[Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-ß] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. RESULTS: Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. CONCLUSION: Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

Isolation and characterization of charge variants of infliximab biosimilar HS626.

Charge variants are the most commonly observed sources of heterogeneity in the routine manufacturing of monoclonal antibodies. To gain further insight into the structural foundation of charge heterogeneity and its influence on biological functions, an infliximab biosimilar HS626 from a biopharmaceutical facility was isolated by semipreparative cation exchange chromatography (CEX) to obtain fractions of acidic and basic charge variants and determine the main species. It was assessed again by CEX to ensure purities. Through a series of structural and physicochemical characterizations, we concluded that the acidic variants were caused by fragments, Met oxidation, Asn deamidation, higher levels of sialylation and galactosylation of N-linked glycans, and less high mannose. The basic variants resulted mainly from aggregates, fragments, and Met oxidation. Through further analysis of antigen binding affinity, cell death inhibitory activity, ADCC, and CDC, as well as FcRn, FcγRIIIa, and C1q affinity, we demonstrated that the charge heterogeneity did not affect biological functions. This research enhances the understanding of charge variants, which are usually effective components that should not be intentionally reduced unless biological functions are affected.

Molecular Spring-like Triple-Helix Coordination Polymers as Dual-Stress and Thermally Responsive Crystalline Metal-Organic Materials.

Elastic metal-organic materials (MOMs) capable of multiple stimuli-responsiveness based on dual-stress and thermally responsive triple-helix coordination polymers are presented. The strong metal-coordination linkage and the flexibility of organic linkers in these MOMs, rather than the 4 Šstacking interactions observed in organic crystals, causes the helical chain to act like a molecular spring and thus accounts for their macroscopic elasticity. The thermosalient effect of elastic MOMs is reported for the first time. Crystal structure analyses at different temperatures reveal that this thermoresponsiveness is achieved by adaptive regulation of the triple-helix chains by fine-tuning the opening angle of flexible V-shaped organic linkers and rotation of its lateral conjugated groups to resist possible expansion, thus demonstrating the vital role of adaptive reorganization of triple-helix metal-organic chains as a molecular spring-like motif in crystal jumping.

Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates.

In order to model various aspects of Huntington's disease (HD) pathology, in particular protein spread, we administered adeno-associated virus (AAV) expressing green fluorescent protein (GFP) or GFP coupled to HTT-Exon1 (19Q or 103Q) to the central nervous system of adult wild-type (WT) mice and non-human primates. All animals underwent behavioral testing and post-mortem analyses to determine the long-term consequences of AAV injection. Both mice and non-human primates demonstrated behavioral changes at 2-3 weeks post-surgery. In mice, these changes were absent after 3 months while in non-human primates, they persisted in the majority of tested animals. Post-mortem analysis revealed that spreading of the aggregates was limited, although the virus did spread between synaptically-connected brain regions. Despite circumscribed spreading, the presence of mHTT generated changes in endogenous huntingtin (HTT) levels in both models. Together, these results suggest that viral expression of mHTTExon1 can induce spreading and seeding of HTT in both mice and non-human primates.

Noncomplexed Cucurbituril-Mediated Structural Evolution of Layered Uranyl Terephthalate Compounds.

