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Qin Wang,* Chenggui Liu,* Jian Xu, Peipei Song, Shuzhe Yang, Qin Zhang Department of Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin WangDepartment of Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 1617, Riyue Avenue, Qingyang District, Chengdu, 611731, People’s Republic of ChinaTel +86 28 61866000-6267Email 314306221@qq.comObjective: In order to fight against coronavirus disease 2019 (COVID-19) better and to share our experience as a reference for clinical laboratory departments.Methods: This was a retrospective study conducted in the clinical laboratory department of Chengdu Women’s and Children’s Central Hospital in Chengdu, China, from April 2020 to January 2021. The number of nucleic acid and antibody testing specimens of suspected COVID-19 cases was analyzed. The key points of suspected-case sample processing and detection in the clinical laboratory department were summarized. The laboratory was directly involved in the sample processing and testing of suspected cases, the release of reports, and the transfer of specimens to the fever clinic.Results: The number of COVID-19 nucleic acid test specimens in our laboratory ranged from 102 to 2170 per day, and the number of antibody test specimens ranged from 24 to 391 per day. There were four main considerations in the treatment and detection of suspected-case specimens in the clinical laboratory: biosafety management in clinical laboratory departments, measures to ensure the health of the staff, the eight time points for processing suspected-case samples (turn-around time), and key points for the detection of suspected case specimens.Conclusion: The laboratory developed a protective process for COVID-19 antibody and nucleic acid detection during the pandemic. At present, the detection of COVID-19 antibodies and nucleic acids in the clinical laboratory department is orderly, and there have been no cases of laboratory infection.Keywords: COVID-19, clinical laboratory, laboratory tests

Previous studies have indicated the important role of block of proliferation 1 (BOP1) in the progression of several malignant tumors; no comprehensive pan-cancer analysis of BOP1 has been performed. Here, we aim to systematically identify the expression, prognostic value, and potential immunological functions of BOP1 in 33 malignancies. We obtained the gene expression data and clinical information from multiple public databases to assess the expression level and prognostic value of BOP1 in 33 cancers. We also analyzed the relationship between BOP1 expression and DNA methylation, tumor microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoints. Moreover, we conducted gene set enrichment analysis (GSEA) to investigate the biological function and signal transduction pathways of BOP1 in different types of tumors. Finally, we validated the expression of BOP1 in lung cancer cell line and detected the influence of BOP1 on lung cancer cell migration and the expression of epithelial-mesenchymal transition- (EMT-) related genes. Collectively, our findings elucidated that BOP1 has the potential to be a promising molecular prognostic biomarker for predicting poor survival in various malignant tumors, as well as a cancer-promoting gene involved in tumorigenesis and tumor immunity.

Background: Efforts to precisely assess tumor-specific T-cell immune responses capable of mediating imbalanced hepatocellular carcinoma (HCC) ecosystems after incomplete radiofrequency ablation (iRFA) still face major challenges. Here, we assessed the immune response and performed transcriptomic and proteomic analyses in patients with HCC following iRFA. Methods: Peripheral blood and tissue samples were collected from HCC patients who underwent RFA. Multiplex immunostaining and flow cytometry were used to assess the local and systemic immune response. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. The ability of proteinase-3 (PRTN3) to predict overall survival (OS) was assessed in HCC patients with early recurrence after RFA. Results: Multiplex immunostaining revealed no immediate significant change in local immune cell counts. Flow cytometry analysis showed that the levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Treg cells were significantly increased, while the levels of CD16+CD56+ natural killer cells were significantly decreased on day 5 after cRFA (PConclusion: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of HCC milieus, revealing the mechanisms involved in the iRFA-induced immune response and tumor progression. Trial registration: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588.

Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor-­kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein–protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.

Highlights • Dysregulated and excessive cytokine storm is essential for critically ill COVID-19 development. • Mechanisms of SARS-CoV-2-infected included ACE2 receptor-mediated inflammatory response, Cell Pyroptosis, Delayed IFN-α and -β response, and Anti-S-IgG-mediated inflammatory response. • Infected lung epithelial cells and macrophages mainly release cytokines involved in innate immunity and adaptive immunity. • Endothelial cells damage and microvascular thrombosis played an important role in pathophysiological changes of COVID-19 involved respiratory failure, hypotension, liver and kidney injury. • Individualized targeted cytokine drug therapy might an effective measure to alleviate the violent inflammation besides Remdesivir, Chloroquine, Lopinavir and Ritonavir, Favipiravir etc., A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.

