Comparing biofilm reactors inoculated with Shewanella for decolorization of Reactive Black 5 using different carrier materials.

This study assessed the performance of biofilm reactors inoculated with azo dye degrading Shewanella for the decolorization of Reactive Black 5 (RB5), using three different carrier materials, namely almond shell biochar, moving bed biofilm reactor (MBBR), and polypropylene carrier (PPC). The reactors were fed with low-nutrient artificial wastewater containing RB5, and all three carriers showed good RB5 decolorization performance, with varying efficiencies. Liquid Chromatography-Mass Spectrometry analysis revealed distinct RB5 degradation pathways associated with each carrier, influenced by carrier materials and microbial communities. The MBBR carrier exhibited good stability due to its rough surface and microbial aggregates. Sequencing results highlighted differences in the microbial community structures among the carriers. Shewanella predominated the functional bacteria in the MBBR and PPC carriers, while the biochar carrier fostered highly efficient degrading microbial communities. The physicochemical properties of carrier materials significantly influenced the microbial community and RB5 degradation efficiency. These findings provide valuable insights for optimizing biofilm reactors for dye-containing wastewater treatment.

Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study.

Background: Immune checkpoint inhibitors (ICIs) have changed the therapeutic options for extensive-stage small-cell lung cancer (ES-SCLC). In this real-world study, we analyzed the treatment patterns in patients with ES-SCLC and evaluated the efficacy of chemotherapy combined with immunotherapy as first-line therapy. Methods: A retrospective analysis was performed on patients with ES-SCLC who received treatment at China-Japan Friendship Hospital (Beijing, China) between August 1, 2020, and April 30, 2023. The treatment patterns appeared in the form of Sunburst Chart and Sankey diagram. The survival analyses were conducted by Kaplan-Meier curves. Results: A total of 157 patients with ES-SCLC were retrospectively included. According to first-line therapy, patients were divided into the chemotherapy (CT) group (n=82) and chemo-immunotherapy (CIT) group (n=75). The median treatment lines were 2[1, 2] and cycles were 8[5, 12], respectively. 82 patients received the second line of therapy, followed by 37 for the third, 15 for the fourth, 11 for the fifth, and 5 for the sixth. Overall, the treatment patterns involved 11 options including 12 chemotherapy regimens, 11 ICIs, and 4 targeted agents. The second-line treatment pattern had the most options (9) and regimens (43). In the first 3 lines, chemotherapy was the largest proportion of treatment options. The addition of ICIs prolonged progression-free survival from 6.77 (95% confidence interval [CI], 6.00-7.87) to 7.33 (95% CI, 6.03-9.80) months (hazard ratio [HR]=0.67, 95% CI, 0.47-0.95; P=0.025), overall survival from 12.97 (10.90-23.3) to 14.33 (12.67-NA) months without statistically significant difference (HR=0.86, 95% CI, 0.55-1.34; P=0.505). Conclusion: The treatment options of patients with ES-SCLC are more diversified. Combination therapy is the current trend, where chemotherapy is the cornerstone. Meanwhile, ICIs participate in almost all lines of treatment. However, the clinical efficacy remains barely satisfactory. We are urgently expecting more breakthrough therapies except immunology will be applied in the clinic.

Treatment-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors in advanced lung cancer: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) with angiogenesis inhibitors have been used to treat advanced lung cancer. Their associated treatment-related adverse events (trAEs) are currently considered acceptable; however, no conclusion has been reached. We aimed to summarize the trAEs caused by ICIs combined with angiogenesis inhibitors in patients with advanced lung cancer. METHODS: Pulled studies met the following criteria: patients with advanced lung cancer who received treatment involving ICIs combined with angiogenesis inhibitors (with or without chemotherapy) in interventional or observational studies. Results included the type and number of trAEs or immune-related adverse events (irAEs), treatment-associated discontinuation and mortality, overall survival (OS), and progression-free survival (PFS). PROSPERO: CRD42022337656. RESULTS: The study enrolled 32 trials involving 2313 patients who had 7768 any-grade trAEs and 1078 grade ≥3 trAEs. The pooled incidences were 87.33% (95% confidence interval [CI]: 79.49-93.65; I2 = 94.04%) for any-grade trAEs, and 38.63% (95% CI: 28.28-49.50; I2 = 95.61%) for grade ≥3 trAEs. There were 132 kinds of any-grade trAEs involving 18 systems, and 99 kinds of grade ≥3 trAEs involving 16 systems. For all trAEs, we observed significant differences in the line of therapy, trial design, therapy combination, and types of angiogenesis inhibitors (all P < 0.05). The rate of trAEs increased with dosage and frequency of medication. Pooled incidences of discontinuation and mortality were 10.64% and 0.81%, respectively. Nearly 647 patients experienced irAEs, including 636 any-grade irAEs and 154 grade ≥3 irAEs. CONCLUSIONS: Overall, the incidence of trAEs caused by ICIs combined with angiogenesis inhibitors is generally acceptable. These trAEs have a wide spectrum nearly covering the full range of adverse events. Grade ≥3 trAEs are more closely associated with angiogenesis inhibitors than any grade. However, treatment-associated mortality remains concerning.

