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A straightforward and novel controllable site-selective construction of 2- and 4-substituted pyrimido[1,2-b]indazole from 3-aminoindazoles and ynals has been developed. The high regioselectivity of this reaction could be easily switched by converting different catalytic systems. In this way, a series of 2- and 4-substituted pyrimido[1,2-b]indazole derivatives were obtained in moderate to good yields. In addition, the photophysical properties of compound 3a prepared by the present method were discussed.

Background To explore the clinical value of energy spectrum curves of dual-energy computer tomography (CT) in quantitative evaluation of different pathological grades of gastric adenocarcinoma. Methods A total of 62 patients with 36 poorly, 25 moderately and 1 well differentiated gastric adenocarcinomas confirmed pathologically were collected. Dual-energy CT plain and enhanced scanning were undergone before operation. Dual-Energy software was used to measure the slope of the energy spectrum curves (λ) in arterial and venous phases (VPs) after image reconstruction. Patients were divided into two groups according to the pathological results, including well and moderately differentiated gastric adenocarcinoma group and poorly differentiated gastric adenocarcinoma group. Data of each group were analyzed by independent sample t-test. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficiency of the corresponding parameters. Results There were significant differences in λ values of 40–50, 40–60, 40–80, 40–90, 40–100, 40–120, 40–130, 40–140 and 40–150 keV energy ranges in VP between the well and moderately differentiated group and poorly differentiated group (P0.05). And the area under curve in 40–120 keV energy range was the largest in VP. λ40–120keV=2.69 was selected as the diagnostic threshold with the maximum Youden index, the sensitivity and specificity were 61.1% and 76%, respectively. Conclusions The energy spectrum curve of dual-energy CT had certain diagnostic value in the quantitative evaluation of pathological grading of gastric adenocarcinoma.

A straightforward and novel controllable site-selective construction of 2- and 4-substituted pyrimido[1,2

Coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to medical education systems and medical students. The aim of this study was to investigate the effects of COVID-19 pandemic on medical career and specialty choices among medical students. An online cross-sectional survey of Chinese medical students was conducted during the COVID-19 pandemic from February to April 2020. The students’ willingness to be a doctor before and after the COVID-19 pandemic and changed willingness to specialize in respiratory medicine and infectious diseases were investigated. Multiple linear regression and binary logistic regression was used to explore factors that were associated with changes of willingness. A total of 1,837 medical students, including 1,227 females (66.8%), with a median age of 21.0 years, were recruited. Of the participants, 10.6% and 6.9% showed increased and decreased willingness to be a doctor after the COVID-19 outbreak, respectively. Moreover, 11.7% showed increased willingness and 9.5% showed decreased willingness to major in respiratory medicine and infectious diseases. Students with younger age, lower household income, fewer depressive symptoms, less exposure to negative pandemic information and more satisfaction with their own major after the pandemic were associated with increased willingness to be a doctor. Students who engaged in regular exercise, were males and undergraduate level, were interested in medicine, paid more attention to positive information, were satisfied with their majors, and had increased willingness to be a doctor after the pandemic were more likely to choose to specialize in respiratory medicine and infectious disease. However, the severity of anxiety symptoms was associated with decreased willingness to work in the specialties of respiratory medicine and infectious diseases. Psychological problems and professional satisfaction appear to be independent factors that affect medial career and specialty choices. The impacts of the COVID-19 pandemic on medical students require further research.

The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA cycle are associated with IDH1 mut. Here, we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism, and the TCA cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate, and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine, and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA-cycle activity in IDH1 mut gliomas.

Backgroud: Accurate diagnosis of cancer staging and pathological differentiation are critical for the formulation of individualized treatment and prognosis of gastric cancer. It is vital to explore non-invasive preoperative imaging techniques to evaluate the pathological differentiation degree of gastric cancer tissues, and provide better diagnostic basis and decision-making reference for treatment. The purpose of this study was to explore the clinical value of energy spectrum curves of dual-source dual-energy CT in the quantitative evaluation of different pathological grades of gastric adenocarcinoma. Methods: A total of 62 patients with 1 well, 25 moderately and 36 poorly differentiated gastric adenocarcinomas pathologically confirmed by surgery were collected, and they underwent dual-source dual-energy CT plain scanning and enhanced scanning before operation. Dual-Energy software was used to measure the slope of the energy spectrum curves (λ) in arterial and venous phases after image reconstruction. Patients were divided into two groups according to the pathological results, including well and moderately differentiated gastric adenocarcinoma group and poorly differentiated gastric adenocarcinoma group. Data of each group were analyzed by independent sample t-test. The receiver operating characteristic curve was plotted to evaluate the diagnostic efficiency of the corresponding parameters. Results: There were significant differences in λ values of 40-50keV, 40-60keV, 40-80keV, 40-90keV, 40-100keV, 40-120keV, 40-130keV, 40-140keV and 40-150keV energy ranges in venous phase between the well and moderately differentiated group and poorly differentiated group (P0.05). And the area under curve in 40-120keV energy range was the largest in venous phase. K40-120keV =2.69 was selected as the diagnostic threshold with the maximum Youden index, the sensitivity and specificity were 61.1% and 76%, respectively. Conclusion: The energy spectrum curve of dual-energy CT had certain diagnostic value in the quantitative evaluation of pathological grading of gastric adenocarcinoma.

