Objective To investigate the reproducibility and consistency in contouring parotid gland volume based on computed tomography (CT) and magnetic resonance (MR) images in patients with nasopharyngeal carcinoma during radiotherapy.Methods Twenty-seven patients with nasopharyngeal cancer in Shandong Cancer Hospital from December 2012 to May 2013 were randomly enrolled and underwent intensified CT and MR imaging before radiotherapy.The parotid gland were contoured with unified standard on both CT and T1-MR images by 11 radiotherapists.Specifically,one radiotherapist sketched the parotid gland on CT and MR images for ten times as intra-group comparison,the other ten were asked to sketch the parotid gland on CT and MR images only once as inter-group comparison.The intra-and inter-group's variations of parotid gland volumes were analysed.Results The average volumes of intra-group on CT and MR images were (33.8 ±9.4) cm3(L),(33.2±7.6) cm3(R) and (24.4 ±7.6) cm3(L),(22.5 ±7.4) cm3(R).As well,for inter-group the average volumes were (34.6 ± 12.1) cm3 (L),(34.3 ± 9.0) cm3 (R) and (24.6 ± 7.6) cm3 (L),(23.2 ± 8.1) cm3(R),respectively.The volume variable ratios on CT images were (6.8 ± 1.5)％ (L),(6.3 ± 1.5) ％ (R) for intra-group and (18.0 ± 4.8) ％ (L),(17.4 ± 4.6) ％ (R) for inter-group.Similarly,the intra-and inter-group ratios for contouring on MR images reached (2.3 ±0.4)％ (L),(2.1 ±0.7)％ (R) and (4.7 ±0.7)％ (L),(5.0±0.6)％ (R),respectively.Conclusion Parotid gland contouring based on MR images has a better reproducibility and consistency than that based on CT images.It is beneficial to get a more objective and true indicator to estimate the radiation injury of parotid gland.

Objective To determine the efficacy and safety of Chinese Medicine Jiaweidingchuan Soup in the treatment of asthma.MethodsPatients(n =32)with mild-to-moderate asthma were treated with Chinese Medicine Jiaweidingchuan Soup for 4 weeks.We measured the FVC、FEV1、PEF、IL-6 and IFN-? level.ResultsAfter treatment,the FVC、FEV1 and PEF values and the expression of IFN-? in patient with asthma increased significantly(P

Objective To investigate a feasibility of treatment planning in thoracic esophageal carcinoma with 3-deoxy-3-fluorothymidine (FLT) PET-CT and to compare with fluorodeoxyglucose (FDG) PET-CT based on dosimetric analysis.MethodsTwenty-two patients with esophageal squamous cell carcinoma detected by FLT and FDG PET-CT were enrolled.The gross tumor volumes ( GTV ),clinical target volume(CTV) and planning target volume ( PTV ) were delineated using treatment planning system of Philips Pinnacle3 based on the optimal threshold of FLT and FDG PET-CT respectively,and to make two groups simulation treatment planning.The parameters of dose-volume histograms in two groups planning were compared in the similar direction and ensuring prescribed dose line surround 95% target volume.Results The values of GTV,CTV and PTV in FLT PET-CT planning were less than those of FDG,that dose received by spinal cord in two planning were not significantly yet ( t = - 1.60,- 1.55,all P ＞ 0.05 ).While,the values in mean lung dose,V5,V10,V30,V40 and V50 of bilateral lung,mean heart dose,and V30 of heart in FLT PET-CT planning were significant lower than those of FDG( t = -5.442 - -2.637,all P ＜0.05).Conclusions Compared with FDG,FLT PET-CT based treatment planning brings potential benefits for lungs and heart.

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol(TCL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG)]and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD (r=-0.34,P<0.001) and RA (r=-0.36,P<0.001). Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.

Objective: To analyze the incidence and microbiological features of blood stream infections (BSI) of patients with hematopoietic stem cell transplantation (HSCT) and to provide laboratory data for empirical use of antibiotic for the HSCT patients with BSI. Methods: The incidence of bloodstream infection, the positive rate of blood culture, bacterial spectrum and drug resistance were analyzed in 1 265 HSCT recipients during 2013 and 2015 were retrospectively studied. Results: Of 1265 patients undergoing HSCT, 1 422 cases of suspected BSI occurred in 784 patients (61.98%) , and 464 patients (59.2%) were in the stage of agranulocytosis (ANC<0.5×10⁹/L) . The detection rate of pathogens in 2013-2015 was about 20% and increase year after year. Of the 401 strains detected, 221 were Gram-negative (G^-) bacteria (55.1%) , 165 Gram-positive (G⁺) bacteria (41.2%) and 15 fungi (3.7%) . Escherichia coli (16.0%) , Staphylococcus epidermidis (15.5%) and Klebsiella pneumoniae (11.2%) were listed the top three. The proportion of multidrug resistant Acinetobacter Bauman and Stenotrophomonas maltophilia was 64.70% and 63.64% respectively, and methicillin resistant Staphylococcus aureus (MRSA) was more than half (57.14%) . The ratio of vancomycin resistant Enterococci (VRE) and carbapenem resistant Enterobacteriaceae (CRE) was 14.29% and 6.78% respectively. More than 40% Enterobacteriaceae bacteria were resistant to three or four generation cephalosporin antibiotics, and less were resistant to the carbapenems (6.4%) . However, many non-fermentating bacteria were highly resistant to these antibiotics and showed diversity among different strains, with a rate of 47.8% resistance to carbapenems. All the Staphylococcus were sensitive to vancomycin, teicoplanin and linezolid. Conclusions The incidence of BSI in patients with HSCT was high, and the pathogens were mainly G^- bacteria. In addition to Enterobacteriaceae, the proportion of non-fermentative bacteria was quite high. No Staphylococcus detected were resistant to vancomycin, teicoplanin and linezolid.

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.
Bacterial Proteins/metabolism* ; Bacterial Toxins/metabolism* ; Caco-2 Cells ; Clostridioides ; Clostridioides difficile/genetics* ; Humans ; Oxidoreductases/metabolism* ; Transcriptome ; Vaccines, Attenuated

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified