Eicosapentaenoic acid activates the P62/KEAP1/NRF2 pathway for the prevention of diabetes-associated cognitive dysfunction.

Diabetes-associated cognitive dysfunction (DCD) is a severe complication of diabetes mellitus (DM), threatening the life quality of the diabetic population. However, there is still a lack of effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that was not previously investigated for its effect on DCD. In this study, EPA was found to improve DCD in a mouse model of type 2 DM (T2DM) induced by streptozotocin and a high-fat diet, exhibiting profound protective effects on cognitive dysfunction, neuronal loss, and cerebral oxidative stress and inflammation. While EPA did not attenuate advanced glycation end product-induced neuron injury, we hypothesized that EPA might protect neurons by regulating microglia polarization, the effect of which was confirmed by the co-culture of neurons and lipopolysaccharide-stimulated microglia. RNA sequencing identified nuclear factor-erythroid-2-related factor 2 (NRF2) antioxidant signaling as a major target of EPA in microglia. Mechanistically, EPA increased sequestosome-1 (SQSTM1 or P62) levels that might structurally inhibit Kelch-like ECH associated protein 1 (KEAP1), leading to nuclear translocation of NRF2. P62 and NRF2 predominantly mediated EPA's effect since the knockdown of P62 or NRF2 abolished EPA's protective effect on microglial oxidative stress and inflammation and sequential neuron injuries. Moreover, the regulation of P62/KEPA1/NRF2 axes by EPA was confirmed in the hippocampi of diabetic mice. The present work presents EPA as an effective nutritional approach and microglial P62/KEAP1/NRF2 as molecular targets for the intervention of DCD.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in recurrent pancreatitis of pediatric asparaginase-associated pancreatitis.

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

Intracellular metabolic profiling of drug resistant cells by surface enhanced Raman scattering.

BACKGROUND: Intracellular metabolic profiling reveals real-time metabolic information useful for the study of underlying mechanisms of cells in particular conditions such as drug resistance. However, mass spectrometry (MS), one of the leading metabolomics technologies, usually requires a large number of cells and complex pretreatments. Surface enhanced Raman scattering (SERS) has an ultrahigh detection sensitivity and specificity, favorable for metabolomics analysis. However, some targeted SERS methods focus on very limited metabolite without global bioprofiling, and some label-free approaches try to fingerprint the metabolic response based on whole SERS spectral classification, but comprehensive interpretation of biological mechanisms was lacking. (95) RESULTS: We proposed a label-free SERS technique for intracellular metabolic profiling in complex cellular lysates within 3 min. We first compared three kinds of cellular lysis methods and sonication lysis shows the highest extraction efficiency of metabolites. To obtain comprehensive metabolic information, we collected a spectral set for each sample and further qualified them by the Pearson correlation coefficient (PCC) to calculate how many spectra should be acquired at least to gain the adequate information from a statistical and global view. In addition, according to our measurements with 10 pure metabolites, we can understand the spectra acquired from complex cellular lysates of different cell lines more precisely. Finally, we further disclosed the variations of 22 SERS bands in enzalutamide-resistant prostate cancer cells and some are associated with the androgen receptor signaling activity and the methionine salvage pathway in the drug resistance process, which shows the same metabolic trends as MS. (149) SIGNIFICANCE: Our technique has the capability to capture the intracellular metabolic fingerprinting with the optimized lysis approach and spectral set collection, showing high potential in rapid, sensitive and global metabolic profiling in complex biosamples and clinical liquid biopsy. This gives a new perspective to the study of SERS in insightful understanding of relevant biological mechanisms. (54).

Independent prognostic value of the congestion and renal index in patients with acute heart failure.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Triggering pyroptosis enhances the antitumor efficacy of PARP inhibitors in prostate cancer.