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis B or C: A Systematic Review and Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods: The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results: A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion: According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.

Diagnostic value of quantitative myocardial blood flow assessment by NaI(Tl) SPECT in detecting significant stenosis: a prospective, multi-center study.

OBJECTIVES: The aim of this prospective multi-center study was to investigate the diagnostic value of myocardial blood flow (MBF) quantification using NaI(Tl)-based single-photon emission computed tomography (SPECT) for determining coronary artery disease (CAD) defined by quantitative coronary angiography (QCA). BACKGROUND: Absolute quantitation of MBF and myocardial flow reserve (MFR) using SPECT is clinically feasible; however, whether flow quantification using NaI(Tl) SPECT is superior to commonly performed SPECT myocardial perfusion imaging (MPI) in determining CAD has not been evaluated. METHODS: Patients with suspected or known CAD underwent pharmacological stress/rest dynamic SPECT imaging and routine SPECT MPI followed by QCA. Obstructive disease was defined as ≥ 50% reduction in luminal diameter on QCA. RESULTS: One hundred fifty-four patients (462 vessels) were included in the analysis. Obstructive CAD was detected in 76/154 patients (49.4%) and 112/462 vessels (24.2%). Optimal cut-off values were 1.86 mL/min/g for stress MBF and 1.95 for MFR, respectively. Stress MBF and MFR were more sensitive than MPI in both individual patients (stress MBF vs MPI: 81.6% vs 51.3%; MFR vs MPI: 72.4% vs 51.3%) and in coronary vascular regions (stress MBF vs MPI: 78.6% vs 31.3%; MFR vs MPI: 75.9% vs 31.3%; all P < .01). In receiver operating characteristic curve analysis, quantification revealed a significantly greater area under the curve than MPI at the patient (stress MBF vs MPI: 0.761 vs 0.641; MFR vs MPI: 0.770 vs 0.641) and the vessel (stress MBF vs MPI: 0.745 vs 0.613; MFR vs MPI: 0.756 vs 0.613; all P < .05) levels. Integrating quantitative SPECT measures with MPI significantly increased the area under the curve and improved the discriminatory and reclassification capacity. CONCLUSION: Flow quantification using NaI(Tl) SPECT provides superior sensitivity and discriminatory capacity to MPI in detecting significant stenosis. Clinical trial registration NCT03637725.

Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases.

Human diseases are characterized by intricate cellular dynamics. Single-cell sequencing provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in-silico drug interventions. Here, we introduce UNAGI, a deep generative neural network tailored to analyze time-series single-cell transcriptomic data. This tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modeling and discovery. When applied to a dataset from patients with Idiopathic Pulmonary Fibrosis (IPF), UNAGI learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation via proteomics reveals the accuracy of UNAGI's cellular dynamics analyses, and the use of the Fibrotic Cocktail treated human Precision-cut Lung Slices confirms UNAGI's predictions that Nifedipine, an antihypertensive drug, may have antifibrotic effects on human tissues. UNAGI's versatility extends to other diseases, including a COVID dataset, demonstrating adaptability and confirming its broader applicability in decoding complex cellular dynamics beyond IPF, amplifying its utility in the quest for therapeutic solutions across diverse pathological landscapes.

