Knockdown of SIK3 in the CA1 Region can Reduce Seizure Susceptibility in Mice by Inhibiting Decreases in GABAAR α1 Expression.

Imbalance between excitation and inhibition is an important cause of epilepsy. Salt-inducible kinase 1 (SIK1) gene mutation can cause epilepsy. In this study, we first found that the expression of SIK3 is increased after epilepsy. Furthermore, the role of SIK3 in epilepsy was explored. In cultured hippocampal neurons, we used Pterosin B, a selective SIK3 inhibitor that can inhibit epileptiform discharges induced by the convulsant drug cyclothiazide (a positive allosteric modulator of AMPA receptors, CTZ). Knockdown of SIK3 inhibited epileptiform discharges and increased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). In mice, knockdown of SIK3 reduced epilepsy susceptibility in a pentylenetetrazole (a GABAA receptor antagonist, PTZ) acute kindling experiment and increased the expression of GABAA receptor α1. In conclusion, our results suggest that blockade or knockdown of SIK3 can inhibit epileptiform discharges and that SIK3 has the potential to be a novel target for epilepsy treatment.

Free Water MR Imaging of White Matter Microstructural Changes is a Sensitive Marker of Amyloid Positivity in Alzheimer's Disease.

BACKGROUND: Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE: To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aß) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE: Retrospective. POPULATION: Thirty-eight Aß-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aß-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aß-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aß-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE: 3.0T; DTI, T1 -weighted, T2 -weighted, T2 star-weighted angiography, and Aß PET (18 F-florbetaben or 11 C-PIB). ASSESSMENT: FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS: Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS: Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION: FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

[Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats].

OBJECTIVE: To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction (POCD), neuronal apoptosis and neuron-inflammation in aged rats. METHODS: Thirty-six male SD rats aged 20 months were randomly divided into sham operation group, model group and electroacupuncture (EA) group, with 12 rats in each group. The POCD rats model was prepared by internal fixation of left tibial fracture. Five days before modeling, EA stimulation (2 Hz/15 Hz, 1 mA, 30 min) was applied to "Zusanli" (ST36), "Hegu" (LI4) and "Neiguan" (PC6) on the unaffected side of rats in the EA group, once a day for consecutive 5 d. The learning and memory abilities of rats were evaluated by water maze test 31-35 days after operation. The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining. The expressions of high mobility group protein B1 (HMGB1) and phosphorylated (p)-nuclear factor (NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining. The expression levels of interleukin (IL)-6 and IL-1ß in the hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency was prolonged (P<0.05); the frequency of crossing the original platform, ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased (P<0.05); the apoptosis rate of hippocampal neurons was significantly increased (P<0.05); the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group. Compared with the model group, the results of the above indexes were all opposite (P<0.05) in the EA group. CONCLUSION: EA preconditioning can regulate hippocampal inflammatory response, alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD, the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.

Delayed arterial symptomatic epidural hematoma on the 14th day after posterior lumbar interbody fusion: A case report.

BACKGROUND: Delayed arterial symptomatic epidural hematoma (SEH) on the 14th day after posterior lumbar interbody fusion (PLIF) is rare but it may lead to severe complications if not identified and treated in a timely manner. After diagnosis of the current case, early surgical removal of the hematoma and strict hemostasis treatment was accomplished. This case report highlights the importance of swift diagnosis and treatment in SEH patients. CASE SUMMARY: A 41-year-old male patient with a single-segment lumbar disc herniation underwent left-side PLIF. On the 14th post-operative day, the patient complained of lumbar incision pain with sudden onset accompanied by left limb radiation pain and aggravated cauda equina symptoms. Magnetic resonance imaging examination and a puncture blood draw at the incision site confirmed a delayed arterial SEH. Emergency surgical removal of the hematoma and hemostasis was performed. About 70 mL of hematoma was found in the left incision. Continuous bleeding was found in the anterior branch of the transverse process of the 4th lumbar artery in the muscle area about 2 cm below the transverse process of the 4th lumbar vertebra. A blood jet of about 10 cm in height was observed and bipolar electrocoagulation was used to stop the bleeding. Post-operative lumbar incision pain and left lower limb pain were relieved immediately and gradually disappeared. There was no recurrence during the 12-mo follow-up. CONCLUSION: For delayed arterial SEH on the 14th day after PLIF, preventive measures including pre-, intra- and post-operative prevention should be implemented.

Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.

Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated them with exposure to DNP-human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-protein expression was determined by immunoblotting. In vivo allergic responses were examined in IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) mouse models. 4-MU inhibited ß-hexosaminidase activity and histamine release dose-dependently in FcεRI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and F-actin reorganization while down-regulating IgE/Ag-induced phosphorylation of SYK, NF-κB p65, ERK1/2, p38, and JNK. Moreover, 4-MU attenuated the PCA allergic reaction (i.e., less ear thickening and dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum histamine, and IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating IgE-mediated allergic conditions.

