Clinical characteristics of 15 patients with listeria meningitis in adult.

Objective: To report and analyze the clinical characteristics of 15 patients with Listeria meningitis in adult. Methods: We reviewed the medical records of 15 patients with Listeria meningitis who were admitted to Shanxi Bethune Hospital between January 2017 and January 2023. Results: The clinical manifestations was primarily characterized by fever， altered mental status, headache, neck stiffness, and vomiting. Blood or cerebrospinal fluid (CSF) cultures were performed in 15 cases, and pathogens were detected in 11 of them. Metagenomic next-generation sequencing (mNGS) detected pathogens in 10 cases, with four being negative by conventional methods and six being positive through traditional tests. The laboratory blood results presented leukocytosis. The CSF analysis upon admission showed elevated levels of white blood cells and proteins, as well as decreased chloride and glucose concentration. The brain computed tomography (CT) revealed ventricular enlargement in 3 patients. The brain magnetic resonance imaging (MRI) showed abnormalities in multiple areas of the brain. Despite 3 patients with decompensated hydrocephalus underwent lateral ventricle puncture and drainage，their neurological deterioration were increasingly deteriorating.7 patients were treated by mechanical ventilation due to respiratory insufficiency. After 3 months, there were 9 cases with excellent outcomes（modified Rankin Scale score of 0-2）,2 cases with favorable outcomes（score of 3-5）, and 4 deaths（score of 6）. Conclusions: This thesis found that the detection rate of Listeria monocytogenes has been on a rise over the past six years in our department, ranking second only to Streptococcus pneumoniae. Additionally, the detection rate achieved by mNGS surpasses that of other conventional methods. Among the patient cohort, 11 had underlying diseases such as systemic lupus erythematosus, tuberculosis, diabetes mellitus, pituitary neoplasms, leukemia and other related illnesses. Once listeriosis is early identified, the adequate antibiotic therapy should be promptly introduced in the course of empirical treatment.

Integrated analysis of single-cell and bulk RNA-seq establishes a novel signature for prediction in gastric cancer.

BACKGROUND: Single-cell sequencing technology provides the capability to analyze changes in specific cell types during the progression of disease. However, previous single-cell sequencing studies on gastric cancer (GC) have largely focused on immune cells and stromal cells, and further elucidation is required regarding the alterations that occur in gastric epithelial cells during the development of GC. AIM: To create a GC prediction model based on single-cell and bulk RNA sequencing (bulk RNA-seq) data. METHODS: In this study, we conducted a comprehensive analysis by integrating three single-cell RNA sequencing (scRNA-seq) datasets and ten bulk RNA-seq datasets. Our analysis mainly focused on determining cell proportions and identifying differentially expressed genes (DEGs). Specifically, we performed differential expression analysis among epithelial cells in GC tissues and normal gastric tissues (NAGs) and utilized both single-cell and bulk RNA-seq data to establish a prediction model for GC. We further validated the accuracy of the GC prediction model in bulk RNA-seq data. We also used Kaplan-Meier plots to verify the correlation between genes in the prediction model and the prognosis of GC. RESULTS: By analyzing scRNA-seq data from a total of 70707 cells from GC tissue, NAG, and chronic gastric tissue, 10 cell types were identified, and DEGs in GC and normal epithelial cells were screened. After determining the DEGs in GC and normal gastric samples identified by bulk RNA-seq data, a GC predictive classifier was constructed using the Least absolute shrinkage and selection operator (LASSO) and random forest methods. The LASSO classifier showed good performance in both validation and model verification using The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) datasets [area under the curve (AUC)_min = 0.988, AUC_1se = 0.994], and the random forest model also achieved good results with the validation set (AUC = 0.92). Genes TIMP1, PLOD3, CKS2, TYMP, TNFRSF10B, CPNE1, GDF15, BCAP31, and CLDN7 were identified to have high importance values in multiple GC predictive models, and KM-PLOTTER analysis showed their relevance to GC prognosis, suggesting their potential for use in GC diagnosis and treatment. CONCLUSION: A predictive classifier was established based on the analysis of RNA-seq data, and the genes in it are expected to serve as auxiliary markers in the clinical diagnosis of GC.

Comparison of single­nucleus and single­cell transcriptomes in hepatocellular carcinoma tissue.