The present study aimed to identify microRNAs (miRNAs) involved in regulating retinal neovascularization and retinopathy of prematurity (ROP). A total of 80 healthy C57BL/6 neonatal mice were randomly divided into the oxygen-induced retinopathy (OIR) group (n=40), in which 7-day-old mice were maintained in 75% oxygen conditions for 5 days, or the control group (n=40). Following collection of retinal tissue, retinal angiography and hematoxylin and eosin (H&E) staining were performed. Total RNA was also extracted from retinal tissue, and miRNA microarrays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to identify differentially expressed miRNAs in the two groups. Retinal angiography and H&E staining revealed damage to retinas in the OIR group. Compared with the control group, 67 miRNAs were differentially expressed in the OIR group, of which 34 were upregulated and 33 were downregulated. Of these differentially expressed miRNAs, 32 exhibited a fold change ≥2, of which 21 were upregulated and 11 were downregulated. The results of RT-qPCR for miR-130a-3p and miR-5107-5p were in accordance with those of the miRNA microarray. The newly identified miRNAs may be important in the development of ROP, and may provide a basis for future research into the mechanisms of ROP.

The first Enterovirus 71 (EV71) strain isolated in 1969 was classified as genotype A. It is interesting that the genotype A disappeared nearly 40 years until its re-emergence in mainland China in 2008-2010. Few studies on genetic characterization of the re-emerged genotype A viruses have been reported. In this study, a series of analyses were performed on molecular epidemiology and genome recombination of genotype A viruses in China. Phylogenetic analysis indicated that except for 17 reported genotype A strains and 3 orphan strains (C0, C3 and B5), almost all EV71 strains in mainland China were belonging to subgenotype C4 during 1987-2011. The subgenotype C4 was further divided into 3 clades C4a1, C4a2, and C4b. The genotype A viruses co-circulated with the predominant clade C4a2 and the re-emerged clade C4b both in eastern and central China in 2008-2009. Moreover, comprehensive recombination analysis showed that the genotype A viruses were "triple-recombinant" by combination of intratypic and intertypic recombination. Intertypic recombination between the oldest C4b strain (SHZH98) and Coxsackievirus A5 (CVA5) and intratypic recombination between the SHZH98 and C1 strains both with one junction in 5'-UTR were observed for some specific C4a2 strains and the re-emerged C4b strain, respectively. And intratypic recombination between the re-emerged C4b strain and the specific C4a2 strains with one junction in 5'-UTR was observed for the Chinese genotype A viruses. Taken together, these results provided potential explanations for the genesis of Chinese genotype A viruses which were significant for preventing and controlling outbreaks.

Enterovirus 71 (EV71) is a neurotropic virus that causes various clinical manifestations in young children, ranging from asymptomatic to fatal. Different pathotypes of EV71 notably differ in virulence. Several virulence determinants of EV71 have been predicted. However, these reported virulence determinants could not be used to identify the EV71 strains of subgenotype C4, which mainly circulate in China. In this study, VP1 sequences of 37 EV71 strains from severe cases (SC-EV71) and 192 EV71 strains from mild cases (MC-EV71) in mainland China were analyzed to determine the potential virulence determinants in the capsid protein VP1 of EV71. Although most SC-EV71 strains belonged to subgenotype C4a, no specific genetic lineages in C4a were correlated with EV71 virulence. Interestingly, amino acid substitutions at nine positions (H22Q, P27S, N31S/D, E98K, E145G/Q, D164E, T240A/S, V249I, and A289T) were detected by aligning the VP1 sequences of the SC-EV71 and MC-EV71 strains. Moreover, both the constituent ratios of the conservative or mutated residues in the MC-EV71 and SC-EV71 strains and the changes in the VP1 3D structure resulting from these mutations confirmed that the conservative residues (22H, 249V, and 289A) and the mutated residues (27S, 31S/D, 98K, 145G/Q, 164E, and 240A/S) might be potential virulence determinants in VP1 of EV71. Furthermore, these results led to the hypothesis that VP1 acts as a sandwich switch for viral particle stabilization and cellular receptors attachment, and specific mutations in this protein can convert mild cases into severe cases. These findings highlight new opportunities for diagnostic and therapeutic interventions.

Aqueous oxidation treatment of COD and color in landfill leachate with the combination of hydrogen peroxide and ferrous ion, Fenton reagent, has been studied. The effect of variables such as concentration of both reactants and pH has been investigated. Best concentrations seem to be 0.6 and 3.0 mol/L for H2O2 and Fe2+ ion, respectively. The other important variable, pH of landfill leachate should be near 7. From the experimental results can be known the determined process was the generation of hydroxyl radicals involving in advanced oxidation. Oxidation rates are even higher than those of other advanced oxidation systems involving ozone, UV radiation, and hydrogen peroxide.