PURPOSE: PARP inhibitors have revolutionized the treatment landscape for advanced prostate cancer (PCa) patients who harboring mutations in homologous recombination repair (HRR) genes. However, the molecular mechanisms underlying PARP inhibitors function beyond DNA damage repair pathways remain elusive, and identifying novel predictive targets that favorably respond to PARP inhibitors in PCa is an active area of research. METHODS: The expression of GSDME in PCa cell lines and human PCa samples was determined by western blotting. Targeted bisulfite sequencing, gene enrichment analysis (GSEA), clone formation, construction of the stably transfected cell lines, lactate dehydrogenase (LDH) assay, western blotting as well as a mouse model of subcutaneous xenografts were used to investigate the role of GSDME in PCa. The combinational therapeutic effect of olaparib and decitabine was determined using both in vitro and in vivo experiments. RESULTS: We have found low expression of GSDME in PCa. Interestingly, we demonstrated that GSDME activity is robustly induced in olaparib-treated cells undergoing pyroptosis, and that high methylation of the GSDME promoter dampens its activity in PCa cells. Intriguingly, genetically overexpressing GSDME does not inhibit tumor cell proliferation but instead confers sensitivity to olaparib. Furthermore, pharmacological treatment with the combination of olaparib and decitabine synergistically induces GSDME expression and cleavage through caspase-3 activation, thus promoting pyroptosis and enhancing anti-tumor response, ultimately resulting in tumor remission. CONCLUSION: Our findings highlight a novel therapeutic strategy for enhancing the long-term response to olaparib beyond HRR-deficient tumors in PCa, underscoring the critical role of GSDME in regulating tumorigenesis.

Domain adaptive Sim-to-Real segmentation of oropharyngeal organs.

Video-assisted transoral tracheal intubation (TI) necessitates using an endoscope that helps the physician insert a tracheal tube into the glottis instead of the esophagus. The growing trend of robotic-assisted TI would require a medical robot to distinguish anatomical features like an experienced physician which can be imitated by utilizing supervised deep-learning techniques. However, the real datasets of oropharyngeal organs are often inaccessible due to limited open-source data and patient privacy. In this work, we propose a domain adaptive Sim-to-Real framework called IoU-Ranking Blend-ArtFlow (IRB-AF) for image segmentation of oropharyngeal organs. The framework includes an image blending strategy called IoU-Ranking Blend (IRB) and style-transfer method ArtFlow. Here, IRB alleviates the problem of poor segmentation performance caused by significant datasets domain differences, while ArtFlow is introduced to reduce the discrepancies between datasets further. A virtual oropharynx image dataset generated by the SOFA framework is used as the learning subject for semantic segmentation to deal with the limited availability of actual endoscopic images. We adapted IRB-AF with the state-of-the-art domain adaptive segmentation models. The results demonstrate the superior performance of our approach in further improving the segmentation accuracy and training stability.

The crosslink between the hyaluronic acid and drugs treated by reactive oxygen species produced in plasma based on the molecular dynamics simulation.

Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children: A multicenter randomized controlled trial.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

Long-term exposure to low-dose Di(2-ethylhexyl) phthalate aggravated high fat diet-induced obesity in female mice.

The potential obesogenic roles of di(2-ethylhexyl) phthalate (DEHP) have attracted great attention. The current study aimed to evaluate the combined effects of chronic low-dose DEHP (0.05 mg/kg BW) and a high-fat diet (HFD) on obesity in female mice and explore the underlying mechanisms. We found that low-dose DEHP challenge for 29 weeks increased fat accumulation both in CD- and HFD-fed mice and significantly accelerated the weight gain without affecting food intake in HFD-fed mice. DEHP exposure reduced the energy metabolism, down-regulated the uncoupling protein 1 (UCP1) and total oxidative phosphorylation (OXPHOS) proteins expression in the brown adipose tissue, and up-regulated the PPARγ expression and its phosphorylation at Ser273 in white adipose tissue (WAT). Besides, the combination of DEHP and HFD drove the remodeling of gut microbiota of mice, characterized by the reduced richness and diversity and the elevated Firmicutes to Bacteroidetes (F/B) ratio. Short-chain fatty acids (SCFAs) analysis revealed that DEHP and HFD cotreatment led to a decrease in levels of acetic acid, butyric acid, and pentanoic acid. Interestingly, sodium butyrate (NaB) significantly inhibited the adipogenesis and lipid accumulation of NIH/3T3 mouse embryonic fibroblasts (PPARγ2 overexpression) and the PPARγ phosphorylation at Ser273 induced by DEHP or MEHP. These findings demonstrate that chronic low-dose DEHP challenge could prompt fat accumulation by increasing PPARγ phosphorylation at Ser273 and decreasing thermogenesis in BAT, which might be associated with the SCFAs reduction.