Template synthesis is one of the most feasible ways to explore new uranyl compounds with intriguing structures and properties. Here we demonstrate the preparation of six novel "sandwichlike" uranyl coordination polymers (UCPs) based on two-dimensional uranyl-terephthalate acid (H2TP) networks using CBn (n = 5, 6, 8) as template ligands in the presence of different cations (Na+, K+, Cs+, or H2N(CH3)2+). Compound 1 ([UO2(TP)2][Na2(CB5)(H2O)](H2O)5) is composed of layered uranyl-TP networks with the complex of CB5 and sodium cations as template ligands. In compound 2 ([(UO2)2(TP)3]2(CB6)(H2O)10), CB6 located between uranyl-TP networks contacts them by π-π interactions and hydrogen bonds. Compound 3 ([(UO2)2(TP)3]2[Na2(H2O)10(CB6)]) is the same as compound 2 except for sodium cations bonding with CB6. Similarly in compound 4 ([(UO2)2(TP)3][Cs(H2O)3(CB6)]), CB6 is a capsulelike structure capped with two cesium cations and interacts with uranyl-TP networks through π-π and C-H···π interactions. Compound 5 ([(UO2)2(TP)3(HCOO)2][K(H2O)2(CB5)]2[H2N(CH3)2]2(CB6)(H2O)6) consists of both templates of CB6 and CB5 in which each CB5 is capped with one potassium cation while the H2N(CH3)2+ cation is held at CB6 portals. In compound 6 ([(UO2)2(TP)3]2[UO2(TP)2(H2O)2][Cs(CB8)3(H2O)4](H2O)16), CB8 ligands are connected by cesium cations to form a triangle motif and are further located between the uranyl-TP networks as template agents. All of the 2D layered structures with free CBn or cation-anchored CBn intercalate into the laminates of uranyl-terephthalate and shows a cucurbituril-mediated structural evolution. The regulating role of CBn as structure-directing template agents for the construction of layered UCPs through outer-surface interactions with layers of uranyl terephthalate is demonstrated, especially for the case of CB6 with contractive interlayer spacing.

Detection of synergistic effect of superoxide dismutase and jujubosides on scavenging superoxide anion radical by capillary electrophoresis.

A new capillary electrophoresis method was developed to study the synergistic effect of superoxide dismutase and jujuboside A or B on scavenging superoxide anion radical in serum matrix respectively, in which superoxide anion radical was generated from pyrogallol autoxidation. The electrophoresis conditions, and the factors affecting the productive rate of purpurogallin, such as pyrogallol autoxidation product and the activity of superoxide dismutase, were optimized. Under optimal conditions, the content of superoxide dismutase in Gibco newborn calf serum was 7.06 mg/L, RSD was 2.01% and the average recovery was 98.4%. The values of IC50 for jujuboside A and B in the serum matrix were 157.67 and 31.60 mg/L respectively, and they both had synergy on scavenging superoxide anion radical with superoxide dismutase, but there was no the dose-dependency on this synergy.

Bipyridine-Directed Syntheses of Uranyl Compounds Containing Semirigid Dicarboxylate Linkers: Diversity and Consistency in Uranyl Speciation.

Bipyridine organic bases are beneficial to the synthesis of novel uranyl-organic hybrid materials, but the relationship between their molecular structures and specific roles as structure-directing agents, especially for the semirigid dicarboxylate systems, is still unclear. Here we demonstrate how the bipyridine ligands direct the coordination assembly of uranyl-organic compounds with a semirigid dicarboxylate linker, 4,4'-dicarboxybiphenyl sulfone (H2dbsf), by utilizing a series of bipyridine ligands, 1,10-phenanthroline (phen), 2,2'-bipyridine (2,2'-bpy), 5,5'-dimethylbipyridine (5,5'-dmbpy), 4,4'-bipyridine (4,4'-bpy), or 1,3-di(4-pyridyl)propane (bpp). Under hydrothermal conditions, eight uranyl-organic coordination polymers (UCPs), four of which [[UO2(dbsf)(phen)] (1), [UO2(dbsf)(phen)]·H2O (1'), [U4O10(dbsf)3]2[H2bpp]2 (6), and [U4O10(dbsf)3]2[H2bpp] (6')] were reported previously, were synthesized and divided into two types based on the chelate or template effect of these bipyridine ligands. 1, 1', [UO2(dbsf)(2,2'-bpy)] (2), and [(UO2)2(dbsf)2(5,5'-dmbpy)2] (3) are springlike triple helices with bipyridine ligands (phen, 2,2'-bpy, or 5,5'-dmbpy) as chelate ligands, while [U4O10(dbsf)3][H2(4,4'-bpy)] (4), [U4O10(dbsf)3]2[H(4,4'-bpy)]2[Ni(H2O)6] (5), 6, and 6' are tetranuclear uranyl-mediated 2-fold-interpenetrating networks with 4,4'-bpy or bpp as template ligands and charge-balancing agents. The participation or not in uranyl coordination of different bipyridine ligands promotes not only diversity in uranyl speciation and final topological structures among different classes of organic bases but also consistency for the same types of bipyridine ligands, which thus endows the possibility of the rational design of UCPs based on semirigid dicarboxylate ligands with the aid of cautiously selected bipyridine ligands.

