Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Background and Aims:Kaempferol is a natural flavonoid compound that can regulate various processes and activities associated with cancer,such as the cell cycle,oxidative stress,apoptosis,proliferation,metastasis,and angiogenesis. Its potential for treating breast cancer has been validated in some studies,but its mechanism of action remains unclear. Therefore,this study was conducted to explore the potential targets and pathways of kaempferol in the treatment of breast cancer and establish a prognostic model.Methods:Using network pharmacology and bioinformatics approaches,the intersection targets of kaempferol for the treatment of breast cancer were obtained from databases such as HERB,GeneCards,STRING,PubChem,RCSB PDB,and TCGA. Protein interaction,GO analysis,and KEGG pathway enrichment analysis were performed,followed by molecular docking for validation. Prognostic-related genes were identified through LASSO-Cox regression analysis to establish a risk score model. The prognostic analysis for each gene,and the correlation between risk score and immune infiltration were analyzed. Results:Network pharmacology analysis identified 55 intersection targets. Protein interaction analysis revealed five potential key genes (Akt1,Bcl2,CASP3,ESR1,AR). GO analysis showed that kaempferol treatment of breast cancer involved 1604 biological process entries,20 cellular component entries,and 121 molecular function entries. KEGG pathway enrichment mainly included pathways related to chemical carcinogenesis,reactive oxygen species signaling,AGE-RAGE signaling in diabetic complications,TNF signaling,and IL-17 signaling. Molecular docking results indicated that kaempferol had a strong affinity for key targets,with the best binding effect observed with ESR1 (-9.1 kcal/mol). Ten prognostic genes (Bcl2,CYP1B1,DPP4,GSTM1,GSTM2,MMP1,NCOA2,NOS2,NR1I3,PTGS2) were obtained through LASSO-Cox regression analysis,and a risk score model was established. The AUC of this model for predicting breast cancer patient prognosis was greater than 0.5. Single-gene survival analysis indicated that higher expression of Bcl2 (HR=0.61,95％ CI=0.43-0.86,P=0.005),CYP1B1 (HR=0.68,95％ CI=0.49-0.94,P=0.022),GSTM1 (HR=0.68,95％ CI=0.47-0.98,P=0.037),GSTM2 (HR=0.64,95％ CI=0.46-0.90,P=0.010),and PTGS2 (HR=0.62,95％ CI=0.44-0.86,P=0.005) correlated with a higher overall survival (OS),while higher expression of MMP1 (HR=1.72,95％ CI=1.22-2.41,P=0.002),NCOA2 (HR=1.71,95％ CI=1.12-2.60,P=0.013),NOS2 (HR=1.67,95％ CI=1.20-2.32,P=0.002),and NR1I3 (HR=1.69,95％ CI=1.21-2.37,P=0.002) was associated with worse OS. The risk score was negatively correlated with the infiltration of T cells,CD8+T cells,myeloid dendritic cells,NK cells,and B cells,and positively correlated with monocyte/macrophage infiltration (all P<0.05).Conclusion:Kaempferol exerts therapeutic effects on breast cancer through multiple targets and pathways. The prognostic genes identified based on its related targets,along with the established prognostic model,can guide clinical treatment of breast cancer. The correlation between the prognostic model and immune infiltration provides direction for future experimental studies.

Background and Aims:Kaempferol is a natural flavonoid compound that can regulate various processes and activities associated with cancer,such as the cell cycle,oxidative stress,apoptosis,proliferation,metastasis,and angiogenesis. Its potential for treating breast cancer has been validated in some studies,but its mechanism of action remains unclear. Therefore,this study was conducted to explore the potential targets and pathways of kaempferol in the treatment of breast cancer and establish a prognostic model.Methods:Using network pharmacology and bioinformatics approaches,the intersection targets of kaempferol for the treatment of breast cancer were obtained from databases such as HERB,GeneCards,STRING,PubChem,RCSB PDB,and TCGA. Protein interaction,GO analysis,and KEGG pathway enrichment analysis were performed,followed by molecular docking for validation. Prognostic-related genes were identified through LASSO-Cox regression analysis to establish a risk score model. The prognostic analysis for each gene,and the correlation between risk score and immune infiltration were analyzed. Results:Network pharmacology analysis identified 55 intersection targets. Protein interaction analysis revealed five potential key genes (Akt1,Bcl2,CASP3,ESR1,AR). GO analysis showed that kaempferol treatment of breast cancer involved 1604 biological process entries,20 cellular component entries,and 121 molecular function entries. KEGG pathway enrichment mainly included pathways related to chemical carcinogenesis,reactive oxygen species signaling,AGE-RAGE signaling in diabetic complications,TNF signaling,and IL-17 signaling. Molecular docking results indicated that kaempferol had a strong affinity for key targets,with the best binding effect observed with ESR1 (-9.1 kcal/mol). Ten prognostic genes (Bcl2,CYP1B1,DPP4,GSTM1,GSTM2,MMP1,NCOA2,NOS2,NR1I3,PTGS2) were obtained through LASSO-Cox regression analysis,and a risk score model was established. The AUC of this model for predicting breast cancer patient prognosis was greater than 0.5. Single-gene survival analysis indicated that higher expression of Bcl2 (HR=0.61,95％ CI=0.43-0.86,P=0.005),CYP1B1 (HR=0.68,95％ CI=0.49-0.94,P=0.022),GSTM1 (HR=0.68,95％ CI=0.47-0.98,P=0.037),GSTM2 (HR=0.64,95％ CI=0.46-0.90,P=0.010),and PTGS2 (HR=0.62,95％ CI=0.44-0.86,P=0.005) correlated with a higher overall survival (OS),while higher expression of MMP1 (HR=1.72,95％ CI=1.22-2.41,P=0.002),NCOA2 (HR=1.71,95％ CI=1.12-2.60,P=0.013),NOS2 (HR=1.67,95％ CI=1.20-2.32,P=0.002),and NR1I3 (HR=1.69,95％ CI=1.21-2.37,P=0.002) was associated with worse OS. The risk score was negatively correlated with the infiltration of T cells,CD8+T cells,myeloid dendritic cells,NK cells,and B cells,and positively correlated with monocyte/macrophage infiltration (all P<0.05).Conclusion:Kaempferol exerts therapeutic effects on breast cancer through multiple targets and pathways. The prognostic genes identified based on its related targets,along with the established prognostic model,can guide clinical treatment of breast cancer. The correlation between the prognostic model and immune infiltration provides direction for future experimental studies.

Objective:To construct standard strains representing the main epidemic clades of HIV-1 in China, amplify the virus strains, and establish a seed lot.Methods:Six isolates of HIV-1 virus were identified and analyzed in genotype and phenotype, according to " interpretation for the social organization of the Standard strains of pathogenic microorganism- technical specifications for establishment of HIV strains". The isolates were amplified and cultivated to generate the secondary generation primary seed lot and the third generation working seed lot as frozen storage in liquid nitrogen. Results:Six HIV-1 standard strains were obtained, of which 3 strains are CRF_ 07BC (NRPC2.4.9003, NRPC2.4.9005, NRPC2.4.9006), 1 strain is CRF_ 01AE (NRPC2.4.9001), 1 strain is CRF_ 08BC (NRPC2.4.9002), and 1 strain is URF (NRPC2.4.9004). Phenotypic detection showed that all six strains are CCR5 tropics and Non syncytia inducing virus. TCID 50 were all greater than 1 × 10 5/ml, and concentrations of p24 antigen were all higher than 2 ng/ml. A primary seed lot with no less than 20 vials per strain and a working seed lot with no less than 50 vials per strain were constructed. The standard virus strains were used in evaluating antiviral drugs PEG2kC34, PEG5kC34, LP-19, and neutralizing antibody LSEVh LS-F. Conclusions:Six standard strains of HIV-1 virus covering the three main epidemic subtypes of HIV-1 in China have been obtained, and a storage of HIV-1 standard strain was constructed. It meets the need of the preservation of HIV-1 standard strains in China and provides support for drug and vaccine evaluation.

Objective:To assess the significance of counting the number of caudal vertebral ossification centers (OCN) below fetal terminal conus medullaris in the screening for closed spina bifida and tethered cord syndrome (TCS).Methods:The OCN was counted in 961 normal fetuses(normal group) between 17 and 41 gestational weeks and in 140 fetuses with closed spina bifida or tethered cord syndrome(abnormal group) from Jan.2013 to Dec.2020 in Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Women and Children′s Hospital, School of Medicine, Xiamen University and Maternity and Child Health Care of Guangxi Zhuang Autonomous Region. The OCN was counted in the dorsal mid-sagittal section of fetal caudal spine.The reliability and agreement test were evaluated by intraclass correlation coefficients in another 50 normal fetuses. The OCN was compared between two groups. ROC curve and the cut-off value were constructed and calculated.Results:In normal group, the N increased with the growing of gestational age.In the subgroup of 17-20 weeks, the OCN ranged from 5 to 7 in most fetuses. In the others subgroups, the OCN was equal to or greater than 6 in 99.9% cases and more than 6 in 97.1% cases. In abnormal group, OCN was less than 7 in 93.0% fetuses and less than 6 in 82.8% cases. There were statistical differences between the two groups except for the subgroup of 17-20 gestational weeks( P<0.05). With the cut-off value of 6.5, the specificity and sensitivity were 93.0% and 94.3% respectively for predicting the presence of closed spinal dysraphism or TCS. Conclusions:OCN is a simple way to evaluate the position of conus medullaris and to screen for the skin-covered spine dysraphism or TSC. OCN is more than 6 in most normal fetuses. Further evaluation of spine is required in fetuses with N less than or equal to 6.