Two new species and a new record of the genus Spininola Lszl, Ronkay amp; Witt, 2010 from China (Lepidoptera, Nolidae, Nolinae).

Two new species (Spininola yongdingensis and Spininola qianfengensis spp. nov.) are described; Spininola denticulata (Moore, 1888) is reported from China for the first time. Adults and genitalia of new species are illustrated.

FAK inhibitor PF-431396 suppresses IgE-mediated mast cell activation and allergic inflammation in mice.

Mast cells (MCs) initiate and maintain allergic inflammation. Upon being stimulated with immunoglobulin (Ig)E and antigen (Ag), MCs exhibit FcεRI (high-affinity IgE) receptor-mediated degranulation, cytokine secretion, and increased focal adhesion kinase (FAK) activity. The aims of this study were to examine mechanisms of FAK regulation in IgE-mediated MC activation and the effects of FAK inhibition on MC-mediated allergic responses. FAK activity was manipulated with short hairpin RNA (shRNA) knockdown, FAK overexpression, and the FAK inhibitor PF-431396 (PF). Gene expression and kinase activation were analyzed with quantitative molecular biology assays. PF effects were tested in the passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), and allergic conjunctivitis (AC) mouse models. Our results showed that FAK overexpression increased IgE-mediated degranulation and reduced the dexamethasone inhibitory effect on MCs activation. The FAK inhibitor PF diminished MC release of ß-hexosaminidase (ß-hex), histamine, and inflammatory cytokines, via a mechanism that involves MAPK and NF-κB signaling pathways. CaMKII was identified as a robust FAK-associating protein. Inhibition of CaMKII activation by KN-93 suppressed FAK activity and its downstream pathway. PF attenuated inflammatory responses in our PCA and ASA models, and relieved signs of allergic disease in AC model mice. In conclusions, MC degranulation and production of inflammatory mediators in allergic disease may be consequent to FcεRI crosslinking inducing CaMKII-mediated activation of FAK activity. FAK inhibition may represent a new MC-suppressing treatment strategy for the treatment of allergic diseases.

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis.

BACKGROUND: Activator protein-1 (AP1), a c-Fos-JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses. METHODS: In vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with ß-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease. RESULTS: c-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by ß-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice. CONCLUSION: IgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.

Notes on the species of Abrostola Ochsenheimer, 1816 (Lepidoptera, Noctuidae, Plusiinae) from China, with the description of a new species.

This paper deals with seven species of Abrostola from China, among which one is new to science. The new species, Abrostola wanglangensis sp. nov., resembles Abrostola korbi Dufay, 1958 (known from Russia) and Abrostola pacifica Dufay, 1960 (known from Russia, Korean Peninsula and Japan). Adults and genitalia are illustrated.

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) sponges microRNA-124-3p to up-regulate phosphodiesterase 4B (PDE4B) to accelerate the progression of Parkinson's disease.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson's disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) -124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Early MRI imaging and follow-up study in cerebral amyloid angiopathy.

AIM: To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients. METHODS: The earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed. RESULTS: We found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group (p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS. CONCLUSION: LA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH.

The Usefulness of Pretreatment MR-Based Radiomics on Early Response of Neoadjuvant Chemotherapy in Patients With Locally Advanced Nasopharyngeal Carcinoma.

The aim of this study was to explore the predictive role of pretreatment MRI-based radiomics on early response of neoadjuvant chemotherapy (NAC) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Between January 2016 and December 2016, a total of 108 newly diagnosed NPC patients who were hospitalized in the Cancer Hospital of the University of Chinese Academy of Sciences were reviewed. All patients had complete data of enhanced MR of nasopharynx before treatment, and then received two to three cycles of TP-based NAC. After 2 cycles of NAC, enhanced MR of nasopharynx was conducted again. Compared with the enhanced MR images before treatment, the response after NAC was evaluated. According to the evaluation criteria of RECIST1.1, 108 cases were divided into two groups: 52 cases for the NAC-sensitive group and 56 cases for the NAC-resistance group. ITK-SNAP software was used to manually sketch and segment the region of interest (ROI) of nasopharyngeal tumor on the MR enhanced T1WI sequence image. The parameters were analyzed and extracted by using AI Kit software. ANOVA/MW test, correlation analysis, and LASSO were used to select texture features. We used multivariate logistic regressions to select texture features and establish a predictive model. The ROC curve was used to evaluate the efficiency of the predictive model. A total of 396 texture features were obtained by using feature calculation. After all features were screened, we selected two features including ClusterShade_angle135_offset4 and Correlation_AllDirection_offshe1_SD. Based on these two features, we established a predictive model by using multivariate logistic regression. The AUC of the two features used alone (0.804, 95% CI=0.6020.932; 0.762, 95% CI=0.5560.905) was smaller than the combination of these two features (0.905, 95% CI=0.7240.984, p=0.0005). Moreover, the sensitivity values of the two features used alone and the combined use were 92.9%, 51.7%, and 85.7%, respectively, while the specificity values were 66.7%, 91.7%, and 83.3%, respectively, in the early response of NAC for NPC. The predictive model based on MRI-enhanced sequence imaging could distinguish the sensitivity and resistance to NAC and provide new biomarkers for the early prediction of the curative effect in NPC patients.

Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.

[Population status and protection evaluation of Syzygium album, a species with extremely small population.] / 极小种群植物白果蒲桃种群现状与保护评价.

Syzygium album is a plant species with extremely small population and endemic to Yun-xiao County, Fujian Province. We examined its population status and conservation evaluation. The results showed that there were 25 individuals of S. album, with only one mother tree. Except for the mother tree and one small tree, the others were all young seedlings, which was rare in abundance and lack of age stage of middle and strong trees. The spatial distribution of young seedlings was not uniform, with most of individuals within the range of 10-25 m from the mother tree. The age class structure of the population was not continuous and the population development was unsustainable. The competition mainly came from other species. Cryptocarya chinensis accounted for 66.6% of the total competition index, which was much higher than other species. We established a comprehensive evaluation index system for the protection of rare and endangered plants with extremely small populations and evaluated the protection of S. album from three aspects, i.e., endangered degree, protection value, and protection priority. The endangered degree of S. album was level Ⅰ (the endangered degree index was 4.510), belonging to extremely endangered species, the protection value was level Ⅰ (the protection value index was 4.052), which was of great value, and the protection priority was level Ⅰ (the protection priority index was 4.016), which should be listed as the highest priority protection level.

Aberrant voxel-based degree centrality in Parkinson's disease patients with mild cognitive impairment.

The purpose was to explore the intrinsic dysconnectivity pattern of whole-brain functional networks in Parkinson's disease patients with mild cognitive impairment (PD-MCI) using a voxel-wise degree centrality (DC) analysis approach. The resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed in all subjects including PD-MCI, PD patients with no cognitive impairment (PD-NCI), and healthy controls (HCs). DC mapping was used to identify functional connectivity (FC) alterations among these groups. Correlation between abnormal DC and clinical features was performed. Secondary seed-based FC analyses and voxel-based morphometry (VBM) analyses were also conducted. Compared with HCs, PD-MCI and PD-NCI showed DC abnormalities mainly in the right temporal lobe, thalamus, left cuneus, middle frontal gyrus, and corpus callosum. Compared with PD-NCI, PD-MCI showed abnormal DC in the left fusiform gyrus (FFG) and left cerebellum lobule VI, left cuneus, right hippocampus, and bilateral precuneus. In PD-MCI patients, correlation analyses revealed that DC in the left FFG was positively correlated with the Montreal Cognitive Assessment (MoCA) scores, and DC in the left precuneus was negatively correlated with the MoCA scores. Secondary seed-based FC analysis further revealed FC changes mainly in the default mode network, right middle cingulum, right supramarginal gyrus, and right postcentral/precentral gyrus. However, no significant difference was found in the secondary VBM analysis. The findings suggest that dysfunction in extensive brain areas is involved in PD-MCI. Among these regions, the left precuneus, FFG, and cerebellum VI may be the key hubs in the pathogenesis of PD-MCI.

Optimal induction chemotherapeutic regimen followed by concurrent chemotherapy plus intensity-modulated radiotherapy as first-line therapy for locoregionally advanced nasopharyngeal carcinoma.

For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), induction chemotherapy (IC) regimens based on TPF (docetaxel, cisplatin, and 5-fluorouracil), TP (docetaxel and cisplatin), and GP (gemcitabine and cisplatin) have shown excellent survival outcomes as the first-line therapy; however, no trials comparing the efficacy and safety of TPF, TP, and GP have been reported. We report 2 phase II trials comparing the treatment outcomes and side effects of 3 different IC regimens followed by concurrent chemoradiotherapy in locoregionally advanced patients with NPC.A total of 206 locoregionally advanced patients with NPC treated with a combination treatment from January 2012 to January 2014 were enrolled in the 2 studies. The patients received TPF-, TP-, and GP-based IC regimens every 3 weeks, followed by intensity-modulated radiotherapy and concurrent therapy with cisplatin every 3 weeks.After a median follow-up duration of 47 months (10-60 months), the 3-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival rates were 96.4%, 100%, 87.7%, 86%, and 94.7% in the TPF arm; 91.7%, 95.9%, 91.9%, 85.2%, and 92% in the TP arm; 98.6%, 100%, 89.0%, 87.6%, and 89.2% in the GP arm. The survival differences among the 3 arms were not statistically significant (P > .05). The multivariate analysis demonstrated that the IC regimen was not an independent prognostic factor for any survival outcomes. The patients in the TP arm experienced significantly lower grade 3/4 toxicities than the patients in the other 2 arms.TP-based IC regimen has similar efficacy compared with TPF- and GP-based IC regimens; however, TP-based IC regimen has a lower toxicity profile.

