tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children.

BACKGROUND: With the exploding prevalence of obesity, many children are at risk of developing nonalcoholic fatty liver disease. Using anthropometric and laboratory parameters, our study aimed to develop a model to quantitatively evaluate liver fat content (LFC) in children with obesity. METHODS: A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort. The external validation cohort comprised 77 children. The assessment of liver fat content was performed using proton magnetic resonance spectroscopy. Anthropometry and laboratory metrics were measured in all subjects. B-ultrasound examination was carried out in the external validation cohort. The Kruskal-Wallis test, Spearman bivariate correlation analyses, univariable linear regressions and multivariable linear regression were used to build the optimal predictive model. RESULTS: The model was based on indicators including alanine aminotransferase, homeostasis model assessment of insulin resistance, triglycerides, waist circumference and Tanner stage. The adjusted R2 of the model was 0.589, which presented high sensitivity and specificity both in internal [sensitivity of 0.824, specificity of 0.900, area under curve (AUC) of 0.900 with a 95% confidence interval: 0.783-1.000] and external validation (sensitivity of 0.918 and specificity of 0.821, AUC of 0.901 with a 95% confidence interval: 0.818-0.984). CONCLUSIONS: Our model based on five clinical indicators was simple, non-invasive, and inexpensive; it had high sensitivity and specificity in predicting LFC in children. Thus, it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study.

OBJECTIVE: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Phylogenetically and catabolically diverse diazotrophs reside in deep-sea cold seep sediments.

Microbially mediated nitrogen cycling in carbon-dominated cold seep environments remains poorly understood. So far anaerobic methanotrophic archaea (ANME-2) and their sulfate-reducing bacterial partners (SEEP-SRB1 clade) have been identified as diazotrophs in deep sea cold seep sediments. However, it is unclear whether other microbial groups can perform nitrogen fixation in such ecosystems. To fill this gap, we analyzed 61 metagenomes, 1428 metagenome-assembled genomes, and six metatranscriptomes derived from 11 globally distributed cold seeps. These sediments contain phylogenetically diverse nitrogenase genes corresponding to an expanded diversity of diazotrophic lineages. Diverse catabolic pathways were predicted to provide ATP for nitrogen fixation, suggesting diazotrophy in cold seeps is not necessarily associated with sulfate-dependent anaerobic oxidation of methane. Nitrogen fixation genes among various diazotrophic groups in cold seeps were inferred to be genetically mobile and subject to purifying selection. Our findings extend the capacity for diazotrophy to five candidate phyla (Altarchaeia, Omnitrophota, FCPU426, Caldatribacteriota and UBA6262), and suggest that cold seep diazotrophs might contribute substantially to the global nitrogen balance.

Feasibility of balanced steady-state free precession sequence at 1.5T for the evaluation of hepatic steatosis in obese children and adolescents.

OBJECTIVES: To determine the feasibility of balanced steady-state free precession (b-SSFP) imaging for measuring hepatic steatosis in obese children and adolescents, using proton magnetic resonance spectroscopy (1H MRS) as reference standard. METHODS: 182 obese Chinese paediatric patients underwent conventional T1-weighted dual echo MRI, 1H MRS and b-SSFP imaging for non-invasive assessment of hepatic steatosis. RESULTS: There was a strong positive correlation between liver fat fraction (FF) on T1-weighted dual echo MRI and 1H MRS-determined liver fat content (LFC) (r = 0.964, p < .001), and a strong negative correlation between the ratio of liver signal intensity (SI) to spleen SI (L/S) on b-SSFP and LFC (r = -0.896, p < .001). ROC curve analysis based on a diagnostic threshold of 1H MRS-determined LFC >50 mg/g (>5 % by wet weight) showed areas under the curves for FF and L/S at 0.989 (0.976-1.000) and 0.926 (0.888-0.964), respectively. Optimal FF and L/S cut-off values identified patients with hepatic steatosis with 97.9 % and 86.5 % sensitivity and 93.4 % and 93.4 % specificity, respectively. CONCLUSIONS: Following further validation, b-SSFP at 1.5T has potential as a feasible technique for evaluation of hepatic steatosis in obese paediatric patients with limited breath-holding capacity. KEY POINTS: • L/S on b-SSFP images closely correlated with 1 H MRS-determined LFC. • b-SSFP has high diagnostic accuracy for hepatic steatosis in obese children. • 100% of obese paediatric subjects are imaged successfully using b-SSFP sequence. • b-SSFP has potential to evaluate hepatic steatosis in children with poor breath-hold.