Objective: The purpose of this review of COVID-19 related research is to deepen our understanding of SARS-CoV-2, which would be inspire new ideas for targeted drug development and vaccine design, and further empower the prevention and control COVID-19. Methods: Through literature research and data analysis, we explored the process and mechanism of epitranscriptomics modification to regulate the replication and infectivity of COVID-19. Results: Provide important ideas and technical support for the prevention and control of SARS-CoV-2 infections and emerging epidemic diseases. Conclusions Taking the new research direction of epitranscriptomics as the starting point, it is expected to open up new scientific research concepts and paradigms.

At the end of 2019, COVID-19 broke out and spread rapidly in our country. Several kinds of emergency plans for epidemic prevention and control were consulted and prepared in Fifth Medical Center, PLA General Hospital. Some specialists in Department of Surgery and Operation Room also made surgery procedure, infection prevention and control measures for COVID-19 patients, including medical staff management and training, pre-surgical evaluation and preparation of patients, procedures for transferring patients, intraoperative nursing cooperation, disinfection of instruments and environmental objects after surgery. The above measures have been continuously revised in the clinical work.

Four-dimensional cone beam CT (4D-CBCT) imaging can provide accurate location information of real-time breathing for imaging-guided radiotherapy. How to improve the accuracy of 4D-CBCT reconstruction image is a hot topic in current studies. PICCS algorithm performs remarkably in all 4D-CBCT reconstruction algorithms based on CS theory. The improved PICCS algorithm proposed in this paper improves the prior image on the basis of the traditional PICCS algorithm. According to the location information of each phase, the corresponding prior image is constructed, which completely eliminates the motion blur of the reconstructed image caused by the mismatch of the projection data. Meanwhile, the data fidelity model of the proposed method is consistent with the traditional PICCS algorithm. The experimental results showed that the reconstructed image using the proposed method had a clearer organization boundary compared with that of images reconstructed using the traditional PICCS algorithm. This proposed method significantly reduced the motion artifact and improved the image resolution.
Algorithms ; Cone-Beam Computed Tomography ; methods ; Four-Dimensional Computed Tomography ; Humans ; Image Processing, Computer-Assisted ; Organ Motion ; Radiographic Image Enhancement ; instrumentation ; methods ; Respiration

BACKGROUND: Peanut allergy is an increasing problem in Singapore and strict avoidance is difficult as peanut is ubiquitous in Asian cuisine. OBJECTIVE: We aimed to assess the efficacy and safety of peanut oral immunotherapy (OIT) in children with obvious peanut allergy in Singapore. METHODS: This was an open-label study of peanut OIT in children living in Singapore, with 2 weekly dose escalation until final maintenance dose of 3,000 mg of peanut protein and a maintenance phase of 12 months. An oral food challenge was performed at 6 months to assess for desensitisation and at 4 weeks after discontinuation of OIT having completed 12 months of maintenance therapy to assess for possible sustained unresponsiveness. The adverse events were monitored using the symptom diaries. RESULTS: Nine subjects were started on OIT, with 7 managing to complete maintenance phase of therapy. Of these 7, all were able to tolerate at least 3,000 mg of peanut protein by 6 months of maintenance therapy, showing that the OIT was effective. Of these 7, 3 patients complied with the 4-week abstinence period after completion of OIT before another peanut challenge; 2 of the 3 subjects showed a significant decrease from the initial ability to tolerate 3,000 mg of peanut protein. Side effects were mainly gastrointestinal in nature and were more common during the updosing phase than the maintenance phase. No episodes of anaphylaxis were observed in this study. CONCLUSION: Peanut OIT seemed to be effective and safe in our cohort of Singaporean children.
Anaphylaxis ; Arachis ; Asian Continental Ancestry Group ; Child ; Cohort Studies ; Humans ; Hypersensitivity ; Immunotherapy ; Peanut Hypersensitivity ; Pilot Projects ; Probiotics ; Singapore