which could be effectively blocked by intercepting IL-1ß signaling. Finally, the enhanced therapeutic effect of combinatorial therapy is validated in humanized NSCLC PDX models. CONCLUSIONS: Collectively, this study demonstrates that combinatorial therapy displays robust and durable anti-tumor efficacy and excellent translational potential, offering excellent prospects for translation and emerging as a promising approach for NSCLC treatment.

Study of vision-related resting-state activity in suprasellar tumor patients with postoperative visual damage.

INTRODUCTION: The objective of this study was to investigate changes in vision-related resting-state activity in patients with suprasellar tumors (ST) who experienced vision deterioration after surgery. METHODS: Twelve patients with ST and vision deterioration after surgery were included in the study. Resting-state functional connectivity (FC) was compared before and after surgery using a seed-based analysis with a priori specified regions of interest (ROIs) within the visual areas. The differences between the two groups were identified using a paired t-test. RESULTS: The data showed a decrease in FC within and between the dorsal and ventral pathways, as well as in the third pathway in ST patients. The middle temporal visual cortex (MT+) showed a decreased FC with more regions than other visual ROIs. The data also revealed an increase in FC between the visual ROIs and higher-order cortex. The superior frontal gyrus/BA8 showed an increased FC with more ROIs than other high-order regions, and the hOC4d was involved in an increased FC with more high-order regions than other ROIs. CONCLUSIONS: The study results indicate significant neural reorganization in the vision-related cortex of ST patients with postoperative vision damage. Most subareas within the visual cortex showed remarkable neural dysfunction, and some highe-order cortex may be primarily involved in top-down control of the subareas within the visual cortex. The hot zones may arise in the processing of "top-down" influence.

DNA-PK-Mediated Cytoplasmic DNA Sensing Stimulates Glycolysis to Promote Lung Squamous Cell Carcinoma Malignancy and Chemoresistance.

Detection of cytoplasmic DNA is an essential biological mechanism that elicits IFN-dependent and immune-related responses. A better understanding of the mechanisms regulating cytoplasmic DNA sensing in tumor cells could help identify immunotherapeutic strategies to improve cancer treatment. Here we identified abundant cytoplasmic DNA accumulated in lung squamous cell carcinoma (LUSC) cells. DNA-PK, but not cGAS, functioned as a specific cytoplasmic DNA sensor to activate downstream ZAK/AKT/mTOR signaling, thereby enhancing the viability, motility, and chemoresistance of LUSC cells. DNA-PK-mediated cytoplasmic DNA sensing boosted glycolysis in LUSC cells, and blocking glycolysis abolished the tumor-promoting activity of cytoplasmic DNA. Elevated DNA-PK-mediated cytoplasmic DNA sensing was positively correlated with poor prognosis of human patients with LUSC. Targeting signaling activated by cytoplasmic DNA sensing with the ZAK inhibitor iZAK2 alone or in combination with STING agonist or anti-PD-1 antibody suppressed the tumor growth and improved the survival of mouse lung cancer models and human LUSC patient-derived xenografts model. Overall, these findings established DNA-PK-mediated cytoplasmic DNA sensing as a mechanism that supports LUSC malignancy and highlight the potential of targeting this pathway for treating LUSC. SIGNIFICANCE: DNA-PK is a cytoplasmic DNA sensor that activates ZAK/AKT/mTOR signaling and boosts glycolysis to enhance malignancy and chemoresistance of lung squamous cell carcinoma.

Cerebellar gray matter alterations predict deep brain stimulation outcomes in Meige syndrome.