SPECT findings on neuropsychiatric symptoms caused by nitrous oxide abuse.

Objective: The aim of the study was to investigate the clinical, neuropsychological, and regional cerebral blood flow (rCBF) perfusion changes in patients with neuropsychiatric symptoms caused by nitrous oxide (N2O) abuse. Methods: A total of 16 patients with neuropsychiatric symptoms caused by nitrous oxide abuse were recruited for this study. The study was carried out in the withdrawal phase of N2O abuse. A 925-1110 MBq 99mTc-ECD was administered intravenously. SPECT/CT images were collected with a low-energy and high-resolution collimator. The region uptake statistics of different brain regions of interest between patients with N2O abuse and normal people of the databases for younger subjects from the Scenium DB Comparison software were calculated automatically. Results: The clinical manifestations of the 16 patients with neuropsychiatric symptoms were mood lability, anxiety, hallucination, delusion, agitation, confusion, and other psychiatric symptoms. In addition, 15 of the patients also complained of memory decline; 14 patients manifested numbness or paresthesia; 14 patients developed limb weakness, and their motor impairments were more severe in the lower limbs than in the upper limbs; and eight patients had urinary and defecation disturbances. In the neuropsychological examination, the BPRS score was 54.69 ± 11.48, the HAMD score was 30.00 ± 11.06, the HAMA score was 18.06 ± 5.77, the MMSE score was 28.06 ± 2.29, and the MoCA score was 25.06 ± 3.40. SPECT showed hypoperfusion in the frontal and temporal lobes, which is consistent with the clinical findings. Conclusion: This was the first study to demonstrate the obvious effect of N2O abuse on CBF in patients with neuropsychiatric symptoms. CBF perfusion imaging is helpful to detect the changes in the local brain functional activity in patients with N2O abuse.

lncRNA NEAT1 promotes autophagy of neurons in mice by impairing miR-107-5p.

This work focused on the exploration of NEAT1 in Parkinson's disease (PD) and aimed to explore its effects on PD and related molecular mechanisms. Two experimental models were initially constructed, including MPTP-induced mice in vivo and the MPP+-induced SH-SY5Y cell line in vitro. Immunofluorescence assays were conducted to determine the TH+ positive cell rate. Pole tests and rotarod tests were also performed for the visualization of behavioral changes in mice. Cellular apoptosis was determined using MTT and flow cytometry assays. Changes in the number of autophagosomes were obtained under a transmission electron microscope. The content of dopamine was confirmed by high performance liquid chromatography. The targeted interrelationship between miR-107-5p and NEAT1 was clarified via dual-luciferase reporter gene assays. Meanwhile, mRNA and protein expressions were also detected using qRT-PCR and Western blot respectively. Furthermore, the level of NEAT1 was positively correlated with MPP+ concentration. Interfering with NEAT1 in the present study promoted cellular proliferation and mediated SH-SY5Y cell apoptosis and autophagy treated with MPP+. An increase was discovered in TH positive neurons and suppressive autophagy in PD mice. miR-107-5p was then considered as a NEAT1 putative target involving apoptosis and autophagy of SH-SY5Y cells. Interfering with NEAT1 efficiently facilitated the viability of SH-SY5Y cells and drastically suppressed autophagy and apoptosis of PD mice induced by MPTP- via elevating miR-107-5p level, which indicated that lncRNA NEAT1 acted as a latent therapeutic factor for PD treatment.

Characterizing the hyper- and hypometabolism in temporal lobe epilepsy using multivariate machine learning.

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

High Inflammatory Tendency Induced by Malignant Stimulation Through Imbalance of CD28 and CTLA-4/PD-1 Contributes to Dopamine Neuron Injury.

