The valuable role of dynamic 18F FDG PET/CT-derived kinetic parameter Ki in patients with nasopharyngeal carcinoma prior to radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Dynamic positron emission tomography/computed tomography (PET/CT) served the potential role of characterizing malignant foci. The main objective of this prospective study was to explore the advantage of dynamic PET/CT imaging in characterizing nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Patients with probable head and neck disease underwent a local dynamic PET/CT scan followed by a whole-body static scan. Patlak analysis was used to generate parametric influx rate constant (Ki) images from 48 frames obtained from a dynamic PET/CT scan. By delineating the volumes-of-interest (VOIs) of: primary tumor (PT), lymph node (LN), and normal nasopharyngeal tissues (N), we acquired the corresponding Ki mean and SUVmean of each site respectively to perform the quantitative statistical analysis. RESULTS: Qualified images of 71 patients with newly diagnosed NPC and 8 without nasopharyngeal malignant lesions were finally included. We found the correlations between Ki mean-PT and critical clinical features, including clinical stage (r = 0.368), T category (r = 0.643) and EBV-DNA copy status (r = 0.351), and Ki mean-PT differed within the group. SUVmean-PT showed correlations with clinical stage (r = 0.280) and T category (r = 0.472), but could hardly differ systematically within group of clinical features except T category. Ki mean-LN offered the positive correlations with N category (r = 0.294), M category (r = 0.238) and EBV-DNA copy status (r = 0.446), and differed within the group. In addition, Ki mean represented a sensitivity of 94.4 % and a specificity of 100 %, in distinguishing NPC from the non-NPC, when the cut-off was defined as 0.0106. When the cut-off of SUV being defined as 2.03, the sensitivity and specificity were both 100 %. CONCLUSION: Our research confirmed Ki compared favorably to SUV in characterizing NPC and found that Ki can serve as an effective imaging marker of NPC.

Reduction of phonetic mismatch negativity may depict illness course and predict functional outcomes in schizophrenia.

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes.

The efficacy of hypofractionated radiotherapy (HFRT) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: A meta-analysis.

PURPOSE: The efficacy of hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) without age restrictions remains unclear. The aim of this meta-analysis is to access the survival outcomes of HFRT in these patients. METHODS: A comprehensive electronic literature search of PubMed, Web of Science and Cochrane Library was conducted up to June 1, 2020. The main evaluation data were the overall survival (OS) rate at 12 months and 24 months and the progression-free survival (PFS) rate at 6 and 12 months. The secondary evaluation data was the incidence of radionecrosis and adverse events. The study was performed using R "meta" package. RESULTS: Eleven studies met the inclusion criteria, which totally contained 484 participants. The 12-month OS and 24-month OS rate of HFRT in GBM were 71.3% and 34.8%, while the 6-month PFS and 12-month rate were 74.0% and 40.8%. Compared to low-BED (biological equivalent dose) schedules (<78Gy), high-BED schedules may increase survival benefit both in PFS-6 (P=0.003) and PFS-12 (P=0.011), while the difference did not show on OS. Different dose per fraction had no significant effect on both OS and PFS. Incidence of radionecrosis was 14.2%. Although the overall incidence of adverse reactions cannot be quantified, the toxicity of HFRT was acceptable. CONCLUSIONS: Compared with survival data for standard treatment, HFRT seemed to improve overall survival and progression-free survival, while high BED schedules may future increase benefit on PFS. Meanwhile, the toxicity of HFRT was tolerable. Further randomised controlled clinical studies are needed to confirm these findings.

Reduced-dose bevacizumab vs. standard-dose bevacizumab in recurrent high-grade glioma: Which one is better? A meta-analysis.

BACKGROUND: Based on the effective radiological responses, bevacizumab (BEV) has been widely used in the treatment of recurrent high-grade glioma. Although the current standard dose is 5 mg/kg/week, the optimal dosage of BEV is controversial, as few dose-response studies have been performed in recent years. Therefore, we conducted a meta-analysis to explore the value of reduced-dose bevacizumab versus standard-dose bevacizumab in recurrent high-grade glioma treatment. METHODS: Three major electronic databases (PubMed, EMBASE and the Cochrane Library) were searched for eligible documents published before February 2020. Literature on low-dose bevacizumab versus conventional dose in progressive high-grade glioma was included, and the endpoints of eligible researches should be progression-free survival (PFS) and overall survival (OS). All available data were collected and then analyzed with Stata software. RESULTS: Four cohort studies were evaluated, including 552 patients (reduced-dose BEV group: 257, standard-dose BEV group: 295). Low dose BEV seems to slightly improve survival compared to conventional dose as HR < 1 indicates a protective effect, but no significant differences in OS (HR 0.77; 95 % CI 0.53-1.10; P = 0.151) and PFS (HR 0.66; 95 % CI 0.37-1.20; P = 0.175) were found between the two groups in this study. CONCLUSION: Reduced-dose bevacizumab schedule resulted in similar OS and PFS to standard-dose bevacizumab in recurrent high-grade glioma, with less side effects and less cost of treatment. Therefore, low-dose bevacizumab represents a promising therapeutic option for recurrent high-grade glioma patients. Further prospective randomized trials are needed to confirm our results.