Single­nucleus RNA sequencing (snRNA­seq) is a method used to analyze gene expression in cells for which isolation is complex, such as those in hepatocellular carcinoma (HCC) tissues. It constitutes an alternative to single­cell RNA sequencing (scRNA­seq) by analyzing the nucleus rather than the whole cell; however, whether it can completely replace scRNA­seq in HCC remains to be clarified. In the present study, scRNA­seq was compared with snRNA­seq in tumor tissue obtained from patients with HCC, using the 10X Genomics Chromium platform. Seurat was also used to process the data and compare the differences between the two sequencing methods in identifying different cell types. In the present study, the transcriptomes of 14,349 single nuclei and 9,504 single cells were obtained from the aforementioned HCC tissue. A total of 21 discrete cell clusters, including hepatocytes, endothelial cells, fibroblasts, B cells, T cells, natural killer cells and macrophages were identified. Notably, a high number of hepatocytes were detected using snRNA­seq, while an increased number of immunocytes were identified in the tumor microenvironment using scRNA­seq. Results of the present study provided a comprehensive image of human HCC at a single­cell resolution. Moreover, results of the present study further demonstrated that snRNA­seq may be adequate in replacing scRNA­seq in certain cases, and snRNA­seq performs at an improved level in hepatocyte sequencing. Combined use of the two sequencing methods may contribute to the study of intercellular interactions.

Incidence rates, risk factors, and outcomes of aspiration pneumonia after gastric endoscopic submucosal dissection: A systematic review and meta-analysis.

BACKGROUND AND AIM: The risk and prognosis of aspiration pneumonia (AP) after endoscopic submucosal dissection (ESD) are inconsistent among studies. We aim to estimate the incidence, risk factors, and outcome of AP in patients after gastric ESD. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Knowledge were searched for relevant articles from inception until April 2020. Data involving the incidence, risk factors, and outcomes were extracted. Pooled incidence, odds ratios (ORs), or standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated. RESULTS: Forty records involving 48 674 subjects were finally included. The pooled incidence of AP after gastric ESD was 1.9% (95% CI, 1.2-2.7) via the double arcsine transformation method and 1.6% (1.1-2.5%) via the logit transformation method. Risk factors analyses revealed that old age (OR, 2.52; 95% CI, 1.99-3.18), comorbid pulmonary disease (2.49; 1.66-3.74), comorbid cerebrovascular disease (2.68; 1.05-6.85), remnant stomach (4.91; 1.83-13.14), sedation with propofol (2.51; 1.48-4.28), and long procedural duration (count data: 5.20, 1.25-21.7; measurement data: 1.01, 1.01-1.02) were related to the occurrence of AP. Patients with AP had a longer hospital stay (SMD, 0.56; 95% CI, 0.25-0.87) than those without AP. CONCLUSIONS: About 1.9% (1.2-2.7%) of the patients who receive gastric ESD may develop AP, resulting in prolonged hospital stay. More attention should be paid in patients who are older; have comorbidities such as pulmonary diseases, cerebrovascular diseases, or gastric remnant; or require a long procedural duration or deep sedation with propofol.

Toward Candidate Proteomic Biomarkers in Clinical Monitoring of Acute Promyelocytic Leukemia Treatment with Arsenic Trioxide.

The introduction of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) has resulted in high clinical complete remission (CR) rates over 90%. On the contrary, the risk for early death (ED) in APL patients treated with ATO continues to have a negative impact for optimization of APL therapeutics. There is an urgent need for precision medicine and biomarkers in clinical monitoring of ATO toxicity in APL, and ED in particular. This retrospective case series cohort proteomics study was conducted as a hypothesis generation effort and provides here several potential molecular leads on serum peptides expressed at different times after treatment with ATO in patients with APL. In 12 patients with a de novo APL diagnosis, and treated with single-agent ATO as frontline remission induction therapy, serum peptides were fractionated by weak cation exchange magnetic beads and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Ten peptides (m/z 2075.5, 2084.2, 2203.0, 2265.2, 2872.8, 2916.6, 3145.2, 3153.4, 3953.4, and 3964.8) were significantly downregulated in serum after ATO treatment. Among them, four peptides were identified as (1) Immunoglobulin heavy chain V-III region BUT, (2) RRP15-like protein, (3) filaggrin, and (4) protein SON isoform F. To the best of our knowledge, this is the first clinical oncology proteomic biomarker study with a view to future rational therapeutic monitoring of patients with APL in the course of single-agent ATO treatment and hematological CR.