Fluoride Induces Neuroinflammation and Alters Wnt Signaling Pathway in BV2 Microglial Cells.

Fluoride is a common element in nature and our daily life, and excessive intake of this element can cause fluorosis and irreversible brain damage. The toxic effects of fluoride on the central nervous system may be attributed to the release of inflammatory cytokines and ROS. GSK3ß is a key protein that modulates NF-κB activity and inflammatory cytokine levels and plays an important role in the Wnt signaling pathway. In this study, we found that fluoride altered the inflammatory status and oxidative stress by inhibiting Wnt signaling pathway activity. This study thus provides a valid basis for the fluorine-induced neuroinflammation injury theory.

[Diagnostic value of ultrasonographic examination for hepatic steatosis in obese children].

OBJECTIVE: To evaluate the sensitivity and specificity of hepatic ultrasonography (US) for the diagnosis of hepatic steatosis in obese children, using ¹H magnetic resonance spectroscopy (¹H MRS) as the reference standard. METHODS: A total of 162 obese children with age of 10.5 ± 2.2 years and BMI of 28 ± 4 were enrolled in this study. They accepted hepatic US and (1)H MRS examinations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US were calculated for the overall presence of hepatic steatosis by comparison with ¹H MRS results. RESULTS: Using quantitative criteria of liver fat content (LFC) >5% determined by (1)H MRS, 95 children(58.6%)were diagnosed as having hepatic steatosis. The sensitivity and specificity of US in diagnosing steatosis were 91.6% (87/95) and 50.7% (34/67) respectively, with PPV of 72.5% (87/120), and NPV of 81.0% (34/42). Considerable overlap in LFC measured by ¹H MRS was observed between different grades from US findings: absent (LFC interquartile range: 1.3%-3.9%), mild (2.4%-10.7%), moderate (7.1%-20.2%) and severe (7.6%-28.8%) steatosis. CONCLUSIONS: The US can yield a high sensitivity and low specificity in the diagnosis of hepatic steatosis in obese children, suggesting it can be used as a screening tool for hepatic steatosis. To improve diagnostics, ¹H MRS is needed to determine LFC.

Quantitative evaluation of the axonal degeneration of central motor neurons in chronic cerebral stroke with diffusion tensor imaging.

BACKGROUND: Conventional magnetic resonance imaging (MRI) can only show the degeneration-induced morphological changes but fail to quantitatively reveal the degree and extent of the axonal damage of nerve fibers. Diffusion tensor imaging (DTI) has the ability to detect the diffusion of water molecules and thus suitable to the study of axonal degeneration of central motor neurons. PURPOSE: To illustrate and quantitatively evaluate the axonal degeneration of central motor neurons in patients with chronic cerebral stroke. MATERIAL AND METHODS: DTI and conventional MRI were carried out with 10 normal control subjects and 25 patients who suffered from chronic cerebral stroke in the region supplied by middle cerebral artery and had varying degrees of limb movement disorders (the mean time of onset was 2.5 months), to measure the fractional anisotropy (FA), volume ratio (VR), apparent diffusion coefficient (ADC), tensor eigenvalues (λ1, λ2, and λ3), and signal intensity (SI) on T2-weighted images, of the central motor fibers (pyramidal tract) in the plane of cerebral peduncle. Results from the ipsilateral side were compared with those from the contralateral side in the same patient and with those from normal control. RESULTS: The axonal degeneration of central motor neurons manifests in DTI as the decline of FA of the pyramidal tract and the reduction and distortion of the high signal area. While all the FA, VR, ADC, and λ1 in the ipsilateral side reduce on DTI, λ3 increases; the T2-weighted signals exhibit no significant differences among groups. CONCLUSION: The changes and diffusions of water molecule associated with the axonal degeneration of central motor neurons after chronic cerebral stroke can be detected by DTI, which can directly quantitatively reflect the degree and extent of axonal degeneration of central motor neurons and can compensate the shortcomings of conventional MRI and diffusion-weighted imaging (DWI).