[Vitamin E reduces radiation injury of hippocampal neurons in mice by inhibiting ferroptosis].

OBJECTIVE: To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism. METHODS: Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 µmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 µmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 µmol/L), or necroptosis inhibitor (100 µmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test. RESULTS: Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells (P < 0.05) but not in U251 cells (P > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels (P < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells (P < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance (P < 0.05), which were significantly decreased after treatment with VE (P < 0.05). CONCLUSIONS: Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.

TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma.

BACKGROUND: Thymocyte selection-associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltration, and T cells function in diverse cancers particularly lung adenocarcinoma (LUAD). METHODS: TIMER was used to analyze TOX expression in different cancers. Potential prognostic value of TOX was evaluated by the PrognoScan, Kaplan-Meier Plotter, and GEPIA2. The relationships between TOX, immune infiltration, and related gene marker sets were analyzed by TIMER and GEPIA2. Single-cell RNA-seq for T cells in LUAD was analyzed to further investigate the correlations between TOX expression and different T cells populations. RESULTS: TOX downregulates in most of the cancer types and correlates with poor prognosis in LUAD. TOX shows significant impacts on survival of LUAD with early stage, ever-smoking, or low-TMB status. Increased TOX expression positively correlates with high immune infiltration levels in most of the immune cells and functional T cells including exhausted T cells. Moreover, multiple key genes of exhausted T cells comprising PD-1, TIM-3, TIGHT, and CXCL13 have remarkable interaction with TOX. Specifically, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single-cell RNA-seq analysis for LUAD. CONCLUSION: TOX is a prognosis-related biomarker for multiple cancer types especially LUAD. Increased TOX expression significantly increase immune infiltration levels in most of the immune cells comprising CD8+ T cells, CD4+ T cells, mast cells, and functional T cells. Moreover, we verified that TOX highly correlates with exhausted T cells and is probable a critical regulator promoted T cells exhaustion in LUAD. Detection of TOX expression could help to predict prognosis and regulating TOX expression in exhausted T cells may offer a novel strategy in maximizing immunotherapy efficacy for LUAD.

Schizophrenia affects speech-induced functional connectivity of the superior temporal gyrus under cocktail-party listening conditions.

The superior temporal gyrus (STG) is involved in speech recognition against informational masking under cocktail-party-listening conditions. Compared to healthy listeners, people with schizophrenia perform worse in speech recognition under informational speech-on-speech masking conditions. It is not clear whether the schizophrenia-related vulnerability to informational masking is associated with certain changes in FC of the STG with some critical brain regions. Using sparse-sampling fMRI design, this study investigated the differences between people with schizophrenia and healthy controls in FC of the STG for target-speech listening against informational speech-on-speech masking, when a listening condition with either perceived spatial separation (PSS, with a spatial release of informational masking) or perceived spatial co-location (PSC, without the spatial release) between target speech and masking speech was introduced. The results showed that in healthy participants, but not participants with schizophrenia, the contrast of either the PSS or PSC condition against the masker-only condition induced an enhancement of functional connectivity (FC) of the STG with the left superior parietal lobule and the right precuneus. Compared to healthy participants, participants with schizophrenia showed declined FC of the STG with the bilateral precuneus, right SPL, and right supplementary motor area. Thus, FC of the STG with the parietal areas is normally involved in speech listening against informational masking under either the PSS or PSC conditions, and declined FC of the STG in people with schizophrenia with the parietal areas may be associated with the increased vulnerability to informational masking.

Face-related visual search deficits in first-episode schizophrenia.

Schizophrenia is considered a complex illness with multiple cognitive dysfunctions, including a deficit in visual processing. However, whether the deficiency of visual processing in schizophrenia is general across stimuli or stimulus-specific remains the subject of debate. In the current study, eighteen first-episode schizophrenic patients and eighteen healthy controls participated in three visual search tasks in which they were asked to search a specific target of a triangle, face identity or facial affect. The results showed that, compared to healthy controls, the accuracies for face identity and facial affect searches were significantly lower in schizophrenic patients, while the performance of the triangle search was the same. Furthermore, the accuracy of the facial affect search was negatively correlated to negative symptoms in schizophrenia. These results revealed a face-related deficit in schizophrenia and suggest that visual processing deficits in schizophrenia were stimuli-specific.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8-week, prospective, open-label, multicenter, single-arm study.

INTRODUCTION: This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. METHODS: A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. RESULTS: A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. DISCUSSION: Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.