BACKGROUND: The physiopathologic mechanism of Meige syndrome (MS) has not been clarified, and neuroimaging studies centering on cerebellar changes in MS are scarce. Moreover, even though deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been recognized as an effective surgical treatment for MS, there has been no reliable biomarker to predict its efficacy. OBJECTIVE: To characterize the volumetric alterations of gray matter (GM) in the cerebellum in MS and to identify GM measurements related to a good STN-DBS outcome. METHODS: We used voxel-based morphometry and lobule-based morphometry to compare the regional and lobular GM differences in the cerebellum between 47 MS patients and 52 normal human controls (HCs), as well as between 31 DBS responders and 10 DBS non-responders. Both volumetric analyses were achieved using the Spatially Unbiased Infratentorial Toolbox (SUIT). Further, we performed partial correlation analyses to probe the relationship between the cerebellar GM changes and clinical scores. Finally, we plotted the receiver operating characteristic (ROC) curve to select biomarkers for MS diagnosis and DBS outcomes prediction. RESULTS: Compared to HCs, MS patients had GM atrophy in lobule Crus I, lobule VI, lobule VIIb, lobule VIIIa, and lobule VIIIb. Compared to DBS responders, DBS non-responders had lower GM volume in the left lobule VIIIb. Moreover, partial correlation analyses revealed a positive relationship between the GM volume of the significant regions/lobules and the symptom improvement rate after DBS surgery. ROC analyses demonstrated that the GM volume of the significant cluster in the left lobule VIIIb could not only distinguish MS patients from HCs but also predict the outcomes of STN-DBS surgery with high accuracy. CONCLUSION: MS patients display bilateral GM shrinkage in the cerebellum relative to HCs. Regional GM volume of the left lobule VIIIb can be a reliable biomarker for MS diagnosis and DBS outcomes prediction.

Relative vaccine effectiveness against Delta and Omicron COVID-19 after homologous inactivated vaccine boosting: a retrospective cohort study.

ObjectiveTwo COVID-19 outbreaks occurred in Henan province in early 2022-one was a Delta variant outbreak and the other was an Omicron variant outbreak. COVID-19 vaccines used at the time of the outbreak were inactivated, 91.8%; protein subunit, 7.5%; and adenovirus5-vectored, 0.7% vaccines. The outbreaks provided an opportunity to evaluate variant-specific breakthrough infection rates and relative protective effectiveness of homologous inactivated COVID-19 vaccine booster doses against symptomatic infection and pneumonia. DESIGN: Retrospective cohort study METHODS: We evaluated relative vaccine effectiveness (rVE) with a retrospective cohort study of close contacts of infected individuals using a time-dependent Cox regression model. Demographic and epidemiologic data were obtained from the local Centers for Disease Control and Prevention; clinical and laboratory data were obtained from COVID-19-designated hospitals. Vaccination histories were obtained from the national COVID-19 vaccination dataset. All data were linked by national identification number. RESULTS: Among 784 SARS-CoV-2 infections, 379 (48.3%) were caused by Delta and 405 (51.7%) were caused by Omicron, with breakthrough rates of 9.9% and 17.8%, respectively. Breakthrough rates among boosted individuals were 8.1% and 4.9%. Compared with subjects who received primary vaccination series ≥180 days before infection, Cox regression modelling showed that homologous inactivated booster vaccination was statistically significantly associated with protection from symptomatic infection caused by Omicron (rVE 59%; 95% CI 13% to 80%) and pneumonia caused by Delta (rVE 62%; 95% CI 34% to 77%) and Omicron (rVE 87%; 95% CI 3% to 98%). CONCLUSIONS: COVID-19 vaccination in China provided good protection against symptomatic COVID-19 and COVID-19 pneumonia caused by Delta and Omicron variants. Protection declined 6 months after primary series vaccination but was restored by homologous inactivated booster doses given 6 months after the primary series.

Application of thermal alkaline hydrolysis technology to improve the loading and in-vitro release of gallic acid in UiO-66.

The purpose of this study was to treat UiO-66 (University of Oslo 66) under suitable thermal alkaline hydrolysis condition to realize the loading of gallic acid. UiO-66-SH (UiO-66-separated-heating) was obtained by separated heating UiO-66 and 0.2 M KOH aqueous solution to 120 ℃ before mixing for 3 h. The material was in an amorphous state, maintained the octahedron structure and size of UiO-66. UiO-66-SH has better porosity and specific surface area than UiO-66, and had good thermal stability until heated to 1000 ℃. Furthermore, UiO-66-SH had very little influence of the cellular activity of human normal heptical cell line, demonstrating its good biocompatibility. The prepared UiO-66-SH could successfully adsorb gallic acid and control the release of gallic acid in simulated gastric fluid (∼58% vs. âˆ¼ 88% of free gallic acid). This study will be conducive to preparation of appropriate carrier used to load with polyphenolic compounds such as gallic acid.