Comparison of magnetic resonance enterography, capsule endoscopy and gastrointestinal radiography of children with small bowel Crohn's disease.

The aim of this study was to compare magnetic resonance enterography (MRE) findings with those of video capsule endoscopy (VCE) or conventional gastrointestinal radiography (CGR) in pediatric patients with small bowel Crohn's disease. A total of 55 cases of small bowel Crohn's disease that were diagnosed through clinical, laboratory, surgical and histopathological findings were reviewed. Prior to the examination, children suspected of having other types of diseases of the small intestinal were identified. The pulse sequences included coronal T2-true-fast imaging with steady-state precession (TrueFISP) images, navigation axial and coronal T1-weighted images, T2-weighted fat-suppressed images and coronal fat-suppressed three-dimensional gradient-echo images, immediately followed by contrast-enhanced axial and coronal T1-weighted fat-suppressed images. Findings from MRE were compared with those of VCE (n=39) and CGR (n=37). MRE results exhibited a number of features characteristic to small bowel Crohn's disease, including wall thickening, mesenteric fibrofatty changes and mesenteric vasculature changes. VCE, MRE and CGR demonstrated sensitivities of 94.6, 85.7 and 71.1% with specificities of 72.7, 70 and 40%; accuracies of 89.6, 82.2 and 61.1%; positive predictive values of 92.1, 90.9 and 59.6%; and negative predictive values of 80, 58.3 and 40%, respectively. VCE depicted mucosal pathologies missed by MRE in three patients. MRE revealed 83 extraenteric findings in 55 patients and CGR was able to show the dynamic evolution of the gastrointestinal function. MRE is a simple, safe, non-invasive and effective method for evaluating small bowel Crohn's disease. VCE allows visualization and readily characterizes subtle mucosal lesions missed by MRE, whereas MRE yields additional mural, perienteric and extraenteric information. However, oral barium CGR utilizes radiation, which is not suitable for repeated use in children.

Biomechanical analysis of the acetabular buttress-plate: are complex acetabular fractures in the quadrilateral area stable after treatment with anterior construct plate-1/3 tube buttress plate fixation?

OBJECTIVE: The acetabular buttress-plate has been widely used in treating difficult cases with satisfying clinical results. However, the biomechanical properties of a postoperative acetabular fracture fixed by the buttress-plate are not clear. The purpose of this study was to evaluate the biomechanical properties of stability after the anterior tube buttress-plate fixation of complex acetabular fractures in the quadrilateral area. METHODS: A construct was proposed based on anterior construct plate - 1/3 tube buttress plate fixation for acetabular both-column fractures. Two groups of six formalin-preserved cadaveric pelvises were analyzed: (1) group A, the normal pelvis and (2) group B, anterior construct plate-1/3 tube buttress plate with quadrilateral area fixation. The displacements were measured, and cyclical loads were applied in both standing and sitting simulations. RESULTS: As the load was added, the displacements were A

Biomechanical analysis of the acetabular buttress-plate: are complex acetabular fractures in the quadrilateral area stable after treatment with anterior construct plate-1/3 tube buttress plate fixation?

OBJECTIVE: The acetabular buttress-plate has been widely used in treating difficult cases with satisfying clinical results. However, the biomechanical properties of a postoperative acetabular fracture fixed by the buttress-plate are not clear. The purpose of this study was to evaluate the biomechanical properties of stability after the anterior tube buttress-plate fixation of complex acetabular fractures in the quadrilateral area. METHODS: A construct was proposed based on anterior construct plate - 1/3 tube buttress plate fixation for acetabular both-column fractures. Two groups of six formalin-preserved cadaveric pelvises were analyzed: (1) group A, the normal pelvis and (2) group B, anterior construct plate-1/3 tube buttress plate with quadrilateral area fixation. The displacements were measured, and cyclical loads were applied in both standing and sitting simulations. RESULTS: As the load was added, the displacements were A<B, increasing in line. In the 600 N physiological loading, the differences were significant (standing position: p = 0.013; sitting position: p = 0.009) between groups A and B. CONCLUSION: The anterior construct plate - 1/3 tube buttress plate fixation provided a better stable construct for early sitting. The standing mode yielded more significant differences between the groups. Placing a 1/3 tube buttress-plate via an anterior approach is a novel method of providing quadrilateral area support in this setting. .

