Crosstalk in extrahepatic and hepatic system in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

Correlation of hypoxia as measured by fluorine-18 fluoroerythronitroimidazole (18F-FETNIM) PET/CT and overall survival in glioma patients.

PURPOSE: Hypoxia is important in the biology of glioma in humans. Positron emission tomography/computed tomography (PET/CT) with a hypoxia tracer offers a noninvasive method to differentiate individual tumor biology and potentially modify treatment for patients with malignancies. The purpose of this study was to determine whether hypoxia, as measured by fluorine-18 fluoroerythronitroimidazole (18F-FETNIM) PET/CT, was associated with tumor grade, overall survival (OS), and immunohistochemical features related to hypoxia, proliferation, angiogenesis, and the invasion of gliomas. PROCEDURES: Twenty-five patients with gliomas in whom gross maximal resection could be safely attempted were analyzed. All patients underwent 18F-FETNIM PET/CT studies before surgery. The maximum standardized uptake value (SUVmax) was obtained from the PET images of tumor tissues. Tumor specimens were stereotactically obtained for the immunohistochemical staining of hypoxia-inducible factor-1 alpha (HIF-1α), Ki-67, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9). RESULTS: A correlation between the SUVmax and glioma grade was found (r = 0.881, P < 0.001). The SUVmax was significantly correlated with the expression of HIF-1α, Ki-67, VEGF, and MMP-9 (r = 0.820, 0.747, 0.606, and 0.727; all P < 0.001). Patients with a high SUVmax had significantly worse 3-year OS than those with a low SUVmax (24.4% vs. 82.1%, P = 0.003). CONCLUSIONS: 18F-FETNIM PET/CT provides an excellent noninvasive assessment of hypoxia in glioma. It can be used to understand the mechanisms by which hypoxia affects the OS of glioma patients.

The α1-adrenergic receptor is involved in hepcidin upregulation induced by adrenaline and norepinephrine via the STAT3 pathway.

Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1-adrenergic receptor agonist), prazosin (PZ, α1-adrenergic receptor antagonist), and/or propranolol (Pro, ß-adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin-light (Ft-L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft-L protein and non-heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1-adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen.

A pilot study imaging integrin αvß3 with RGD PET/CT in suspected lung cancer patients.

PURPOSE: Angiogenesis is an essential step in tumour development and metastasis. Integrin αvß3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, (18)F-AL-NOTA-PRGD2, denoted as (18)F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvß3. This is a pilot study to test the safety and diagnostic value of (18)F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients. METHODS: Twenty-six patients with suspected lung cancer on enhanced CT underwent (18)F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed. RESULTS: RGD PET/CT with (18)F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The (18)F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of (18)F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100%, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 ± 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 ± 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to-blood ratio was significantly different between malignant lesions and inflammatory lesions or inflammatory pseudotumours (P > 0.05). Sixteen of 26 patients later underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 14 of 152 lymph nodes. The sensitivity, specificity, accuracy, PPV, and NPV of PET/CT for lymph nodes was 92.86, 95.65, 95.40, 61.90, and 99.25%, respectively. CONCLUSION: Our results suggest that RGD PET/CT with the new tracer (18)F-alfatide is safe and potentially effective in the diagnosis of non-small cell lung cancer. It may be used in the diagnosis of lung cancer, successfully distinguishing malignant lesions from hamartoma. However, it is difficult to clearly differentiate inflammatory or inflammatory pseudotumours from malignant lesions. Additional studies with a larger number of patients are needed to validate our findings.

Interscanner reproducibility of volumetric quantitative susceptibility mapping about cerebral subcortical gray nuclei at different MR vendors with the same magnetic strength.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) technique was a new quantitative magnetic resonance imaging technique to evaluate the cerebral iron deposition in clinical practice. The current study was aimed to investigate the reproducibility of the volumetric susceptibility value of the subcortical gray nuclei at two different MR vendor with the same magnetic strength. METHODS: Cerebral magnitude and phase images of 21 normal subjects were acquired from a 3D multiecho enhanced gradient recalled echo sequence at two different 3.0T MR scanner, and then the magnetic susceptibility images were generated by STI software. The brain structural images were coregistered with magnitude images and generated the normalized parameters, and then generated the normalized susceptibility images. The subcortical gray nuclei template was applied to extract the volumetric susceptibility value of the target nuclei. RESULTS: ICC value (95% CI) of the caudate, putamen and GP were 0.847 (0.660-0.935), 0.848 (0.663-0.935) and 0.838 (0.643-0.931), respectively. The ICC value of the thalamus was 0.474 (0.064-0.747). Ninety-five point two percent (20/21) of the difference points of the susceptibility located between the 95% LA for the caudate at the two different 3.0T MR scanner, while the less than 95% of the difference points of the susceptibility value located between the 95% LA for the putamen, globus pallidus and thalamus. CONCLUSION: The current study identified that the caudate had the stable reproducibility of the magnetic susceptibility value, and the other basal ganglion nuclei should be cautious for the quantitative evaluation of the magnetic susceptibility value at different 3.0T MR scanner.