Pro-inflammatory and proliferative microglia drive progression of glioblastoma.

Scant understanding of the glioblastoma microenvironment and molecular bases hampers development of efficient treatment strategies. Analyses of gene signatures of human gliomas demonstrate that the SETD2 mutation is correlated with poor prognosis of IDH1/2 wild-type (IDH-WT) adult glioblastoma patients. To better understand the crosstalk between SETD2 mutant (SETD2-mut) glioblastoma cells and the tumor microenvironment, we leverage single-cell transcriptomics to comprehensively map cellular populations in glioblastoma. In this study, we identify a specific subtype of high-grade glioma-associated microglia (HGG-AM). Further analysis shows that transforming growth factor (TGF)-ß1 derived from SETD2-mut/IDH-WT tumor cells activates HGG-AM, exhibiting pro-inflammation and proliferation signatures. Particularly, HGG-AM secretes interleukin (IL)-1ß via the apolipoprotein E (ApoE)-mediated NLRP1 inflammasome, thereby promoting tumor progression. HGG-AM present extensive proliferation and infiltration to supplement the activated microglia pool. Notably, TGF-ß1/TßRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.

Down-regulation of miR-340-5p promoted osteogenic differentiation through regulation of runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells.

Diabetic osteoporosis (DOP) is a chronic complication of diabetes in the skeletal system. High level of miR-340-5p may be harmful to the bone formation. In this study, the DOP model of rats was successfully established via streptozotocin (STZ) and ovariectomy (OVX) treatment. It was manifested by reduced body weight, insulin level, alkaline phosphatase (ALP) activity, and osteocalcin (OCN) and collagen-I expressions, as well as increased concentration of fasting blood glucose. Moreover, we found that miR-340-5p expression was increased while runt-related transcription factor-2 (RUNX2) was decreased in femurs. Furthermore, the effects of miR-340-5p on osteogenic differentiation (OD) in high glucose (HG)-treated MC3T3-E1 cells were explored. Exposure to OD and HG contributed to elevated miR-340-5p level. Inhibition of miR-340-5p enhanced ALP level, calcium deposition, and OCN, collagen-I and RUNX2 levels. On the contrary, miR-340-5p overexpression reversed these promotional effects. Luciferase assay indicated that RUNX2 may be a target gene of miR-340-5p. Moreover, RUNX2 deficiency decreased miR-340-5p inhibition-induced ALP activity, calcium accumulation and OCN, collagen-I, RUNX2 levels. In short, the above findings revealed that inhibition of miR-340-5p facilitated osteogenic differentiation through regulating RUNX2 in MC3TC-E1 cells, which provided targeted therapeutic strategies for the treatment of DOP.

Treatment of Residual, Recurrent, or Metastatic Intracranial Hemangiopericytomas With Stereotactic Radiotherapy Using CyberKnife.