Supramolecular Isomers of Coordination-Directed Side-Chain Polypseudorotaxanes Based on Trimeric Uranyl Oxalate Nodes.

Although the prosperity of rotaxane coordination polymers with rotaxane molecules serving as main-chain linkers is known, side-chain metal-organic polypseudorotaxanes incorporating macrocyclic host molecules have not been reported to date. Herein a new type of coordination-driven cucurbit[6]uril-bearing side-chain polypseudorotaxane, with two-dimensional trimeric uranyl-oxalate as main chains, has been synthesized. This was carried out through hydrothermal reactions of uranyl components with an in situ-formed carboxylated pseudorotaxane ligand in the presence of oxalate co-ligands. Varying the substitution site of coordination groups led to two different supramolecular isomers. Further mechanistic analysis indicated that condition-dependent hydrolysis of the cyano groups of the pseudorotaxane ligand, as well as the participation of oxalate groups into the coordination sphere of uranyl moieties, contributes to the formation of this new type of side-chain polypseudorotaxane.

The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10µg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity). Additionally, according to the enzyme-linked immunospot, intracellular cytokine staining, and cytometric bead array assays, significant and functional T-cell immunity was induced by 10µg of the rNTD vaccination with aluminum and CpG adjuvant. Furthermore, rNTD-immunized mice showed reduced lung abnormalities in a MERS-CoV-challenge mouse model transfected with an adenoviral vector expressing human DPP4, showing protection consistent with that found with rRBD vaccination. These data show that rNTD induced potent cellular immunity and antigen-specific neutralizing antibodies in mice and that it demonstrated protective capacity against a viral challenge, indicating that rNTD is a vaccine candidate against MERS-CoV infection.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

IL-17 protein levels in both induced sputum and plasma are increased in stable but not acute asthma individuals with obesity.

BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored. RESULTS: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain.

The templated synthesis of a unique type of tetra-nuclear uranyl-mediated two-fold interpenetrating uranyl-organic framework.

Two novel tetra-nuclear uranyl-mediated two-fold interpenetrating networks, [U4O10(dbsf)3]2[H2bpp]2 and [U4O10(dbsf)3][H2bpp], have been hydrothermally synthesized from a semi-rigid carboxylic acid, H2dbsf, with the organic base, bpp, as the charge balancing agent and stacking template (H2dbsf = 4,4'-dicarboxybiphenyl sulfone, bpp = 1,3-di(4-pyridyl)propane).

NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

BACKGROUND: Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. METHODS: Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. RESULTS: Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. CONCLUSION: Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage.

The first case of actinide triple helices: pH-dependent structural evolution and kinetically-controlled transformation of two supramolecular conformational isomers.

The first actinide triple helices, including two supramolecular conformational isomers of uranium(VI), have been synthesized with the aid of a flexible V-shaped ligand and a rigid aromatic base. The isomers exhibit an intriguing pH-dependent structural evolution and a kinetically-controlled transformation via a novel conformational rearrangement of the organic base.

Utility of uric acid as a risk marker of extubation success in chronic obstructive pulmonary disease.