Evaluation of RT-LAMP Assay for Rapid Detection of SARS-CoV-2.

OBJECTIVE: To evaluate the accuracy of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in community or primary-care settings. METHOD: We systematically searched the Web of Science, Embase, PubMed, and Cochrane Library databases. We conducted quality evaluation using ReviewManager software (version 5.0). We then used MetaDisc software (version 1.4) and Stata software (version 12.0) to build forest plots, along with a Deeks funnel plot and a bivariate boxplot for analysis. RESULT: Overall, the sensitivity, specificity, and diagnostic odds ratio were 0.79, 0.97, and 328.18, respectively. The sensitivity for the subgroup with RNA extraction appeared to be higher, at 0.88 (0.86-0.90), compared to the subgroup without RNA extraction, at 0.50 (0.45-0.55), with no significant difference in specificity. CONCLUSION: RT-LAMP assay exhibited high specificity regarding current SARS-CoV-2 infection. However, its overall sensitivity was relatively moderate. Extracting RNA was found to be beneficial in improving sensitivity.

Evaluation of CRISPR-Based Assays for Rapid Detection of SARS-CoV-2: A Systematic Review and Meta-Analysis.

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of coronavirus disease 2019. Diagnostic methods based on the clustered regularly interspaced short palindromic repeats (CRISPR) have been developed to detect SARS-CoV-2 rapidly. Therefore, a systematic review and meta-analysis were performed to assess the diagnostic accuracy of CRISPR for detecting SARS-CoV-2 infection. MATERIALS AND METHODS: Studies published before August 2021 were retrieved from four databases, using the keywords "SARS-CoV-2" and "CRISPR." Data were collected from these publications, and the sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic curve was plotted for analysis with MetaDiSc 1.4. The Stata 15.0 software was used to draw Deeks' funnel plots to evaluate publication bias. RESULTS: We performed a pooled analysis of 38 independent studies shown in 30 publications. The reference standard was reverse transcription-quantitative PCR. The results indicated that the sensitivity of CRISPR-based methods for diagnosis was 0.94 (95% CI 0.93-0.95), the specificity was 0.98 (95% CI 0.97-0.99), the PLR was 34.03 (95% CI 20.81-55.66), the NLR was 0.08 (95% CI 0.06-0.10), and the DOR was 575.74 (95% CI 382.36-866.95). The area under the curve was 0.9894. CONCLUSION: Studies indicate that a diagnostic method based on CRISPR has high sensitivity and specificity. Therefore, this would be a potential diagnostic tool to improve the accuracy of SARS-CoV-2 detection.

Accuracy of cytokeratin 19 fragment in the diagnosis of bladder cancer.

Aim: CYFRA21-1 is a biomarker of cancer and has a promising future in the diagnosis of bladder cancer. The purpose of this study was to assess the diagnostic accuracy of CYFRA21-1 for bladder cancer. Methods: We included articles from the Cochrane Library, Web of Science, PubMed and Embase. Meta-DiSc 1.4 and Stata 12.0 were used for data analysis. Results: Twenty-eight articles were analyzed, and the results are as follows: sensitivity, specificity, PLR, NLR, DOR and AUC were 0.69 (95% CI [0.67, 0.71]), 0.81 (95% CI [0.80, 0.83]), 5.99 (95% CI [4.42, 8.11]), 0.31 (95% CI [0.25, 0.38]), 24.58 (95% CI [15.15, 39.89]) and 0.8917, respectively. Conclusion: CYFRA21-1 has a high diagnostic efficiency for bladder cancer.