PURPOSE: Hemangiopericytomas are aggressive tumors known for their recurrence. The purpose of this study was to evaluate the management of residual, recurrent, and metastatic intracranial hemangiopericytomas using CyberKnife (CK) stereotactic radiotherapy (SRT). MATERIALS AND METHODS: Data were collected from 15 patients (28 tumors; eight men and seven women; 32-58 years) with residual, recurrent, or metastatic intracranial hemangiopericytomas, who were treated with stereotactic radiotherapy using CyberKnife between January 2014 and August 2019. All patients had previously been treated with surgical resection. Initial tumor volumes ranged from 0.84 to 67.2 cm3, with a mean volume of 13.06 cm3. The mean marginal and maximum radiosurgical doses to the tumors were 21.1 and 28.76 Gy, respectively. The mean follow-up time for tumors was 34.5 months, ranging from 13 to 77 months. RESULTS: 15 patients were alive after treatment; the mean post-diagnosis survival at censoring was 45.6 months (range 13-77 months). The volumes of the 28 tumors in the 15 followed patients were calculated after treatment. Postoperative magnetic resonance imaging revealed a mean tumor volume of 6.72 cm3 and a range of 0-67.2 cm3, with the volumes being significantly lower than pretreatment values. Follow-up imaging studies demonstrated tumor disappearance in seven (25%) of 28 tumors, reduction in 14 (50%), stability in one (3.57%), and recurrence in six (21.4%). Total tumor control was achieved in 22 (78.5%) of 28 tumors. The tumor grade and fraction time were not significantly associated with progression-free survival. Intracranial metastasis occurred in three patients, and extraneural metastasis in one patient. CONCLUSIONS: On the basis of the current results, stereotactic radiotherapy using CyberKnife is an effective and safe option for residual, recurrent, and metastatic intracranial hemangiopericytomas. Long-term close clinical and imaging follow-up is also necessary.

A nationwide post-marketing survey of knowledge, attitudes and recommendations towards human papillomavirus vaccines among healthcare providers in China.

Since licensure of human papillomavirus (HPV) vaccine in mainland China, little research has been conducted about healthcare providers' (HCPs) understanding and recommendation of HPV vaccine. A multi-stage convenience sample of Chinese HCPs (N = 5270) were surveyed, involving obstetrician-gynecologists, HCPs from Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC) and other non-HPV closely related professions. Binary logistic regression was conducted to explore factors associated with knowledge and recommendation behaviors. Overall, HCPs showed basic HPV/HPV vaccine knowledge with median (interquartile range) score at 9.5 (7.5-11.6) out of 16 and relatively high recommendation behavior (74.8%). Identified knowledge gaps among HCPs included risk factors of HPV infection, best time to vaccinate, prophylactic functions of HPV vaccine and especially classification of low-risk and high-risk types. Profession-specific analysis in individual knowledge item showed HCPs from CHC were suboptimal on HPV while obstetrician-gynecologists were less competent on HPV vaccine knowledge. Obstetrician-gynecologists also recommended vaccination less frequently than HCPs from DEPI and CHC. Besides being key predictors of recommendation practice (2.74, 95% CI: 2.34-3.21), knowledge shared independent determinants with recommendation behavior on age and ethnicity and additionally associated with education and title by itself. Findings highlight overall and profession-specific gaps on HPV and HPV vaccine knowledge and recommendation practice. Future education and training efforts should be profession-niche-targeting and focus much on HCPs with lower title or education background and from minorities.

A nationwide post-marketing survey of knowledge, attitude and practice toward human papillomavirus vaccine in general population: Implications for vaccine roll-out in mainland China.

BACKGROUND: Human papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China. METHODS: Participants aged 18-45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics. RESULTS: 4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines. CONCLUSIONS: Findings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.

Safety and effectiveness of multi-antenna microwave ablation-oriented combined therapy for large hepatocellular carcinoma.