Decreased Cerebral Perfusion in Chronic Migraine: A Voxel-based Cerebral Blood Flow Analysis Using 3D Pseudo-continuous Arterial Spin Labeling.

BACKGROUND: A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. METHODS: We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. RESULTS: Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). CONCLUSION: The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.

Hypoperfusion of Amygdala in Chronic Migraine: An Exploratory Quantitative Perfusion Imaging Using 3D Pseudo-Continuous Arterial Spin Labeling.

BACKGROUND: Although the amygdala has structural and functional abnormalities in Chronic Migraine (CM), less is known about the altered perfusion of the amygdala in CM. OBJECTIVE: The current study aimed to assess amygdala perfusion in CM using a contrast agent-free and quantitative approach. METHODS: 15 Normal Controls (NC) and 13 patients with CM during the migraine interval were assessed for brain structure and subjected to 3D Pseudo- Continuous Arterial Spin Labeling (3D-PCASL) MR imaging. The Cerebral Blood Flow (CBF) value of the amygdala was automatically extracted based on the individual amygdala mask for all participants. The independent sample t-test, Receiver Operating Characteristic (ROC) curve, and correlation analysis were used to evaluate the perfusion changes in CM. RESULTS: Bilateral amygdala cerebral perfusion was lower in CM (left amygdala, 42.21±4.49 ml/100mg/min; right amygdala, 42.38±4.41 ml/100mg/min) than in NC (left amygdala, 48.31±6.92 ml/100mg/min; right amygdala, 47.88±6.53 ml/100mg/min) (left, p = 0.01; right, p = 0.02). There was no significant correlation between the perfusion of bilateral amygdalas and the clinical variables. Also, there was no significant difference in the volume of bilateral amygdalas between the two groups. The Area Under the Curve (AUC) of the CBF values of the left and right amygdala was 0.78 (95%CI: 0.58-0.91) and 0.75 (95%CI: 0.55-0.89), respectively. The cut-off value was 44.24 ml/100mg/min (left amygdala, with sensitivity 76.90% and specificity 78.70%) and 46.75 ml/100mg/min (right amygdala, with sensitivity 92.3% and specificity 58.80%), respectively. CONCLUSION: CM presented bilateral hypoperfusion in the amygdala, offering potential diagnostic value in distinguishing CM from NC. The 3D-PCASL could be regarded as a simple and efficient neuroimaging tool to assess the perfusion status in CM patients.

Effects of Adding Sphingomonas Z392 to Drinking Water on Growth Performance, Intestinal Histological Structure, and Microbial Community of Broiler Chickens.

Probiotics are a prominent alternative to antibiotics in antimicrobial-free broiler farming. To assess the effect of Sphingomonas sp. Z392 (isolated and identified) on broiler growth, 600 one-day-old Kebao broiler chickens were randomly divided into a control group and an experimental group. Each group had three replicates, with 100 broiler chickens being raised in each replicate. Regarding the experimental group of broiler chickens, 4.0 × 105 CFU/mL of Sphingomonas Z392 was added to their drinking water. Then, the changes in broiler body weight, the EPI, intestinal histological structure, and gut microbiota were examined. The results show that the supplementation of the broilers' drinking water with 4 × 105 CFU/mL of Sphingomonas Z392 resulted in an increase in the relative abundance of Lactobacillus, Bacteroides, Lachnospiraceae, Aminobacterium, Oribacterium, Christensenellaceae, Faecalibacterium, Barnesiella, Ruminococcus, Parabacteroides, Phascolarctobacterium, Butyricicoccaceae, and Caproiciproducens, which have been reported to be positively correlated with the improved digestion and absorption of broiler chickens. The relative abundance of Odoribacter, Alistipes, Parabacteroides, and Rikenellaceae increased, and these have been reported to be negatively correlated with the occurrence of intestinal diseases. The relative abundance of Campylobacter, Shigella Castellani, Bilophila, Campylobacter, Clostridia, and Anaerotruncus decreased, and these have been reported to be positively correlated with the occurrence of intestinal diseases. At the same time, the following also increased: the integrity of small intestinal villus morphology; the number of goblet cells in small intestinal epithelial cells; the health of the mitochondria in the cytoplasm of jejunal villous epithelial cells; the number of lysosomes in the cytoplasm of goblet cells in the small intestinal epithelium, ileal villous epithelial cells, and mitochondria in the cytoplasm of large intestinal villous epithelial cells; the VH/CD of the ileum; and digestive, absorption, and defense capabilities. In particular, the final weight increased by 4.33%, and the EPI increased by 10.10%. Therefore, the supplementation of broiler drinking water with Sphingomonas generated better economic benefits from the broiler chickens.