Diagnostic Accuracy of Xpert Xpress Flu/RSV for the Detection of Influenza and Respiratory Syncytial Viruses.

Xpert Xpress Flu/RSV is a fast and automated real-time nucleic acid amplification tool for detecting influenza virus and respiratory syncytial virus (RSV). The aim of this study was to verify the accuracy of Xpert Xpress Flu/RSV for detecting influenza virus and RSV. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched up to October 2020. The quality of the original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 guidelines. Meta-DiSc 1.4 software was used to analyze the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve. Deek's funnel plot asymmetry test was used to evaluate the publication bias using the Stata 12.0 software. Ten studies with 25 fourfold tables were included in the analysis. The sensitivity of Xpert Xpress Flu/RSV for detecting influenza A, influenza B, and RSV were 0.97, 0.98, and 0.96, respectively, and the specificities were 0.97, 1.00, and 1.00, respectively. Compared with other common clinical real-time reverse transcription-polymerase chain reaction (RT-PCR), Xpert Xpress Flu/RSV is a valuable tool for diagnosing influenza virus and RSV with high sensitivity and specificity.

Identification of Key Pathways and Genes in SARS-CoV-2 Infecting Human Intestines by Bioinformatics Analysis.

COVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein-protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.

Meta-Analysis of the Diagnostic Efficacy of the Luminex xTAG Respiratory Viral Panel FAST v2 Assay for Respiratory Viral Infections.

PURPOSE: Acute respiratory viral infections pose significant morbidity and mortality, making it essential to diagnose respiratory viral infections rapidly. In this study, the diagnostic efficacy of the Luminex xTAG Respiratory Virus Panel (RVP) FAST v2 test was evaluated on respiratory viral infections. MATERIALS AND METHODS: Information was retrieved from electronic databases, including Embase, Web of Science, PubMed, and Cochrane Library, for systematic review. Studies that fulfilled predefined inclusion criteria were included. After the extraction of information, statistical software was utilized for quality evaluation, data analysis, and assessment of publication bias. RESULTS: Eighty groups in fourfold tables from nine articles were included to perform statistical analyses. Therein, the mean specificity and mean sensitivity of Luminex xTAG RVP FAST v2 test for the detection of respiratory viral infections were 0.99 (0.98-0.99) and 0.88 (0.87-0.90), respectively. Additionally, the negative and positive likelihood ratios were 0.14 (0.11-0.19) and 87.42 (61.88-123.50), respectively. Moreover, the diagnostic odds ratio and area under the curve of summary receiver operating characteristic were 714.80 and 0.9886, respectively. CONCLUSION: The Luminex xTAG RVP FAST v2 test could be a reliable and rapid diagnostic method for multiple respiratory viral infections.

An integrative bioinformatics analysis for identifying hub genes associated with infection of lung samples in patients infected with SARS-CoV-2.

BACKGROUND: At the end of 2019, the world witnessed the emergence and ravages of a viral infection induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also known as the coronavirus disease 2019 (COVID-19), it has been identified as a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) because of its severity. METHODS: The gene data of 51 samples were extracted from the GSE150316 and GSE147507 data set and then processed by means of the programming language R, through which the differentially expressed genes (DEGs) that meet the standards were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the selected DEGs to understand the functions and approaches of DEGs. The online tool STRING was employed to construct a protein-protein interaction (PPI) network of DEGs and, in turn, to identify hub genes. RESULTS: A total of 52 intersection genes were obtained through DEG identification. Through the GO analysis, we realized that the biological processes (BPs) that have the deepest impact on the human body after SARS-CoV-2 infection are various immune responses. By using STRING to construct a PPI network, 10 hub genes were identified, including IFIH1, DDX58, ISG15, EGR1, OASL, SAMD9, SAMD9L, XAF1, IFITM1, and TNFSF10. CONCLUSION: The results of this study will hopefully provide guidance for future studies on the pathophysiological mechanism of SARS-CoV-2 infection.