RNA binding proteins (RBPs) dysregulation have been reported in various malignant tumors and associated with the occurrence and development of cancer. However, the role of RBPs in lung adenocarcinoma (LUAD) is poorly understood. We downloaded the RNA sequencing data of LUAD from the Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. The study then systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis. A total of 223 differently expressed RBPs were identified, including 101 up-regulated and 122 down-regulated RBPs. Eight RBPs (IGF2BP1, IFIT1B, PABPC1, TLR8, GAPDH, PIWIL4, RNPC3, and ZC3H12C) were identified as prognosis related hub gene and used to construct a prognostic model. Further analysis indicated that the patients in the high-risk subgroup had poor overall survival(OS) compared to those in low-risk subgroup based on the model. The area under the curve of the time-dependent receiver operator characteristic curve of the prognostic model are 0.775 in TCGA cohort and 0.814 in GSE31210 cohort, confirming a good prognostic model. We also established a nomogram based on eight RBPs mRNA and internal validation in the TCGA cohort, which displayed a favorable discriminating ability for lung adenocarcinoma.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment.Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls.Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively.Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR2100046954.

Background: Haemophilus influenzae is an opportunistic pathogen of the human respiratory tract. Haemophilus influenzae can cause not only respiratory tract infection in children but also otitis media, epiglottitis and sinusitis. With the widespread use of antibiotics, the positive rate of β-lactamase in H. influenzae is increasing, and the rate of antimicrobial resistance is also increasing, which increases the difficulty of clinical treatment. Objectives: To study the infection characteristics of patients and the antibiotic resistance of H. influenzae in lower respiratory tract samples of children in Chengdu, so as to provide a reference for its clinical diagnosis and the rational use of antibiotics. Methods: Sputum samples of 15891 children aged 0-14 years with lower respiratory tract infection were collected. Haemophilus influenzae was cultured and identified, its drug susceptibility tested, and the results determined according to the guidelines of CLSI 2020. Results: A total of 15891 clinical isolate strains in sputum were detected for drug sensitivity from December 2018 to January 2020, of which 5488 were H. influenzae, accounting for 34.54% (5488/15891). The sex of children infected with H. influenzae was not skewed (P > 0.05). The detection rate of H. influenzae was the highest in children aged 7 - 11 months, and the lowest was in the age group ≤ 28 d. The detection rate was the highest in spring and the lowest in autumn. The positive rate of β-lactamase was 92.0%, the resistance rate to ampicillin was 92.0%, the sensitivity to amoxicillin/clavulanate was 70.2%, and the sensitivity to cefotaxime, ofloxacin, tetracycline, chloramphenicol, and rifampicin was more than 90.0%. Conclusions: Children aged 7 months to 14 years were generally susceptible to H. influenzae in spring, and the positive rate of β-lactamase was high. Doctors should refer to the infection characteristics and drug resistance of H. influenzae and choose antibiotics correctly to better control the infection.

Background As the mechanism of systemic inflammatory response in the course of cancer progression is gradually revealed, research has begun to focus on the two indictors of neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) which may be associated with clinical disease development, treatment, and prognosis in patients who are undergoing surgery, chemotherapy, targeted therapy, and immunotherapy. We aim to define the clinical application values of those two biomarkers in multiple cancers. Methods PubMed and Web of Science are used to perform the systematic literature research. Related articles and references were identified for analyzing the association of between NLR and PLR with treatment outcome, as well as progression of cancers. Results NLR and PLR are convenient, easy to calculate, economical, and practical biomarkers, effectively predicting treatment outcome and risk of death based on inflammatory cells. Elevated NLR and PLR are significantly in line with worse clinical pathological characteristics, deeper invasiveness, more lymph node metastasis and advanced TNM stage. A significant association was observed that high NLR and PLR predict poor overall survival and disease-free survival. Conclusions NLR and PLR can be used as available biomarkers in prognostic survival and formulation of treatment strategy of multiple cancers.

RNA binding proteins (RBPs) dysregulation have been reported in various malignant tumors and associated with the occurrence and development of cancer. However, the role of RBPs in lung adenocarcinoma (LUAD) is poorly understood. We downloaded the RNA sequencing data of LUAD from the Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. The study then systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis. A total of 223 differently expressed RBPs were identified, including 101 up-regulated and 122 down-regulated RBPs. Eight RBPs (IGF2BP1, IFIT1B, PABPC1, TLR8, GAPDH, PIWIL4, RNPC3, and ZC3H12C) were identified as prognosis related hub gene and used to construct a prognostic model. Further analysis indicated that the patients in the high-risk subgroup had poor overall survival(OS) compared to those in low-risk subgroup based on the model. The area under the curve of the time-dependent receiver operator characteristic curve of the prognostic model are 0.775 in TCGA cohort and 0.814 in GSE31210 cohort, confirming a good prognostic model. We also established a nomogram based on eight RBPs mRNA and internal validation in the TCGA cohort, which displayed a favorable discriminating ability for lung adenocarcinoma.

Diethyl phthalate (DEP) is a plastic additive that entered the soil environment due to the extensive use of plastic products. However, its toxicity to soil animals and the associated toxicity mechanism were not completely understood.