Regarding radioactive iodine-refractory failure or advanced differentiated thyroid cancer,multiple multikinase inhibitors including sorafenib and lenvatinib,which target platelet derived growth factor receptor,vascular endothelial growth factor pathway,and rearranged during transfection (RET) pathway were proved to have obvious antitumor activity.Moreover,selective BRAF inhibitor,promoting drug uptake of radioactive iodine also showed a certain therapeutic effect.These molecular targets which are relevant with differentiated thyroid cancer occurrence,development,invasion and metastasis have become of its moment,and,selective inhibitors and re-differentiation agents were shown to be promising.In the future,individual genetic testing would provide more specific information in directing individualized molecular-targeted therapy.

[Objective] To observe the effect of Allergic Rhinitis Oral Liquid (AROL) on perennial allergic rhinitis (PAR) and to explore its therapeutic mechanism. AROL, composed of modified Guizhi Tang and Yupingfeng San, has the actions of strengthening spleen and lung, replenishing Qi and consolidating superficies and dispelling pathogens and dredging orifices. [Methods] One hundred and twenty-nine cases of confirmed PAR were randomized into Group A (n=43), Group B (n=43) and Group C (n=43). Group A was treated with AROL, Group B with Biyankang Tablets and Group C with normal saline. Three groups were treated for 4 weeks as one treatment course, and another treatment course was carried out one week after interval. Therapeutic effect were observed after treatment and serum levels of interleukin-4 (IL-4) and specific IgE antibody were detected. [Results] The total effective rate was 93.02% in Group A (P

Objective:To improve the Rapid Arterial Occlusion Evaluation (RACE) scale and to investigate its value in identifying large vessel occlusion (LVO) in patients with acute anterior circulation ischemic stroke (AIS).Methods:Consecutive patients with AIS treated in Liangxiang Hospital of Fangshan District, Beijing through stroke easy access from January 1, 2016 to December 31, 2018 were enrolled prospectively. The clinical data and multimodal CT examinations required to determine LVO were collected. The existing problems in the RACE score were modified. The patients were evaluated by the modified RACE score, RACE score, and National Institute of Health Stroke Scale (NIHSS). The receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the modified RACE score for LVO, and it was compared with the RACE score and NIHSS score. The ROC curves of LVO predicted by modified RACE score and NIHSS score in patients with left and right hemispheric lesions were compared.Results:A total of 184 patients were included, of which 66 (35.9%) had LVO. The age (64.8±11.7 vs. 60.5±10.8 years; t=2.483, P=0.014), baseline NIHSS score (13 [6.75-17] vs. 5 [2-9]; Z=-6.361, P<0.001) and the proportion of patients with gaze (37.9% vs. 17.4%; χ2=4.696, P=0.030) in the LVO group were significantly higher than those in the non-LVO group. ROC curve showed that the modified RACE score was more effective in identifying LVO than RACE score (area under the curve: 0.812 vs. 0.770; Z=4.654, P<0.001). The best cutoff value of the modified RACE score in predicting LVO was 5, and its predictive sensitivity and specificity were 75.8% and 75.4%, respectively, and the positive and negative predictive values were 63.3% and 84.8%, respectively. A comparison of patients with left hemispheric lesion and those with right hemispheric lesion showed that the ability of the modified RACE score in predicting LVO was more balanced (area under the curve: 0.826 vs. 0.796; Z=0.454, P=0.650), while there was a significant difference in NIHSS score (area under the curve: 0.856 vs. 0.703; Z=2.149, P=0.031). Conclusions:The modified RACE score is better than the original RACE score in the predictive value of LVO in patients with AIS, and its predictive power of LVO in patients with left and right hemisphere stroke is more balanced than the NIHSS score, which may help clinical discrimination and screening for patients suitable endovascular treatment.

Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.
Amino Acid Motifs ; Amino Acid Substitution ; Base Composition ; Codon ; genetics ; Computational Biology ; DNA Mutational Analysis ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Variation ; Genome, Viral ; Phylogeny ; SARS Virus ; genetics

Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.
Amino Acid Substitution ; Base Composition ; Base Sequence ; Computational Biology ; methods ; Genome, Viral ; Isoelectric Point ; Models, Genetic ; Molecular Sequence Data ; Molecular Weight ; Open Reading Frames ; SARS Virus ; genetics ; Sequence Analysis ; Transcription, Genetic

The R (replicase) protein is the uniquely defined non-structural protein (NSP) responsible for RNA replication, mutation rate or fidelity, regulation of transcription in coronaviruses and many other ssRNA viruses. Based on our complete genome sequences of four isolates (BJ01-BJ04) of SARS-CoV from Beijing, China, we analyzed the structure and predicted functions of the R protein in comparison with 13 other isolates of SARS-CoV and 6 other coronaviruses. The entire ORF (open-reading frame) encodes for two major enzyme activities, RNA-dependent RNA polymerase (RdRp) and proteinase activities. The R polyprotein undergoes a complex proteolytic process to produce 15 function-related peptides. A hydrophobic domain (HOD) and a hydrophilic domain (HID) are newly identified within NSP1. The substitution rate of the R protein is close to the average of the SARS-CoV genome. The functional domains in all NSPs of the R protein give different phylogenetic results that suggest their different mutation rate under selective pressure. Eleven highly conserved regions in RdRp and twelve cleavage sites by 3CLP (chymotrypsin-like protein) have been identified as potential drug targets. Findings suggest that it is possible to obtain information about the phylogeny of SARS-CoV, as well as potential tools for drug design, genotyping and diagnostics of SARS.
Amino Acid Sequence ; Base Composition ; Base Sequence ; Cluster Analysis ; Computational Biology ; Conserved Sequence ; genetics ; Evolution, Molecular ; Gene Components ; Genome, Viral ; Molecular Sequence Data ; Mutation ; genetics ; Phylogeny ; Protein Structure, Tertiary ; RNA Replicase ; genetics ; SARS Virus ; genetics ; Sequence Analysis, DNA

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city's hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.
Genome, Viral ; Haplotypes ; Humans ; Mutation ; Open Reading Frames ; Phylogeny ; SARS Virus ; genetics