BACKGROUND: In patients with a large, unresectable hepatocellular carcinoma (HCC), the primary recommendation is for transarterial chemoembolization (TACE) but used alone TACE is not typically curative. Combinations of TACE followed in a delayed fashion by single-applicator thermal ablation have also been suboptimal. As an alternative, we investigated the combination of TACE followed within 1-3 days by multi-antenna microwave ablation (MWA) in patients with a large HCC, to determine the feasibility, safety, local control, and short-term survival rates of this approach. METHODS: We retrospectively studied 43 patients with a large HCC (mean diameter, 8.8 cm; SD, 2.8 cm) treated between July 2015 and July 2018, who underwent TACE followed within 3 days by multi-antenna simultaneous MWA. We measured the liver and renal function before and after treatment, recorded complications, used three-dimensional software and imaging to calculate tumor necrosis rates at 1 month after therapy, and calculated overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. RESULTS: Mean follow up was 12.2 (range, 3.5-35.6) months. All patients completed the treatment protocol. At 1 month after combined therapy, tumor necrosis was complete in 16 (37.2%), nearly complete in 19 (44.2%), and partial in 8 (18.6%) patients. The 1- and 2-year OS rates were 64.0% and 46.8%, respectively, with a median OS of 23.0 months; and the 1- and 2-year PFS rates were 19.9% and 4.4%, respectively, with a median PFS of 4.2 months. A transient change in liver function occurred 3 days after MWA but resolved within 1 month. Only two patients had major complications, which were treatable and resolved. CONCLUSION: Multi-antenna MWA-oriented combined therapy is feasible and well tolerated, and it results in satisfactory initial local control and short-term survival in some but not all patients with a large HCC.

Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer via DNA damage.

Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] (D0402) on Kunming(KM) mice bearing tumor (H22 hepatic cancer) has been evaluated, and the results showed that the tumor weight of mice treated with 0.22 mg/(kg·day) D0402 via i.v. administration for 7 days decreased about 31.79% compared to the control group, while the body weight, as well as the thymus, spleen, liver, lung, and kidney indices of mice treated with D0402 observed almost no loss compared to the control group. Furthermore, the mechanism studies on anti-angiogenic showed that D0402 could inhibit the formation of angiogenesis in the transgenic Tg(fli1a: EGFP) zebrafish. After treated with D0402, the sub-intestinal vessels(SIVs) of the zebrafish became disordered and chaotic, and was dosage dependent. Moreover, the TUNEL analysis and comet assays revealed that D0402 can induce apoptosis of HepG2 cell through DNA damage, and this was further demonstrated by immunofluorescence analysis with the number of γ-H2AX increased following the increasing amount of D0402. Besides, in vivo toxicity of D0402 has also been investigated on the development of zebrafish embryo, and the results showed that there were no death or development delay occurred for zebrafish embryo treated with D0402 up to concentration of 60 µM. All in together, this study suggested that D0402 can be developed as a potential inhibitor against liver cancer through co-junction of anti-angiogenesis and apoptosis-inducing via DNA damage in the near future.

Microsurgical treatment of craniopharyngioma: Experiences on 183 consecutive patients.

This study aimed to summarize the clinical experiences and postoperative effects of microsurgical approaches for craniopharyngioma.A total of 183 craniopharyngioma patients who underwent microsurgical treatment since March 2009 to March 2015 in our hospital were included in current research. Surgical approaches were selected based on preoperative evaluations, including tumor locations, sizes, and growth patterns. Active measurements to manage water-electrolyte disorder and insipidus were taken for postoperative treatments. During the follow-up, patients were monitored for residual or recurrent tumor by postoperative contrast MRI scans done 1 to 3 months after surgery.The used surgical approaches were as follows: frontopterional approach (76 cases), anterior interhemispheric approach (58 cases), transcallosal approach (10 cases), transsphenoidal approach (15 cases), unilateral subfrontal approach (15 cases), and combined approaches (9 cases). Around 124 cases (72.7%) received total tumor resection, 37 patients (20.2%) underwent subtotal resection, and 13 patients (7.1%) underwent partial removal. No significant difference was found on the postoperative complications among the different microsurgical approaches (all, P > .05). A total of 111 cases had an intact pituitary stalk preservation and 26 cases had partially preserved stalks during surgery. Visual improvement was achieved in 54 patients and visual deterioration occurred in 22 cases. Postoperative insipidus appeared in 114 cases and water-electrolyte disorder occurred in 99 cases. The postsurgical follow-up ranged from 3 to 69 months with a mean duration of 27.3 months and 23 patients suffered recurrence.Based on careful preoperative evaluation, microsurgical treatments may be safe and effective approach to improve postoperative outcomes of craniopharyngioma patients.

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers.