BACKGROUND: The objective of this observational study was to determine whether there is an association between extubation success and uric acid in chronic obstructive pulmonary disease patients with mechanical ventilation admitted to the intensive care units, and identify the risk markers for extubation success in COPD patients with mechanical ventilation. METHODS: Consecutive COPD patients with intubation were screened at baseline. The study included patients on mechanical ventilation (MV) for over 12 hours and who, in the process of weaning, were subjected to low-level pressure support. Exclusion criteria were age under 18 years, ventilation via tracheotomy, and patients failing to cooperate for different reasons. The final study population consisted of 106 patients. Demographic, clinical, laboratory, and mechanical ventilation parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid on admission, duration of mechanical ventilation, pressure support ventilation, and APACHE II score on admission were significantly higher in COPD patients with extubation failure than in those with extubation success (p < 0.05), but lower tidal volume before weaning was observed in COPD patients with extubation failure. Among these patients, multiple logistic analyses indicated the independent risk factors for extubation success in the COPD subjects included serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. The diagnosis analysis showed that higher uric acid level and APACHE II score on admission and longer duration of mechanical ventilation had a significant ability to reflect extubation success in the COPD patients with respiratory failure. CONCLUSIONS: The novel finding of this study is that the extubation failure in COPD patients with respiratory failure is strongly related to serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. These results might be helpful for selecting the best time to remove the tracheal intubation and improving extubation success rate in COPD patients with respiratory failure.

Risk factors for postoperative delirium in patients after coronary artery bypass grafting: A prospective cohort study.

PURPOSE: This study was designed to identify the incidence and independent perioperative risk factors associated with postoperative delirium of patients who underwent coronary artery bypass grafting (CABG) in a large intensive care unit setting in China. METHODS: Delirium was diagnosed by the confusion assessment method for the intensive care unit (CAM-ICU). Baseline demographics, perioperative data, and postoperative outcomes of 249 consecutive patients who underwent CABG were recorded prospectively and analyzed via univariate analysis and multivariate logistic regression to determine the independent risk factors of postoperative delirium. RESULTS: Postoperative delirium was detected in 76 patients according to CAM-ICU criteria. The incidence was 30.52%. Patients with and without delirium differed significantly on 34 variables (P < .05). Multivariate logistic regression analysis revealed that preoperative atrial fibrillation (odds ratio [OR], 3.957; 95% confidence interval [CI], 1.727-9.066), elevated European system for cardiac operative risk evaluation (OR, 1.178; 95% CI, 1.018-1.364), cognitive impairment (OR, 3.231; 95% CI, 1.008-10.356), prolonged surgery duration (OR, 1.008; 95% CI, 1.003-1.014), postoperative poor quality of sleep (OR, 5.001; 95% CI, 2.476-10.101), and electrolyte disturbance (OR, 2.095; 95% CI, 1.041-4.216) were independently associated with postoperative delirium after CABG. CONCLUSIONS: Delirium is a frequent complication. Factors independently associated with delirium are preoperative atrial fibrillation, elevated European system for cardiac operative risk evaluation and cognitive impairment, longer surgery duration, postoperative poor quality of sleep, and electrolyte disturbance. The study may be helpful in decreasing the incidence of postoperative delirium after CABG by treating these predictors properly.

Azithromycin attenuates pulmonary inflammation and emphysema in smoking-induced COPD model in rats.

INTRODUCTION: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed. RESULTS: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. CONCLUSIONS: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres (¹³¹I-GMSs) following intratumoral injection.