BACKGROUND: Parkinson's disease is a common neurodegenerative disease in the elderly. The incidence of various cancers in Parkinson's disease patients is significantly lower than in healthy people. Parkinson's disease patients are individuals with a high tendency for inflammation, whose peripheral immune system is represented in an activated state. We hypothesized that the hyperinflammatory predisposition of Parkinson's disease patients is pathogenic. METHODS: DBA/1 mice were used to simulate "highly inflammatory individuals", and the carcinogen DEN was used to induce malignancy. Hematoxylin & eosin (H&E) staining was used to observe the formation of lung tumors. Apoptosis of neurons was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immunohistochemistry and flow cytometry were used to observe CD4, CD28, major histocompatibility complex II (MHCII), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and programmed death 1 (PD-1). The ionized calcium binding adaptor molecule-1 (IBA-1) + inducible nitric oxide synthase (iNOS) was used to label M1 microglia, and IBA-1 + arginase 1 (Arg1) was used to label M2 microglia by immunofluorescence. The expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and anti-inflammatory cytokines IL-10 and IL-4 was detected by ELISA. RESULTS: DBA/1 mice with high inflammatory tendency showed a continuous increase of peripheral inflammation, promoting intracranial inflammation, decreasing the tumor incidence and increasing the neurodegeneration under induction of malignant change. CD28 and CTLA-4/PD-1 reduced the T-cell-dominated inflammatory response, reduced the intracerebral inflammatory response, protected from neurodegeneration, and increased the incidence of tumor. Combination of CTLA-4 and PD-1 blocker can overactivate T cells, worsen peripheral and intracranial inflammation, reduce the incidence of tumor, cause damage to dopamine neurons, and promote the occurrence of neurodegeneration. CONCLUSION: High inflammatory tendency induced by malignant stimulation through the imbalance of CD28 and CTLA-4/PD-1 leads to dopamine neuron injury.

lncRNA NEAT1 prompts autophagy and apoptosis in MPTP-induced Parkinson's disease by impairing miR-374c-5p.

Long non-coding RNAs (lncRNAs) play biological roles in brain disorder and neurodegenerative diseases. As the functions of lncRNA NEAT1 in Parkinson's disease (PD) remain unknown, in the present study, we aimed to explore the roles and underlying molecular mechanisms of NEAT1 in PD. A PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and a cell model of SH-SY5Y induced by N-methyl-4-phenylpyridinium (MPP+) were established. The ratio of tyrosine hydroxylase (TH+) cells was determined by immunofluorescence assay, and the behavioral changes in mice were observed using pole tests and rotarod tests. The cellular viability and apoptosis of SH-SY5Y were detected by MTT assay and flow cytometric analysis, respectively, and the number of autophagosomes was subsequently measured by transmission electron microscopy. High-performance liquid chromatography was performed to detect the content of dopamine, and a dual-luciferase reporter assay was used to clarify the target of NEAT1 simultaneously. The results demonstrated that the level of NEAT1 was upregulated in the MPTP-induced PD mice, dopamine neurons, and the SH-SY5Y cells treated with MPP+, whereas the level of miR-374c-5p was downregulated. NEAT1 level was positively correlated with MPP+ in a concentration-dependent manner. NEAT1 inhibition efficiently facilitated cell proliferation but inhibited apoptosis and autophagy in the MPP+-treated SH-SY5Y cells. Additionally, silencing of NEAT1 increased the TH+ rate of neurons and suppressed autophagy greatly in PD mice. As a possible target of NEAT1, miR-374c-5p could impact on the apoptosis and autophagy of the SH-SY5Y cells. NEAT1 inhibition upregulated the expression of miR-374c-5p, enhanced SH-SY5Y cell viability, and repressed autophagy and apoptosis in MPTP-induced PD mice. These findings indicated a potential therapeutic role of NEAT1 in treating PD.

Ectopic Pancreatitis in the Gastric Antrum Mimicking Malignancy on FDG PET/CT.

ABSTRACT: A 34-year-old man suffered intermittent abdominal pain for 1 month, especially after drinking or eating. Enhancement CT was performed to determine the cause, which detected a soft tissue mass in the gastric antrum, suggestive of possible malignancy. FDG PET/CT scan was undertaken for staging, which showed increased metabolism in the known gastric mass, also suggestive of malignancy. However, this lesion was confirmed as ectopic pancreatitis pathologically.

Alterations of Cerebral Blood Flow Network in Behavioral Variant Frontotemporal Dementia patients with and without Apathy.

