The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval [CI], 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our metaanalysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

Pyroptosis, a newly discovered form of programmed cell death, is characterized by cell swelling, the protrusion of large bubbles from the plasma membrane and cell lysis. This death pathway is mediated by the pore formation of gasdermin D (GSDMD), which is activated by human caspase-1/caspase-4/caspase-5 (or mouse caspase-1/caspase11), and followed with the releasing of both cell contents and proinflammatory cytokines. Pyroptosis was initially found to function as an innate immune effector mechanism to facilitate host defense against pathogenic microorganisms, and subsequent studies revealed that pyroptosis also plays an eventful role in inflammatory immune diseases and tumor resistance. Recent studies have also shown that pyroptosis is involved in the initiation, the progression and complications of atherosclerosis. Here, we provide an overview of the role of pyroptosis in atherosclerosis by focusing on three important participating cells: ECs, macrophages, and SMCs. In addition, we also summarized drugs and stimuli that regulate the progression of atherosclerosis by influencing cell pyroptosis.

Background In this first national bloodstream infection (BSI) surveillance program in China, we assessed the composition of pathogenic bacteria and the trends for antimicrobial susceptibility over a 6-year period in China. Methods Blood bacterial isolates from patients at hospitals participating in the Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected from January 2014 to December 2019. Only the first isolate of a species per patient was eligible over the full study period. Antibiotic-susceptibility testing was conducted by agar-dilution or broth-dilution methods as recommended by the Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data. Results During the study period, 27,899 bacterial strains were collected. Gram-positive organisms accounted for 29.5% (8244) of the species identified and Gram-negative organisms accounted for 70.5% (19,655). The most-commonly isolated organisms in blood cultures were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, coagulase-negative Staphylococci, and Acinetobacter baumannii. The prevalence of multidrug-resistant organisms, such as E. coli, K. pneumoniae, A. baumannii was higher in tertiary hospitals, whereas extended-spectrum, β-lactamase-producing E. coli (ESBL-E. coli), carbapenem-resistant A. baumannii were more prevalent in economically-developing areas. The prevalence of methicillin-resistant S. aureus declined from 39.0% (73/187) in 2014 to 25.9% (230/889) in 2019 (p < 0.05). The prevalence of ESBL-E. coli dropped from 61.2% (412/673) to 51.0% (1878/3,683) over time (p < 0.05), and carbapenem-resistant E. coli remained low prevalence (< 2%; 145/9944; p = 0.397). In contrast, carbapenem-resistant K. pneumoniae increased markedly from 7.0% (16/229) in 2014 to 19.6% (325/1,655) in 2019 (p < 0.05). Conclusion E. coli and K. pneumoniae were the leading causes of BSI during the 6-year study period. The major resistant pathogens declined or remained stable, whereas carbapenem-resistant K. pneumoniae continued to increase, which poses a great therapeutic challenge for BSIs.

Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression.Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand (TYMSOS) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2ʹdeoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703. Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.gastric cancer (GC) has been ranked as the fifth most frequently occurred cancer and the third death cause related to cancers globally (Smyth et al., 2020). In terms of the risk factors, some found that racial and ethnic minorities, as well as smokers, face higher risks of GC (Kumar et al., 2020). In the last few years, great efforts have been made in diagnostic and therapeutic techniques. However, the overall survival of patients with GC remains dismal, the median survival being less than 1 year (Smyth et al., 2020). Increasing reports have C Cell ell B Biology iology I International nternational

Adaptation to selective pressures is crucial for clinically important pathogens to establish epidemics, but the underlying evolutionary drivers remain poorly understood. The current epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to public health. In this study we analyzed the genome sequences of 794 CRKP bloodstream isolates collected in 40 hospitals in China between 2014 and 2019. We uncovered a subclonal replacement in the predominant clone ST11, where the previously prevalent subclone OL101:KL47 was replaced by O2v1:KL64 over time in a stepwise manner. O2v1:KL64 carried a higher load of mobile genetic elements, and a point mutation exclusively detected in the recC of O2v1:KL64 significantly promotes recombination proficiency. The epidemic success of O2v1:KL64 was further associated with a hypervirulent sublineage with enhanced resistance to phagocytosis, sulfamethoxazole-trimethoprim, and tetracycline. The phenotypic alterations were linked to the overrepresentation of hypervirulence determinants and antibiotic genes conferred by the acquisition of an rmpA-positive pLVPK-like virulence plasmid and an IncFII-type multidrug-resistant plasmid, respectively. The dissemination of the sublineage was further promoted by more frequent inter-hospital transmission. The results collectively demonstrate that the expansion of O2v1:KL64 is correlated to a repertoire of genomic alterations convergent in a subpopulation with evolutionary advantages.