Exploring the relationship between perceived social support and college students' autonomous fitness behavior: Chain mediating effect test.

Objective: This study aims to explore the effect of perceived social support on college students' autonomous fitness behavior, and the mediating role of mental toughness and exercise self-efficacy. Methodology: A survey participated by 985 college Students (average age, 19.55) was conducted by applying the following scales: The Perceived Social Support Scale, the Adolescent Self-Government Behavior Scale, the Mental Toughness Scale, and the Exercise Self-efficacy Scale (ESES). Results: (1) Perceived social support can directly and positively predict autonomous fitness behavior, mental toughness, and exercise self-efficacy; mental toughness can directly and positively predict exercise self-efficacy. Likewise, perceived social support, mental toughness, and exercise self-efficacy can positively predict autonomous fitness behavior. (2) The indirect effect of the path with mental toughness as the mediating variable is 0.078, the indirect effect of the path with exercise self-efficacy as the mediating variable is 0.122, and the indirect effect of the path with mental toughness and exercise self-efficacy as the mediating variable is 0.082. (3) The total of all indirect effects is 0.282, and the effects of the three indirect pathways account for 18.25, 28.62, and 19.37% of the total, respectively. Conclusion: The perceived social support can indirectly predict college students' autonomous fitness behavior through the independent mediating effect of mental toughness and self-efficacy, as well as the chain mediating effect of the two. The claim that mental toughness and exercise self-efficacy perform a chain-mediate role in the positive effect brought by perceived social support on autonomous fitness behavior has been supported. This study revealed the relationship and mechanism between perceived social support and college students' autonomous fitness behavior and further improved the research on the impact of perceived social support on college students' autonomous fitness behavior.

Potential 18F-RGD PET/CT and DCE-MRI Imaging-Based Biomarkers for Postoperative Survival Prediction Among Patients With Newly Diagnosed Glioblastoma Treated With Bevacizumab and Chemoradiotherapy.

Purpose: To investigate the ability of potential imaging biomarkers based on 18F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (18F-RGD PET/CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) imaging to predict the response to bevacizumab combined with conventional therapy in postoperative newly diagnosed glioblastoma. Methods: Twenty patients with newly diagnosed with glioblastoma after surgery were prospectively enrolled to receive bevacizumab plus conventional concurrent radiotherapy and temozolomide (CCRT). 18F-RGD PET/CT and DCE-MRI were performed at baseline, week 3, and week 10 for each patient. Statistical methods included the analysis of variance (ANOVA), Kaplan-Meier method and Cox proportional hazard analysis. Results: All patients completed CCRT plus bevacizumab therapy without interruption. The median follow-up time was 33.9 months (95% confidence interval [CI], 28.3-39.5 months). The median progression-free survival (PFS) and overall survival (OS) was 9.66 months (95% CI, 6.20-13.12 months) and 15.89 months (95% CI, 13.89-17.78), respectively. Treatment was generally well tolerated, and there were no Treatment emergent adverse events (TEAEs) with a toxicity grade equal to or exceeding 3 or that led to termination of treatment or patient death.Over the treatment interval of bevacizumab therapy from week 3 to week 10, patients with a large decrease of SUVmean was associated with a better PFS with a hazard ratio (HR) of 6.562, 95% CI (1.318-32.667), p=0.022. According to Kaplan-Meier analysis, patients with a decrease in the SUVmean of more than 0.115 on 18F-RGD PET/CT had a longer PFS than those with a decrease in the SUVmean of 0.115 or less (12.25 months vs.7.46 months, p=0.009). For OS, only a small decrease of Ktrans was also found to have certain prognostic value (HR=0.986, 95% CI (0.975-0.998), p=0.023). Patients with a decrease in Ktrans larger than 37.03 (min-1) on DCE-MRI had worse OS than those with a decrease in Ktrans of 37.03 (min-1) or less (15.93 months vs. 26.42 months, p=0.044). Conclusion: 18F-RGD PET/CT and DCE-MRI may be valuable in evaluating the response of glioblastoma to treatment with the combination of bevacizumab and CCRT, with a greater decrease in SUVmean predicting better PFS as well as a small decrease in Ktrans predicting improved OS.

[Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung cancer].

OBJECTIVE: To assess the feasibility of [(18)F]fluoroerythronitroimidazole ((18)F-FETNIM) with integrated positron emission tomography and computed tomography (PET-CT) imaging in detection of hypoxia in non-small-cell lung cancer (NSCLC) patients. METHODS: Forty-two patients with newly diagnosed NSCLC underwent (18)F-FETNIM PET-CT before treatment. Nineteen patients rested for approximately 120 minutes before undergoing PET-CT, 23 patients underwent 2 sequential PET-CT scans at 60 minutes and 120 minutes after intravenous injection (18)F-FETNIM. (18)F-FETNIM uptake was quantified by calculating the maximum standardized uptake value in the tumor (SUVmax-T) and contralateral normal lung tissue (SUVmax-N). Regions of interest (ROIs) were drawn in the tumor and contralateral position and the radioactivity ratio of tumor to normal (T/N) was calculated. RESULTS: SUVmax-T (2.43 +/- 1.34) was significantly higher than SUVmax-N (0.87 +/- 0.46, P < 0.001) at 120 min. SUVmax-T (2.80 +/- 1.09) and SUVmax-N (1.16 +/- 0.56) at 60 min were significantly higher than SUVmax-T (2.61 +/- 1.10) and SUVmax-N (P < 0.01) at 120 min. T/N (2.56 +/- 0.71) at 60 min was higher than that at 120 min (2.48 +/- 0.60), but the difference between them was not significant (P = 0.324). CONCLUSION: Our results indicate that (18)F-FETNIM PET-CT may be a useful tool for evaluating hypoxia and may be a means to target specifically tumor cells resistant to conventional treatment before and during ongoing therapy in NSCLC.

18F-RGD PET/CT imaging reveals characteristics of angiogenesis in non-small cell lung cancer.

BACKGROUND: The objective of this study was to explore the benefit of 18F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (denoted as 18F-RGD PET/CT) imaging for determining the clinical pathologic features of non-small cell lung cancer (NSCLC). METHODS: Seventy-two patients with NSCLC (37 cases of adenocarcinoma and 35 cases of squamous carcinoma) were enrolled to receive 18F-RGD PET/CT scanning pretreatment. The peak standard uptake value (SUVpeak), mean standard uptake value (SUVmean), angiogenic tumor volume (ATV) and total lesion angiogenesis (TLA) of tumors were determined using an automated contouring program. Cases were classified according to the tumor, lymph node, metastasis (TNM) stage. RESULTS: Significant differences in ATV and TLA were observed among T1, T2, T3 and T4 cases (ATV, P=0.000; TLA, P=0.000). ATV and TLA also differed significantly among cases of clinical stage I, II, III and IV (ATV, P=0.002; TLA, P=0.011). However, no significant differences in any values were observed between stage III and IV NSCLC cases (SUVpeak, P=0.675; SUVmean, P=0.668; ATV, P=0.52; TLA, P=0.634). All assessed values were higher in squamous cell carcinoma cases than in adenocarcinoma cases (SUVpeak, P=0.045; SUVmean, P=0.014; ATV, P=0.003; TLA, P=0.001). For clinical stage III and IV cases specifically, SUVpeak, SUVmean, and TLA were higher for squamous cell carcinoma than for adenocarcinoma (SUVpeak, P=0.015; SUVmean, P=0.009; TLA, P=0.036).Conclusions: 18F-RGD PET/CT imaging revealed the presence of increased angiogenesis in the tumor microenvironment of NSCLC, especially squamous cell carcinoma, and thus may be valuable in planning therapeutic regimens for individual patients.