Apathy is one of the core symptoms in behavioral variant of frontotemporal dementia (bvFTD), and increases patient's morbidity and caregiver's distress. In this study, we applied a graph theoretical analysis (GTA) to analyze the topological properties of cerebral blood flow (CBF) network in 64 bvFTD patients with and without apathy (47 bvFTD-apathy and 17 bvFTD-woapathy, respectively), and 20 normal controls (NCs) based on single photon emission tomography (SPECT). Compared with the NCs, both the bvFTD groups preserved global function and typical features of small-worldness, but exhibited the loss of hubs mainly distributed in the prefrontal cortex (PFC). Compared with bvFTD-woapathy, the bvFTD-apathy group exhibited additional loss of hubs in the ventral PFC areas, middle cingulate cortex, limbic and paralimbic system, and subcortical regions, but recruited hubs in the areas of angular gyrus, precuneus and posterior cingulate cortex. Overall, our findings support the hypothesis that the disruption of frontostriatal circuit is associated with apathy in bvFTD.

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson's Disease.

OBJECTIVES: Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons in the substantia nigra. The present study investigated miR-141-3p/sirtuin1 (SIRT1) activity in a 1-methyl-4-phenylpyridinium- (MPP+-) induced PC12-cell model of PD. METHODS: PC12 cells were exposed to MMP+ following induction of differentiation by nerve growth factor (NGF). miR-141-3p and SIRT1 expressions were examined using RT-qPCR and western blot. Cell viability was evaluated using the MTT assay. Apoptosis percentage, reactive oxygen species (ROS) production, and mitochondrial membrane potential (Δψm) were evaluated using flow cytometry. Expression of Nuclear factor-kappa B- (NF-κB-) related proteins was determined by western blot. Bioinformatic analysis, RT-qPCR, and luciferase reporter assay were used to confirm the interaction between miR-141-3p and SIRT1. RESULTS: miR-141-3p was upregulated, and SIRT1 was downregulated in MPP+-treated PC12 cells. MPP+ treatment also upregulated nitric oxide synthase 1 (Nos1) and α-synuclein. miR-141-3p induced apoptosis, oxidative stress, mitochondrial dysfunction, and downregulated the SIRT1 mRNA expression. The luciferase reporter assay showed that SIRT1 was the target of miR-141-3p. SIRT1 transfection attenuated apoptosis, ROS production and maintained Δψm. SIRT1 also downregulated Nos1, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6(IL-6) and upregulated B cell lymphoma 2 (Bcl-2) protein. In addition, SIRT1 activator resveratrol blocked the effects of miR-141-3p mimic on Nos1, α-synuclein, and mitochondrial membrane potential. SIRT1 inhibitor sirtinol reversed the biological effects of miR-141-3p. CONCLUSION: Increased miR-141-3p induced apoptosis, oxidative stress, and mitochondrial dysfunction in MPP+-treated PC12 cells by directly targeting the SIRT1 expression. Our study provided a potential therapeutic strategy for PD.

Poly(A)-DG: A deep-learning-based domain generalization method to identify cross-species Poly(A) signal without prior knowledge from target species.

In eukaryotes, polyadenylation (poly(A)) is an essential process during mRNA maturation. Identifying the cis-determinants of poly(A) signal (PAS) on the DNA sequence is the key to understand the mechanism of translation regulation and mRNA metabolism. Although machine learning methods were widely used in computationally identifying PAS, the need for tremendous amounts of annotation data hinder applications of existing methods in species without experimental data on PAS. Therefore, cross-species PAS identification, which enables the possibility to predict PAS from untrained species, naturally becomes a promising direction. In our works, we propose a novel deep learning method named Poly(A)-DG for cross-species PAS identification. Poly(A)-DG consists of a Convolution Neural Network-Multilayer Perceptron (CNN-MLP) network and a domain generalization technique. It learns PAS patterns from the training species and identifies PAS in target species without re-training. To test our method, we use four species and build cross-species training sets with two of them and evaluate the performance of the remaining ones. Moreover, we test our method against insufficient data and imbalanced data issues and demonstrate that Poly(A)-DG not only outperforms state-of-the-art methods but also maintains relatively high accuracy when it comes to a smaller or imbalanced training set.

Evaluation of Lung Cancer and Neuroendocrine Neoplasm in a Single Scan by Targeting Both Somatostatin Receptor and Integrin αvß3.