Structural and Functional Thalamic Changes in Parkinson's Disease With Mild Cognitive Impairment.

BACKGROUND: The thalamus is a key node of deep gray matter and previous studies have demonstrated that it is involved in the modulation of cognition. PURPOSE: To investigate the volume changes of the thalamus and its subregions and altered thalamus functional connectivity patterns in Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI). STUDY TYPE: Prospective. POPULATION: Thirty-three patients with MCI (PD-MCI), 36 PD patients having no cognitive impairment (PD-NCI), 21 healthy controls (HCs). SEQUENCE: 3.0T MRI scanner; 3D T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); resting-state fMRI ASSESSMENT: Voxel-based morphometry (VBM) was performed to calculate the volume of the thalamus and its subregions. The left and right total thalamus were considered seeds and seed-based functional connectivity (FC) was analyzed. Additionally, correlations between volumes and cognitive performance and between FC values and cognitive performance were examined separately. STATISTICAL TEST: Analysis of covariance (ANCOVA); two-sample t-tests; partial correlation analysis. RESULTS: The volumes of the total thalamus (PD-MCI vs. PD-NCI vs. HCs: 18.39 ± 1.67 vs. 19.63 ± 1.79 vs. 19.47 ± 1.35) and its subregions were significantly reduced in PD-MCI as compared to PD-NCI (total thalamus: P = 0.002) and HCs (total thalamus: P = 0.012). Compared with PD-NCI, PD-MCI showed increased FC between the thalamus and bilateral middle cingulate cortex and left posterior cingulate cortex, and decreased FC between thalamus and the left superior occipital gyrus, left cuneus, left precuneus, and left middle occipital gyrus. Volumes of thalamus and the subregions, as well as the FC of thalamus with the identified regions, were significantly correlated (P < 0.05, FDR-corrected) with neuropsychological scores in PD patients. DATA CONCLUSION: We noted volume loss and altered FC of thalamus in PD-MCI patients, and these changes were correlated with global cognitive performance. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICIENCY: Stage 2 J. Magn. Reson. Imaging 2020;52:1207-1215.

Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic immunological response to Aspergillus fumigatus (Af) exposure, which induces a strong T helper 2 (Th2) response via mechanisms that have yet to be elucidated. The aim of the present study was to investigate the hypothesis that T2 ribonuclease from Af (Af RNASET2) induces M2­type macrophage polarization to produce a T helper 2 (Th2) immune response. Recombinant Af RNASET2 (rAf RNASET2) was expressed and purified in a prokaryotic pET system and BALB/c mice were immunized with rAf RNASET2 for in vivo analyses. Expression levels of M2 polarization factors were evaluated in RAW264.7 macrophages treated with rAf RNASET2 in vitro using flow cytometry, reverse transcription­quantitative PCR, and western blot analysis. The results predicted that the mature Af RNASET2 protein (382 amino acids; GenBank no. MN593022) contained two conserved amino acid sequence (CAS) domains, termed CAS­1 and CAS­2, which are also characteristic of the RNASET2 family proteins. The protein expression levels of the Th2­related cytokines interleukin (IL)­4, IL­10, and IL­13 were upregulated in mice immunized with rAf RNASET2. RAW264.7 macrophages treated with rAf RNASET2 showed increased mRNA expression levels of M2 factors [arginase 1, Il­10, and Il­13]; however, there was no difference in cells treated with rAf RNASET2 that had been inactivated with a ribonuclease inhibitor (RNasin). The protein expression levels of IL­10 in macrophage culture supernatant were also increased following stimulation with rAf RNASET2. In addition, rAf RNASET2 upregulated the expression of phosphorylated mitogen activated protein kinases (MAPKs) in RAW264.7 cells, whereas MAPK inhibitors attenuated rAf RNASET2­induced IL­10 expression in RAW264.7 cells. In conclusion, the present study reveals that high rAf RNASET2 activity is required for rAf RNASET2­induced M2 polarization of macrophages and suggests an important immune regulatory role for Af RNASET2 in ABPA pathogenesis.