PET-based biodistribution and radiation dosimetry of epidermal growth factor receptor-selective tracer 11C-PD153035 in humans.

UNLABELLED: The present study estimated the biodistribution and radiation-absorbed dose of epidermal growth factor receptor (EGFR) radioligand 11C-PD153035 in whole-body PET examinations of healthy volunteers. METHODS: Two-dimensional whole-body PET was performed on 9 subjects after injection of 11C-PD153035 at 329.3+/-77.8 MBq (mean+/-SD). A total of 12 frames were acquired for approximately 90 min in 7 segments of the body. Regions of interest were drawn on PET images of source organs. Residence time was calculated as the area under the time-activity curve. Radiation dosimetry was calculated from organ residence time by use of MIRDOSE3 software. RESULTS: The renal and hepatobiliary systems played important roles in 11C-PD153035 excretion from the body, accounting for the excretion of approximately 23% and 19% of the injected radioactivity, respectively. Blood-pool activity was only moderate and declined over time. Tracer accumulation in the lungs, bone marrow, and muscles was slight, resulting in low background activity in the chest. The organs with the highest radiation-absorbed doses were the urinary bladder and the gallbladder; the effective doses were 6.08E-02+/-1.85E-02 and 2.40E-02+/-8.01E-03 mGy/MBq, respectively. The effective dose equivalent was 7.43E-03+/-1.10E-03 mSv/MBq, and the dose-limiting organ was the urinary bladder. CONCLUSION: On the basis of the estimated absorbed dose, 11C-PD153035 displayed a favorable radiation dose profile in humans and therefore could be used in multiple PET examinations of the same subject per year. 11C-PD153035 is a promising ligand for the investigation of EGFR in humans, especially in chest tumors such as non-small cell lung cancer.

[Effects of different intensity interval exercise of 6 weeks on body composition of obese rats].

OBJECTIVE: To investigate the effects of different intensity intermittent exercise on the body function of obese rats, and to provide basis for the prevention and treatment of obesity. METHODS: Eighty SD rats were randomly divided into normal diet group (n=20) and high-fat diet group (n=60). After adaptive feeding for 8 weeks, 8 normal diet rats and 32 high-fat obese rats were selected for follow-up experiments. The experimental rats were randomly divided into 5 groups (n=8): control diet-sedentary (CS),with ordinary feed and without any exercise; high diet-sedentary (HS), with high-fat feed feeding and without any exercise; high diet-continual exercise(HC), 60 min/day,5 days/week with 6 weeks; high diet-long time-low frequency interval exercise(HLL), 30 min/time,twice/day (intermittent 6 h), 5 days/week with 6 weeks; high diet-short time-high frequency interval exercise(HSH), 20 min/ time, 3 times/d (intermittent 3 h), 5 days/week with 6 weeks. The training intensity of rats in each exercise group was 25 m/min. After 6 weeks, rats in each groups were weighed, and resting metabolic rate(RMR), fasting blood glucose(FBG), triglyceride(TG) and other biochemical indexes were detected, and fat and muscle weight were measured. RESULTS: Before experiment, there were no significant differences in RMR, FBG and TG in each groups(P＞0.05).The body weight of HSH, HLL, HC and HS groups was higher than that of CS group (P＜0.05). After the experiment, RMR of the HSH,HLL and HC groups was significantly higher than that of HS and CS groups (P＜0.05), but without significant difference among the HSH,HLL and HC groups (P＞0.05).The body weight of HSH, HLL and HC groups was significantly lower than that of HS group (P＜0.05), but the three groups was not significant (P＞0.05); perirenal fat(PF), idymis fat(EF), perirenal fat/weight(PF/W) and epididymis fat/weight(EF/W) of HSH, HLL, HC group were significantly lower than those of HS group (P＜0.01), while there was no statistical difference among the three groups (P＞0.05). There was no significant difference in gastrocnemius(GM) and quadricep(QF) of each group (P＞0.05), gastrocnemius/weight(GM/W) and quadriceps/weight (QF/W) in HSH,HLL and HC groups were higher than those of HS group (P＜0.05),while there was no significant difference among HSH,HLL and HC groups (P＞0.05);FEB,TG of HSH,HLL,HC group were lower than those of CS and HS group (P＜0.05),but the difference with HS group was more significant (P＜0.01),there was no significant difference among training groups(P＞0.05). CONCLUSION: 6 weeks of intermittent exercise of different intensity had a good intervention effect on the body composition of obese rats, and high diet-short time-high frequency interval exercise (HSH) may be more effective.