PURPOSE: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume. MATERIALS AND METHODS: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15 minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20 mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation. RESULTS: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p < .001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p < .001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p < .001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p < .001). CONCLUSION: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.

Diffusion Tensor Imaging of Axonal and Myelin Changes in Classical Trigeminal Neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is commonly associated with pathologic factors of axonopathy and demyelination resulting from neurovascular compression at the trigeminal root entry zone (REZ). Decompression surgery can relieve TN pain, likely by resolving such structural abnormalities. To test this hypothesis, we used diffusion tensor imaging (DTI) to capture the full extent of trigeminal microarchitecture changes in vivo in patients with TN. METHODS: Twenty-four patients with TN were compared with 28 controls. DTI metrics of fractional anisotropy (FA) and mean, parallel, and perpendicular diffusivities (MD, λ||, and λ⊥, respectively) were calculated in isolation at each trigeminal REZ. In 6 patients with pain relief following decompression surgery, repeated studies were performed 2 times (1 week and 4-6 months) after surgery to detect dynamic changes in FA, MD, λ||, and λ⊥. RESULTS: We observed significant FA reductions and increased diffusivity at the affected trigeminal REZ, corresponding to known underlying pathologic changes, including axonal edema and demyelination. Specifically, our results showed that these DTI-derived metrics are discriminating features for patients with TN according to the support vector machine approach. After effective treatment, diffusion recovery at 1 week was mainly due to the decrease in λ|| (consistent with axonal membrane stabilization), whereas at 4-6 months it was due to the predominant reduction in λ⊥ (consistent with remyelination). CONCLUSIONS: Together, these results support that DTI permits the noninvasive detection of the trigeminal microstructural abnormalities underlying TN in vivo, and DTI-derived metrics could be considered surrogate markers of the axonal and myelin states for monitoring patients.

Altered functional networks in long-term unilateral hearing loss: A connectome analysis.

Introduction: In neuroimaging studies, long-term unilateral hearing loss (UHL) is associated with functional changes in specific brain regions and connections; however, little is known regarding alterations in the topological organization of whole-brain functional networks and whether these alterations are related to hearing behavior in UHL patients. Methods: We acquired resting-state fMRI data from 21 patients with UHL caused by acoustic neuromas and 21 matched healthy controls. Whole-brain functional networks were constructed by measuring interregional temporal correlations of 278 brain regions. Alterations in interregional functional connectivity and topological properties (e.g., small-world, efficiency, and nodal centrality) were identified using graph-theory analysis. The subjects also completed a battery of hearing behavior measures. Results: Both UHL patients and controls exhibited efficient small-world properties in their functional networks. Compared with controls, UHL patients showed increased and decreased nodal centrality in distributed brain regions. Furthermore, the brain regions with significantly increased and decreased functional connections associated with UHL were components of the following important networks: (1) visual network; (2) higher-order functional networks, including the default-mode and attention networks; and (3) subcortical network and cerebellum. Intriguingly, the changes in intranetwork connections in UHL were significantly correlated with disease duration and hearing level. Conclusions: This study revealed connectome-level alterations involved in multiple large-scale networks related to sensory and higher-level cognitive functions in long-term UHL patients. These reorganizations of the brain in UHL patients may depend on the stage of deafness and hearing level. Together, our findings provided empirical evidence for understanding the neuroplastic mechanisms underlying hearing impairment, establishing potential biomarkers for monitoring the progression and further treatment effects for UHL patients.

Clinicopathological analysis of myxoid proximal-type epithelioid sarcoma.