Enhanced desulfurizing flotation of coal using sonoelectrochemical method.

Enhanced desulfurizing flotation of low sulfur coal was investigated using sonoelectrochemical method. The supporting electrolyte used in this process was sodium chloride and the additive was anhydrous ethanol. The effects of treatment conditions on desulfurization were studied by a single-factor method. The conditions include anhydrous ethanol concentration, sodium chloride concentration, sonoelectrolytic voltage, sonoelectrolytic temperature, sonoelectrolytic time and coal sample granulometry. The optimal experimental conditions achieved for anhydrous ethanol concentration, sodium chloride concentration, sonoelectrolytic voltage, sonoelectrolytic temperature and sonoelectrolytic time are 1.7 mol L(-1), 5.1×10(-3) mol L(-1), 10 V, 70 °C, 50 min achieved for a -0.18 mm coal sample. Optimal conditions cause a sulfur reduction of up to 69.4%. The raw and treated coals were analyzed by infrared spectroscopy and a chemical method. Pyritic sulfur, organic sulfur, ash as well as moisture are partially removed. The combination of high sulfur reduction, high yield, as well as high ash reduction was obtained in the newly developed method of enhanced flotation by sonoelectrochemistry. Ultrasound irradiation promotes electron transfer efficiency and increases clean coal yield.

Household solid fuel use and pulmonary function in an urban population in Shanghai, China.

OBJECTIVES: We examined the association between household solid fuel exposure and lung function in a densely populated district in urban Shanghai, China. METHODS: Spirometry was performed in 12 506 subjects, aged 18 and over, residing in the Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid fuel use at home was assessed by an administered questionnaire, estimating duration and total amount of solid fuel use at home during the lifetime. RESULTS: After adjusting for confounders, the subjects with exposure to household solid fuel had a 1.3% (95% CI 0.57 to 2.02) decrease in forced expiratory volume in 1 s (FEV(1)) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced vital capacity (FVC) percent predicted, respectively. Trends towards decreased pulmonary function measures were seen for longer duration and greater amount of household fuel use at home, in the highest compared with lowest tertile (p values for trend <0.001). We observed decrease in FEV(1) and FVC percent predicted across increase in tertile of body mass index in association with in-home solid fuel exposure. CONCLUSIONS: This study suggests that in-home solid fuel exposure is associated with reduced lung function in an urban population.

[Quantitative assessment of intrahepatic fat content in children and adolescents with non-alcoholic fatty liver disease].

OBJECTIVE: To quantitatively evaluate clinical significance of intrahepatic fat (IHF) content in children and adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS: Ninety-three obese children were enrolled in this study. Physical parameters, liver function, serum lipids, glycemic and insulin related parameters were measured. Liver B-mode ultrasound (US) examination was performed. IHF content was quantified by 1H magnetic resonance spectroscopy (1H MRS). Three subgroups were classified according to the conditional diagnostic criteria for obese children: simple obesity (n=31), NAFLD-1 (US fatty liver and normal alanine aminotransterase, n=33) and NAFLD-2 (US fatty liver and elevated alanine aminotransterase, n=29). Twenty healthy age- and sex-matched children served as a control group. IHF content among the four groups was compared. The relationship of IHF content with other common clinical laboratory parameters and independent factors influencing increased IHF content were investigated. RESULTS: IHF content measured by 1H MRS was 0.80% (0.4%-1.0%), 2.9% (1.7%-4.30%), 14.0% (7.2%-17.5%) and 18.8% (14.0%-29.1%) respectively in the control, simple obese, NAFLD-1 and NAFLD-2 groups. There were significant differences in IHF content between the groups. Univariate correlation analysis demonstrated that IHF content was positively correlated with waist circumference, hip circumference, waisttohip ratio, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminoreansferase, γ-glutamic acid transtetase, triglyceride, low-density lipoprotein, OGTT 2-hour plasma glucose, fasting insulin, 2-hour insulin and insulin resisfence, and negatively correlated with high-density lipoprotein. Multivariate linear regression analysis demonstrated three independent risk factors for increased IHF content: increased waist circumference, increased 2-hour plasma glucose and decreased high-density lipoprotein levels. CONCLUSIONS: IHF content determined by 1H MRS can reflect early hepatic fatty infiltration and is closely related to the occurrence and progress of NAFLD in obese children and adolescents. There is a significant correlation between most of common clinical laboratory parameters and IHF content, and waist circumference, high-density lipoprotein and OGTT 2-hour plasma glucose are independent factors impacting IHF content.

