[Correlations of 18F-FDG PET/CT Metabolic Parameters and Metabolic Heterogeneity with Human Epidermal Growth Factor Receptor 2 Expression in Patients with Gastric Cancer].

Objective To investigate the value of 18F-FDG PET/CT metabolic parameters and metabolic heterogeneity for predicting the expression of human epidermal growth factor receptor 2 (HER2) in patients with gastric cancer. Methods A total of 45 patients with gastric cancer confirmed by surgical pathology between September 2016 and May 2021 were enrolled in this study.All the patients underwent 18F-FDG PET/CT examination before surgery.The maximum standardized uptake value (SUVmax),metabolic tumor volume (MTV),and total lesion glycolysis (TLG) of primary gastric cancer were measured,and the linear regression slope of MTV corresponding to different SUVmax thresholds (40% SUVmax and 80% SUVmax) was calculated.The absolute value of the slope was deemed to represent the metabolic heterogeneity of primary gastric cancer,termed the heterogeneity index (HI).Univariate and multivariate Logistic regression analyses were conducted to evaluate the correlations of 18F-FDG PET/CT metabolic parameters and HI with HER2 expression. Results The 45 patients included 10 with positive HER2 expression and 35 with negative result.The MTV (P=0.043) and HI (P=0.048) were lower in the patients with positive HER2 expression than in the patients with negative HER2 expression.The MTV and HI had the optimal thresholds of 12.10 cm3 and 3.71,respectively,which respectively showed the accuracy of 62.2% and 57.8% for predicting HER2 expression.The univariate Logistic regression showed that the tumor differentiation degree,MTV,and HI were correlated with HER2 expression,while the multivariate Logistic regression showed that only the tumor differentiation degree (OR=20.130,95%CI=1.843-219.860,P=0.014) was an independent predictor for HER2 expression.A further stratified analysis of the tumor differentiation degree showed that HER2 expression only varied among different MTV threshold groups in patients with moderately/well differentiated gastric cancer (P=0.031). Conclusions MTV and HI were associated with HER2 expression in gastric cancer,whereas neither played an independent predictive role.Therefore,these factors should be combined with clinicopathological characteristics of patients to jointly guide treatment decisions.

Precision Metagenomics: Rapid Metagenomic Analyses for Infectious Disease Diagnostics and Public Health Surveillance.

Next-generation sequencing (NGS) technologies have ushered in the era of precision medicine, transforming the way we treat cancer patients and diagnose disease. Concomitantly, the advent of these technologies has created a surge of microbiome and metagenomic studies over the last decade, many of which are focused on investigating the host-gene-microbial interactions responsible for the development and spread of infectious diseases, as well as delineating their key role in maintaining health. As we continue to discover more information about the etiology of infectious diseases, the translational potential of metagenomic NGS methods for treatment and rapid diagnosis is becoming abundantly clear. Here, we present a robust protocol for the implementation and application of "precision metagenomics" across various sequencing platforms for clinical samples. Such a pipeline integrates DNA/RNA extraction, library preparation, sequencing, and bioinformatics analyses for taxonomic classification, antimicrobial resistance (AMR) marker screening, and functional analysis (biochemical and metabolic pathway abundance). Moreover, the pipeline has 3 tracks: STAT for results within 24 h; Comprehensive that affords a more in-depth analysis and takes between 5 and 7 d, but offers antimicrobial resistance information; and Targeted, which also requires 5-7 d, but with more sensitive analysis for specific pathogens. Finally, we discuss the challenges that need to be addressed before full integration in the clinical setting.

BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9.

BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC). However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK) and human gingival fibroblasts (HGF). Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

Systemic Sclerosis is a Complex Disease Associated Mainly with Immune Regulatory and Inflammatory Genes.

Systemic sclerosis (SSc) is a fibrotic and autoimmune disease characterized clinically by skin and internal organ fibrosis and vascular damage, and serologically by the presence of circulating autoantibodies. Although etiopathogenesis is not yet well understood, the results of numerous genetic association studies support genetic contributions as an important factor to SSc. In this paper, the major genes of SSc are reviewed. The most recent genome-wide association studies (GWAS) are taken into account along with robust candidate gene studies. The literature search was performed on genetic association studies of SSc in PubMed between January 2000 and March 2014 while eligible studies generally had over 600 total participants with replication. A few genetic association studies with related functional changes in SSc patients were also included. A total of forty seven genes or specific genetic regions were reported to be associated with SSc, although some are controversial. These genes include HLA genes, STAT4, CD247, TBX21, PTPN22, TNFSF4, IL23R, IL2RA, IL-21, SCHIP1/IL12A, CD226, BANK1, C8orf13-BLK, PLD4, TLR-2, NLRP1, ATG5, IRF5, IRF8, TNFAIP3, IRAK1, NFKB1, TNIP1, FAS, MIF, HGF, OPN, IL-6, CXCL8, CCR6, CTGF, ITGAM, CAV1, MECP2, SOX5, JAZF1, DNASEIL3, XRCC1, XRCC4, PXK, CSK, GRB10, NOTCH4, RHOB, KIAA0319, PSD3 and PSOR1C1. These genes encode proteins mainly involved in immune regulation and inflammation, and some of them function in transcription, kinase activity, DNA cleavage and repair. The discovery of various SSc-associated genes is important in understanding the genetics of SSc and potential pathogenesis that contribute to the development of this disease.

Proton magnetic resonance spectroscopy in differentiating glioblastomas from primary cerebral lymphomas and brain metastases.

OBJECTIVE: To differentiate glioblastomas, primary cerebral lymphomas (PCLs), and brain metastases using multivoxel proton magnetic resonance (MR) spectroscopic imaging. METHODS: A total of 56 patients with brain neoplasms underwent MR imaging and proton MR spectroscopic imaging. The data were analyzed from contrast-enhancing and peritumoral regions (PTR). N-acetylaspartate/creatine (Cr), choline (Cho)/Cr, glutamate+glutamine/Cr, myo-inositol/Cr, and lipids+lactate/Cr ratios were computed, and pairwise comparisons between neoplasms were made using Mann-Whitney U tests. RESULTS: The PTR demonstrated most significant differences in metabolite ratios. The Cho/Cr ratio in glioblastomas (0.46 [0.01]) was significantly higher than that in metastases (0.38 [0.02], P = 0.01). Significantly elevated Cho/Cr levels were also noted in PCLs (0.48 [0.03]) compared with those in metastases (P = 0.04). In addition, PCLs also demonstrated significantly higher lipids+lactate/Cr levels (11.83 [2.59]) compared with glioblastomas (4.50 [0.59], P = 0.003) and metastases (2.79 [0.33], P = 0.001). CONCLUSIONS: Proton MR spectroscopic imaging from PTR may assist in the differentiation of glioblastomas, metastases, and PCLs.