INTRODUCTION: The aim of this study was to investigate the effects of 131I gelatin microspheres (131I-GMS) on human breast cancer cells (MCF-7) in nude mice and the biodistribution of 131I-GMSs following intratumoral injections. METHODS: A total of 20 tumor-bearing mice were divided into a treatment group and control group and received intratumoral injections of 2.5 mci 131I-GMSs and nonradioactive GMSs, respectively. Tumor size was measured once per week. Another 16 mice received intratumoral injections of 0.4 mci 131I-GMSs and were subjected to single photon emission computed tomography (SPECT) scans and tissue radioactivity concentration measurements on day 1, 4, 8 and 16 postinjection. The 20 tumor-bearing mice received intratumoral injections of 0.4 mci [131I] sodium iodide solution and were subjected to SPECT scans and intratumoral radioactivity measurements at 1, 6, 24, 48 and 72 h postinjection. The tumors were collected for histological examination. RESULTS: The average tumor volume in the 131I-GMSs group on post-treatment day 21 decreased to 86.82 ± 63.6%, while it increased to 893.37 ± 158.12% in the control group (P < 0.01 vs. the 131I-GMSs group). 131I-GMSs provided much higher intratumoral retention of radioactivity, resulting in 19.93 ± 5.24% of the injected radioactivity after 16 days, whereas the control group retained only 1.83 ± 0.46% of the injected radioactivity within the tumors at 1 h postinjection. CONCLUSIONS: 131I-GMSs suppressed the growth of MCF-7 in nude mice and provided sustained intratumoral radioactivity retention. The results suggest the potential of 131I-GMSs for clinical applications in radiotherapy for breast cancer.

Effect of (131)I gelatin microspheres on hepatocellular carcinoma in nude mice and its distribution after intratumoral injection.

In this study, we investigated the effect of (131)I gelatin microspheres ((131)I-GMSs) on human hepatocellular carcinoma cells (HepG2) in nude mice (Balb/c) and the biodistribution of (131)I-GMSs after intratumoral injection. The treatment group and control group animals received intratumoral injections of 1 mCi (131)I-GMSs and GMSs unlabeled (131)I, respectively. The size of the implanted tumor was measured once a week for 8 weeks, and the survival time was calculated from the day of injection to 64 days post-injection. Another 35 animals received intratumoral injections of 0.2 mCi (131)I-GMSs and were subject to single-photon emission computed tomography (SPECT) on days 1, 8, 16, 24 and 32 post-injection. Samples of various organs were collected and used to calculate tissue concentrations on days 1, 4, 8, 16 and 24. Free thyroxine (FT4) in fetal bovine serum was tested to evaluate thyroid function. The tumors were collected for histological examination. (131)I-GMSs produced a pronounced reduction in HepG2 tumor volume, and the overall survival was 73.3% in the treatment group and only 13.3% in the control group (P < 0.001). Tissue radioactivity concentration measurements and SPECT demonstrated that the injected (131)I-GMSs mainly accumulated within the tumors. The concentration of FT4 was stable during the observation period. The microspheres could be observed by histological methods on day 32. (131)I-GMSs suppressed the growth of HepG2 in the nude mice and were retained in the tumor for a long period of time after injection. Direct intratumoral injection of (131)I-GMSs offers a promising modality for the treatment of hepatocellular carcinoma.

Uric acid levels in obstructive sleep apnea patients with atrial fibrillation.

BACKGROUND AND AIMS: The objective of this observational study was to determine whether there is an association between atrial fibrillation (AF) and uric acid and to identify the risk markers for AF in obstructive sleep apnea (OSA). METHODS: Consecutive patients with newly diagnosed OSA were screened at baseline. The final study population consisted of 516 patients. One hundred and eight patients had AF. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid, triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial diameter, interventricular septum thickness, apnea hypopnea index, and Epworth sleepiness scale were significantly higher in OSA patients with AF than in those without AF (p <0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for AF occurrence in the OSA subjects included serum uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP. The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter and percentage of time with SaO2 <90% had a significant ability to reflect the presence of AF occurrence. CONCLUSIONS: The novel finding of this study is that the occurrence of AF in OSA patients is strongly related to serum uric acid level, left atrial diameter, percentage of time with SaO2 <90% and CRP level. These results may be helpful for monitoring AF occurrence in OSA patients.