Hypoxia with 18F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (18F-FETNIM PET/CT) in locoregionally advanced head and neck cancer: Hypoxia changes during chemoradiotherapy and impact on clinical outcome.

Hypoxia is a well-recognized biological characteristic to therapy resistance and negative prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). This study aims to investigate the changes of hypoxia measured by F-fluoroerythronitroimidazole (FETNIM) uptake on integrated positron emission tomography and computed tomography (PET/CT) during chemoradiotherapy and its prognostic value of clinical outcome in locoregionally advanced HNSCC.Thirty-two patients with locoregionally advanced HNSCC who received definitive treatment with concurrent chemoradiotherapy underwent FETNIM PET/CT scans before and after 5 weeks of treatment. The intensity of hypoxia using the maximum standardized uptake value (SUVmax) was evaluated both on primary lesion and metastatic lymph node (MLN). The pre-SUVmax and mid-SUVmax were defined as SUVmax on pre- and mid-FETNIM PET/CT. The local control (LC), regional control (RC), distant metastatic-free survival (DMFS), and overall survival (OS) were collected in patient follow-ups.Mid-SUVmax decreased significantly both in the primary tumor (t = 8.083, P < .001) and MLN (t = 6.808, P < .001) compared to pre-SUVmax. With a median follow-up of 54 months, the 5-year LC, RC, DMFS, and OS rates were 55%, 66.7%, 64.7%, and 55%, respectively, for all of the patients. On univariate analysis, patients with high pre-SUVmax in primary tumor had significantly worse LC (56.3% vs 87.5%, P = .046) and OS (43.8% vs 87.5%, P = .023) than other patients. Patients with high mid-SUVmax had significantly worse DMFS (50% vs 84.6%, P = .049) and OS (33.3% vs 73.1%, P = .028) than other patients. The tumor grade and mid-SUVmax were the significant predictors of OS on multivariate analysis.In this study, hypoxia in tumor significantly decreased during chemoradiotherapy. The persistent hypoxia predicted poor OS. The data provided evidence that FETNIM PET/CT could be used dynamically for selecting appropriate patients and optimal timing of hypoxia-adapted therapeutic regimens.

[Molecular imaging of epidermal growth factor receptor in glioma-bearing rats].

OBJECTIVE: To investigate the value of 11C-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat. METHODS: The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography (PET/CT) scans started as soon as intravenous injection of 11C-PD153035 (15-20 MBq/0.3 ml) was completed, images were collected continuously. The region of interest (ROI) was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed. RESULTS: There were significant differences in 11C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order: liver > gastrointestinal tract > kidney > lung > brain > muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio (T/NT, target/non-target) peaked (4.15) at 40 - 50 min post injection. The in vitro blocking study showed that 11C-PD153035 uptaken by C6 cells could be blocked by PD153035. CONCLUSION: The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors. 11C-PD153035 has a potential as a bioprobe to yield useful information for both diagnosis and therapy of tumors. However, the high concentration of 11C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.

To Explore a Representative Hypoxic Parameter to Predict the Treatment Response and Prognosis Obtained by [18F]FMISO-PET in Patients with Non-small Cell Lung Cancer.