Evaluation of Xpert GBS assay and Xpert GBS LB assay for detection of Streptococcus agalactiae.

BACKGROUND: Group B Streptococcal (GBS) infection is the primary agent of neonatal morbidity and mortality. Rapid and simple methods to detect GBS are Xpert GBS and GBS LB assays based on real-time polymerase chain reaction (PCR). However, since the diagnostic accuracy of the two techniques in diagnosing GBS remains unclear, we designed this study to appraise the diagnostic accuracy of the aforementioned. METHODS: A systematic search of all literature published before July 16, 2020 was conducted using Embase, PubMed, Web of Science, and Cochrane Library. The study quality was evaluated through Review Manager 5.3. Accordingly, data extracted in the included studies were analyzed using Meta-DiSc 1.4 and Stata 12.0 software. The diagnosis odds ratio (DOR) and bivariate boxplot were utilized to evaluate the heterogeneity. Publication bias was appraised by using Deeks' funnel plot. RESULTS: A total of 13 studies were adopted and only 19 sets of data met the criteria. The sensitivity and specificity of Xpert GBS were 0.91 (95% CI 0.89-0.92) and 0.93 (95% CI 0.92-0.94). The area under the curve (AUC) was 0.9806. The sensitivity and specificity results of Xpert GBS LB were 0.96 (95% CI 0.95-0.98) and 0.94 (95% CI 0.92-0.95), respectively. The AUC was 0.9950. No publication bias was found. CONCLUSIONS: The Xpert GBS and GBS LB assays are valuable alternative methods with high sensitivity and specificity. However, determining whether they can be used as clinical diagnostic standards for GBS is essential for the future.

Pooled Analysis of the Accuracy of Xpert Ebola Assay for Diagnosing Ebola Virus Infection.

BACKGROUND: West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. METHODS: Using the keywords "Xpert" and "Ebola virus", relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. RESULTS: Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. CONCLUSIONS: Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.

Evaluation of Xpert Carba-R Assay for the Detection of Carbapenemase Genes in Gram-Negative Bacteria.

INTRODUCTION: High mortality associated with carbapenemase-producing Gram-negative bacteria (CP-GNB) has evolved into a global health threat. Rapid and accurate detection as well as prompt treatment are of great significance in this case. Xpert Carba-R, a multiple qualitative analysis designed to detect five clinically relevant carbapenem-resistant gene families within one hour, is regarded as reliable, accurate, and easy-to-operate. This study is to present a systematic evaluation of the performance of Xpert Carba-R in detecting carbapenemase genes in GNB suspected for carbapenemase production. METHODS: We searched and screened the literature on "Xpert Carba-R" in the database of PubMed, Web of Science, Embase, and Cochrane Library, employing two independent evaluators to collect data, respectively. Then, statistical analysis of the data obtained was performed by the Stata 12.0 software to measure the accuracy of Xpert Carba-R assay in detecting the carbapenemase genes in GNB. RESULTS: We screened a total of 1767 Gram-negative bacillus isolates documented in 9 articles. The precision of the detection of OXA-48 carbapenemase genes was 100%; that of NDM = 100%; that of VIM = 100%. When it came to KPC, the precision rate was 100%; that of IMP = 99%. The overall accuracy of the detection of carbapenemase genes was 100%. CONCLUSIONS: Xpert Carba-R assay demonstrates a 100% precision in identifying carbapenemase genes in GNB. It can be seen that Xpert Carba-R method is an effective tool for early clinical detection, which is suitable for the detection of carbapenase gene in GNB.

Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids.

BACKGROUND: In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people's health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein-protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in. RESULTS: In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients. CONCLUSIONS: In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.