C1QTNF6 is overexpressed in gastric carcinoma and contributes to the proliferation and migration of gastric carcinoma cells.

In the present study, proteins differentially expressed between gastric cancer tissue and para­tumoral normal gastric tissues were screened, and the function of the highly expressed protein C1QTNF6 in gastric carcinoma was investigated. The differential expression of mRNAs extracted from the tumor and adjacent tissues was analyzed using GeneChip assay. An AGS si­C1QTNF6 cell line was constructed using shRNA­C1QTNF6 lentivirus. The cell invasion and migration ability of C1QTNF6­knockdown cells were determined by Transwell chamber migration and wound healing assays, respectively. The effects of C1QTNF6 on AGS cell cycle distribution and apoptosis were detected using a FACScan flow cytometer. The results demonstrated that the expression of 109 genes was increased and the expression of 129 was decreased in tumor tissues. Among these genes, the C1QTNF6 gene was highly expressed in tumor tissues and the AGS7901 cell line. C1QTNF6­knockdown decreased the cell growth, and the proliferative and migration ability, as well as increasing the apoptosis of gastric carcinoma cells. In addition, the number of AGS cells in the G2/M phase was significantly increased after 5 days of C1QTNF6­shRNA lentivirus infection. The results of the present study indicated that C1QTNF6 serves an important role in the development of gastric carcinoma. C1QTNF6 is involved in promoting the proliferation and migration, and in reducing the apoptosis of gastric carcinoma cells. These results provided a potential therapeutic target for the treatment of gastric carcinoma.

Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts.

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.

Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21-1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application.

Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND: The clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. To investigate this question, we conducted a meta-analysis. METHODS: A comprehensive literature search of electronic databases (up to July 10, 2016) was performed for relevant studies using multiple search strategies. Correlation between PD-L1 expression and clinicopathological features/overall survival (OS) was analyzed. RESULTS: A total of 1,350 ESCC patients from eight studies were included. The pooled odds ratios (ORs) indicated that none of the clinicopathological characteristics was correlated with PD-L1 expression, including gender [OR =0.84; 95% confidence interval (CI): 0.59-1.18; P=0.31], histological differentiation (OR =1.33; 95% CI: 0.95-1.85; P=0.09), tumor depth (OR =0.66; 95% CI: 0.33-1.35; P=0.26), status of lymph node metastasis (OR =0.67; 95% CI: 0.30-1.52; P=0.34), distal metastasis (OR =0.66; 95% CI: 0.40-1.09; P=0.10) and tumor node metastasis (TNM) stage (OR =0.93; 95% CI: 0.49-1.75; P=0.82). The combined hazard ratio (HR) for OS showed a trend that overexpression of PD-L1 might be associated with the survival outcome of ESCC, though the difference was not statistically significant (HR =1.65; 95% CI 0.95-2.85; P=0.07). CONCLUSIONS: Based on the published studies, PD-L1 overexpression in ESCC was not associated with common clinicopathological characteristics. PD-L1 might be a poor prognostic biomarker for ESCC. Further large-scale research should be performed to reveal the precise clinicopathological and prognostic significance of PD-L1 in ESCC by unified testing standard.

Identification and differential expression of human carcinoma-associated antigens in hepatocellular carcinoma tissues.

This study was designed to identify and verify hepatocellular carcinoma (HCC)-associated human carcinoma antigens (HCAs) that may be useful as tumor markers for HCC. We found that BCE075 and BCD021 anti-HCA antibodies were immunostained in the liver tissue samples and showed specific staining. Their expression was increased in HCC compared with normal liver tissues (P = 0.008). Immunoprecipitation and mass spectrometry analyses of the proteins precipitated by these two antibodies were identified to be cytoskeleton-associated protein 4 (CLIMP63) and brain-type glycogen phosphorylase (PYGB). This study demonstrated that HCC tissues expressed specific HCA glycoproteins, suggesting that our mouse monoclonal anti-HCA antibodies could be useful for immunohistochemical analysis of HCA expression as potential biomarkers for HCC diagnosis.