Proximal-type epithelioid sarcoma (ES) with a diffuse myxoid stroma is rare. Here, we report the case of a 33-year-old man with a perineal mass. Imaging showed the presence of a poorly demarcated 6.9 × 5.3-cm mass in the subcutaneous perineal region. Macroscopic examination showed that the resected tissues were partially necrotic. Histological examination showed that the tumor comprised numerous large or pleomorphic epithelioid cells with large vesicular nuclei and prominent nucleoli. A clear background of necrosis and inflammatory exudates was also present. Immunohistochemical examination showed that the tumor cells were positive for vimentin and CD34 - both of which were expressed throughout the cytoplasm - but typically did not express nuclear INI1 (SMARCB1). Hematoxylin-eosin staining (HE staining) showed that the mucin content of the tumor was approximately 80%. The patient was diagnosed with proximal-type ES with myxoid features. The patient died due to disease progression after 2 months of follow-up and without undergoing further treatment in our department. To our knowledge, only 2 cases of proximal-type ES with diffuse myxoid stroma have been reported. Proximal-type ES is rare, and this is the first case report of proximal ES with myxoid features in the perineal area.

miR­96 inhibits EMT by targeting AEG­1 in glioblastoma cancer cells.

The induction of epithelial to mesenchymal transition (EMT) is important for carcinogenesis and cancer progression. Previous studies have estimated that microRNA (miRNA/miR) expression is associated with EMT via the regulation of the expression of target genes. miR­96 has been reported to exhibit a correlation with the EMT process. However, the functional role of miR­96 and its mechanism in glioblastoma multiforme (GBM) remains to be completely elucidated. The objective of the present study was to investigate the functional role and mechanism of miR­96 in the migration and invasion, in addition to proliferation, apoptosis and cell cycle distribution, of GBM. In the present study, the results suggested that the introduction of miR­96 significantly inhibited the migration and invasion, in addition to proliferation and cell cycle progression, of GBM cells and promoted their apoptosis in vitro, leading to the hypothesis that miR­96 may be a potential tumor suppressor. It was subsequently confirmed that astrocyte elevated gene­1 (AEG­1) was a direct target gene of miR­96, using a luciferase assay and reverse transcription­quantitative polymerase chain reaction analysis, in addition to western blotting. miR­96 was observed to downregulate the expression of AEG­1 at the mRNA and protein levels. Notably, AEG­1 may suppress EMT by increasing the expression levels of E­cadherin, an epithelial marker, and decreasing the expression levels of vimentin, a mesenchymal marker. Therefore, it was concluded that miR­96 may impede the EMT process by downregulating AEG­1 in GBM. Additionally, it was observed that inhibition of AEG­1 led to a similar effect compared with overexpression of miR­96 in GBM. In conclusion, the results of the present study demonstrated that miR­96 may act as a tumor suppressor by regulating EMT via targeting of AEG­1, suggesting that miR­96 may be a potential biomarker and anticancer therapeutic target for GBM in the future.

Monaural-driven Functional Changes within and Beyond the Auditory Cortical Network: Evidence from Long-term Unilateral Hearing Impairment.

Long-term unilateral hearing impairment (UHI) results in changes in hearing and psychoacoustic performance that are likely related to cortical reorganization. However, the underlying functional changes in the brain are not yet fully understood. Here, we studied alterations in inter- and intra-hemispheric resting-state functional connectivity (RSFC) in 38 patients with long-term UHI caused by acoustic neuroma. Resting-state fMRI data from 17 patients with left-sided hearing impairment (LHI), 21 patients with right-sided hearing impairment (RHI) and 21 healthy controls (HCs) were collected. We applied voxel-mirrored homotopic connectivity analysis to investigate the interhemispheric interactions. To study alterations in between-network interactions, we used four cytoarchitectonically identified subregions in the auditory cortex as "seeds" for whole-brain RSFC analysis. We found that long-term imbalanced auditory input to the brain resulted in (1) enhanced interhemispheric RSFC between the contralateral and ipsilateral auditory networks and (2) differential patterns of altered RSFCs with other sensory (visual and somatomotor) and higher-order (default mode and ventral attention) networks among the four auditory cortical subregions. These altered RSFCs within and beyond the auditory network were dependent on the side of hearing impairment. The results were reproducible when the analysis was restricted to patients with severe-to-profound UHI and patients with hearing-impairment durations greater than 24 months. Together, we demonstrated that long-term UHI drove cortical functional changes within and beyond the auditory network, providing empirical evidence for the association between brain changes and hearing disorders.