PURPOSE: To explore a representative hypoxic parameter to predict the treatment response and prognosis for [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET)/X-ray computed tomography (CT) in patients with non-small cell lung cancer (NSCLC). PROCEDURES: Twenty-nine patients with NSCLC underwent FMISO-PET scans before chemoradiotherapy (CRT). The maximum standard uptake values (SUVmax) in the tumor, normal lung, aortic arch, and vertical ridge muscle were measured, and the tumor-to-lung (T/L) ratios, tumor-to-blood (T/B) ratios, ands tumor-to-muscle (T/M) ratios were calculated and analyzed. Fractional hypoxic volume (FHV) was expressed as percentage of hypoxic volume. RESULTS: SUVmax, T/L ratio, T/B ratio, and FHV were all significantly different between the responders and the non-responders (SUVmax, 2.07 ± 0.53 vs. 2.61 ± 0.69, P = 0.026; T/L ratio, 3.16 ± 0.85 vs. 4.09 ± 1.46, P = 0.047; T/B ratio, 1.27 ± 0.20 vs. 1.48 ± 0.32, P = 0.042; 38.92 ± 18.47 vs. 52.91 ± 11.29 %, P = 0.020). However, the T/M ratio was not significantly different between the two populations (1.46 ± 0.31 vs. 1.67 ± 0.33, P = 0.098). The correlation ratio between hypoxic parameters and treatment responses ranged from high to low as FHV (r = 0.412); SUVmax (r = 0.400); T/L ratio (r = 0.379), P < 0.05; and T/B ratio (r = 0.355), P = 0.059. According to the area under curve (AUC) to predict response, the hypoxic parameters were arranged as FHV (AUC = 0.748), SUVmax (AUC = 0.731), T/L ratio (AUC = 0.719), and T/B ratio (AUC = 0.705). Binary logistic regression analyses showed that FHV was the only independent predictor for treatment response with the P value of 0.038. In the progression-free survival (PFS) prediction, both FHV and SUVmax reached statistical significance by Kaplan-Meier plots (FHV, 46.99 %, P = 0.010; SUVmax, 1.99, P = 0.046) while only FHV was the independent prognostic factor in multivariate analysis by Cox proportional hazard model (P = 0.037). CONCLUSION: FHV may be a representative hypoxic parameter to predict the CRT response and PFS in patients with NSCLC.

Further characterization of the epidermal growth factor receptor ligand 11C-PD153035.

BACKGROUND: (11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels. METHODS: Synthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter. RESULTS: Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001). CONCLUSIONS: The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.

[Effects of 4 week hypoxic training on endurance capacity and T lymphocyteofmale football players].

OBJECTIVE: To investigate the effects of 4-week hypoxia training on index related to endurance capacity and lymphocyte sub-jects of male football players. METHODS: Football players from a sport university were evenly divided into 4 groups:training group, hypoxic group, hypoxia training group and control group. The control group completed a 4-week cycling training with the intensity of 65%~75% VO2max, while the hypoxia training group did the same training in hypoxia environment (14.7% oxygen concentration);Low oxygen groups for 4 weeks daily 60 min, 5 times a week in a low oxygen (14.7% oxygen concentration) environment, did not cycle training;the control group without any intervention. RESULTS: In hypoxia training group, the red blood cell count and hemoglobin were significantly higher than those of the control group, training group and hypoxia group(P < 0.05);there was significant difference in VO2max and the performance of 3 000 m running between hypoxia training group and other groups(P < 0.05); the number of CD3+ level in hypoxia training group was significantly higher than that of the control group and hypoxia group (P < 0.05). CONCLUSIONS: Compared to other methods environment, a hypoxia training program of 60 min/d, 5 d/w, 4 weeks in total contributed to improve the endurance capacity of male football players, and it's also probably beneficial for improvement of immunity.

A novel molecular agent for glioma angiogenesis imaging.

BACKGROUND: Gliomas are rich in blood vessels and are the most primary and malignant type of brain tumor affecting the central nervous system. A few fluorine-18 (F)-labeled imaging agents can be used for imaging of tumor angiogenesis. In the current study, F-labeled recombinant human endostatin (rh-endostatin) was developed and evaluated as a probe for PET imaging of tumor angiogenesis. MATERIALS AND METHODS: F-fluorobenzoyl-endostatin (F-FB-endostatin) was synthesized from radiolabeling of rh-endostatin with N-succinimidyl-4-F-fluorobenzoate produced by a facile module-assisted radiosynthesis procedure. Blocking studies were used to measure the relative affinities of F-FB-endostatin to human glioblastoma U87MG cells in tumor tissues rich with vessels. In addition, biodistribution, metabolic stability, and small-animal PET imaging studies were carried out with F-FB-endostatin using Institute of Cancer Research and U87MG tumor-bearing mice. RESULTS: Noninvasive small-animal PET imaging indicated that F-FB-endostatin showed rapid and good tumor uptake. The probe was rapidly cleared from the blood and most organs, resulting in excellent tumor-to-normal tissue contrasts. Tumor uptake and rapid clearance were further confirmed with biodistribution studies. Metabolite assays showed that the probe was highly stable, making it suitable for in-vivo applications. CONCLUSION: F-FB-endostatin shows promising in-vivo properties. Therefore, the promising properties of F-FB-endostatin indicate that this probe can be a powerful tool to evaluate the antiangiogenic therapy for gliomas and thus warrants further investigation as a novel PET probe for imaging of tumor angiogenesis.