PURPOSE: This pilot study aimed to prove the complementary value of a novel Gallium-labeled heterodimeric peptide, Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvß3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC). METHODS: With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent Ga-NOTA-TATE PET/CT, the SCLC patients underwent Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison. RESULTS: In the primary tumors of NSCLC, the T/B ratios of Ga-NOTA-3P-TATE-RGD were significantly higher than those of Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of Ga-NOTA-3P-TATE-RGD were significantly higher than those of Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of F-FDG (3.56 ± 0.74, P = 0.1833). CONCLUSIONS: This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan.

Regional cerebral blood flow correlates eating abnormalities in frontotemporal dementia.

BACKGROUND: Eating abnormalities are one of the core symptoms of frontotemporal dementia (FTD), especially for behavioral variant FTD (bvFTD), and semantic variant primary progressive aphasia (svPPA). METHODS: A group of FTD patients (43 bvFTD, 29 svPPA) underwent single-photon emission CT (SPECT) to measure the region cerebral blood flow (rCBF). The Cambridge Behavioral Inventory (CBI) was used to measure the eating abnormalities. A whole-brain voxel-based correlation between eating abnormalities and rCBF was investigated. RESULTS: In bvFTD, the sweet preference was correlated with decreased rCBF in the bilateral gyrus rectus and temporal pole, and eating the same food was correlated with the left ventral anterior cingulate cortex. In svPPA, decreased rCBF in the left inferior temporal gyrus was correlated with eating the same food. CONCLUSIONS: These findings showed that either different symptoms in the same subtype or the same symptom in different subtypes of FTD may be correlated with different regions, indicating different neural mechanisms behind them.

Oxytocin improves animal behaviors and ameliorates oxidative stress and inflammation in autistic mice.

OBJECTIVE: Autism is a neurodevelopmental disorder which significantly impacts the quality of people's life. Oxytocin is a hormone impacting the social cognition and interpersonal trust. In this study, we aimed to explore the role of oxytocin in autism. METHODS: Autistic mice models were established by valproate. Animal behaviors were assessed by open field test, tail suspension test, marble burying test and three-chamber social interaction test. Oxidative stress was evaluated by the levels or activities of malondialdehyde, superoxide dismutase, glutathion peroxidase, reduced glutathione and reactive oxygen species. Inflammation was assessed by the levels of tumor necrosis factor-α, interleukin-1ß and interleukin-6. The number of activated microglia was detected by immunofluorescence with an Iba-1 antibody. RESULTS: Our results showed that oxytocin improved the behaviors of autistic mice, with less anxiety, depression and repetitive behavior, and ameliorated social interaction. Further study showed that the elevated oxidative stress and inflammation in autistic mice were alleviated after treatment of oxytocin. CONCLUSION: Our study demonstrates that oxytocin treatment ameliorates autism in a mouse model, maybe through its modulation on oxidative stress and inflammation. It is indicated that oxytocin may beneficial to autism.

Rare malignant insulinoma with multiple liver metastases derived from ectopic pancreas: 3-year follow-up and literature review.

Here, we report the diagnosis and treatment of a very rare case of malignant insulinoma derived from ectopic pancreas. A middle-aged woman presented with a 6-year history of recurrent hypoglycemia with multiple lesions in liver. Admission workup revealed elevated serum insulin and C-peptide, as well as multiple lesions in the liver (largest being 4.3 cm), enlarged lymph nodes around the pancreas, and a lesion (of 3.5 cm) at the proximal jejunum, as shown by contrast computed tomography (CT). Liver biopsy showed the lesions to be well-differentiated neuroendocrine tumors, grade G1. 68Gallium-exendin-4 positron emission tomography/CT confirmed the origin as the lesion located at the jejunum. The combination treatment of everolimus plus long-acting octreotide relieved symptoms and achieved a partial tumor response. Maintenance treatment of the somatostatin analog (ie, octreotide) alone was administered. Three years of follow-up, up to the writing of this report, showed good survival, with the patient remaining asymptomatic and euglycemic without disease progression. This case shows that 68Gallium-exendin-4 positron emission tomography/CT is useful for locating insulinoma, especially for insulinoma derived from ectopic pancreas, and that everolimus plus octreotide with maintenance somatostatin analog alone is an effective drug strategy for treating inoperable malignant insulinoma.