Effect of leptin on bone metabolism in rat model of traumatic brain injury and femoral fracture.

OBJECTIVE: To observe serum and callus leptin expression within the setting of fracture and traumatic brain injury (TBI). METHODS: A total of 64 male SD rats were randomized equally into 4 groups: nonoperated group, TBI group, fracture group, and fracture+TBI group. Rats were sacrificed at 2, 4, 8 and 12 weeks after fracture+TBI. Serum leptin was detected using radioimmunoassay, and callus formation was measured radiologically. Callus leptin was analyzed by immunohistochemistry. RESULTS: Serum leptin levels in the fracture group, TBI group and combined fracture+TBI group were all significantly increased compared with control group at the 2 week time-point (P less than 0.05). Serum leptin in the combined fracture +TBI group was significantly higher than that in the fracture and TBI groups at 4 and 8 weeks after injury (P less than 0.05). The percentage of leptin-positive cells in the fracture+TBI callus and callus volume were significantly higher than those in the fracture-only group (P less than 0.01). CONCLUSIONS: We demonstrated elevated leptin expression within healing bone especially in the first 8 weeks in a rat model of fracture and TBI. A close association exists between leptin levels and the degree of callus formation in fractures.

Imaging features of pediatric pentastomiasis infection: a case report.

We report here a case of pentastomiasis infection in a 3-year-old girl who had high fever, abdominal pain, abdominal tension and anemia. Ultrasound scanning of the abdomen revealed disseminated hyperechoic nodules in the liver and a small amount of ascites. Abdominal MRI showed marked hepatomegaly with disseminated miliary nodules of high signal intensity throughout the hepatic parenchyma on T2-weighted images; retroperitoneal lymphadenopathy and disseminated miliary nodules on the peritoneum were also noted. Chest CT showed scattered small hyperdense nodules on both sides of the lungs. The laparoscopy demonstrated diffuse white nodules on the liver surface and the peritoneum. After the small intestinal wall and peritoneal biopsy, histological examination revealed parenchymal tubercles containing several larvae of pentastomids and a large amount of inflammatory cell infiltration around them. The pathological diagnosis was parasitic granuloma from pentastomiasis infection.

Long-term effects of work cessation on respiratory health of textile workers: a 25-year follow-up study.

RATIONALE: The degree to which chronic respiratory health effects caused by exposures to cotton dust and endotoxin is reversible after cessation of textile work is unknown. OBJECTIVES: To investigate changes in lung function and respiratory symptoms after cessation of textile work and to determine whether past exposure to cotton dust and endotoxin or smoking history modify the associations. METHODS: We performed a prospective cohort study consisting of 447 cotton textile workers exposed to cotton dust and 472 unexposed silk textile workers, with a 25-year follow-up. Spirometry testing and respiratory questionnaires were conducted at 5-year intervals. Generalized estimated equations were used to model the average 5-year change in FEV(1) and odds ratios of respiratory symptom prevalence. MEASUREMENTS AND MAIN RESULTS: Years since cessation of textile work was positively associated with 11.3 ml/yr and 5.6 ml/yr gains in 5-year FEV(1) change for cotton and silk workers, respectively. Among male cotton workers, smokers gained more FEV(1) per year after cessation of exposure than did nonsmokers, and the risk of symptoms of chronic bronchitis and byssinosis was larger for smoking than for nonsmoking male cotton workers. CONCLUSIONS: Cessation of textile work was significantly associated with improvement in lung function and respiratory symptoms. The positive effect of work cessation was greater for cotton workers than for silk workers. For cotton workers, the improvement in lung function loss after cessation of textile work was greater among smokers, but no differences were observed for silk workers.