Search

Identifying gene regulatory networks (GRNs) at the resolution of single cells has long been a great challenge, and the advent of single-cell multi-omics data provides unprecedented opportunities to construct GRNs. Here, we propose a novel strategy to integrate omics datasets of single-cell ribonucleic acid sequencing and single-cell Assay for Transposase-Accessible Chromatin using sequencing, and using an unsupervised learning neural network to divide the samples with high copy number variation scores, which are used to infer the GRN in each gene block. Accuracy validation of proposed strategy shows that approximately 80% of transcription factors are directly associated with cancer, colorectal cancer, malignancy and disease by TRRUST; and most transcription factors are prone to produce multiple transcript variants and lead to tumorigenesis by RegNetwork database, respectively. The source code access are available at: https://github.com/Cuily-v/Colorectal_cancer.

Background: Few studies have explored the correlation between asthma medication and features on HRCT images. We aim to analyse the differences and temporal changes of lung function and airway resistance in asthma with diverse HRCT phenotypes in a short period after inhalation of budesonide/formoterol. Method: This observational study recruited 55 adult patients with varying severities of asthma. We performed detailed airway metrics measurements of chest CT scans, such as airway wall thickness (WT), wall area percentage (WA%), wall thickness percentage (T/OR), and airways with an inner perimeter of 10 mm (Pi10). The effect of lung structural features on asthma medication response was explored according to the WA% and T/OR twelve hours post-drug administration. Using multivariable regression models, we then assessed the influence of WA% on lung function. Results: WA% (p < 0.001) and T/OR (p < 0.001) significantly increased in asthma than in healthy control subjects. Compared to mild asthma, airway walls were further thickened (WA%, p = 0.023; T/OR: p = 0.029) and associated with lumen narrowing (Pi10, p = 0.055) in moderate to severe asthma. WA% and T/OR correlated well with lung function (FEV1, FVC, MMEF, and PEF) and airway resistance (R5, R20, Rp, and Fres). Regression analysis showed that MEF25 decreased with increasing age and WA% (R2 = 0.58, p < 0.001). Patients with thickened airway walls experienced a maximal increase in FVC, FEV1, and PEF at 2 h (p < 0.001) and a maximal decrease of R5, Z5, and Rp at 2 h (p < 0.001) in those with a thickened airway pattern. Conclusions: Asthma patients with different bronchial wall thicknesses exhibited variable lung function changes. Specifically, patients with thick airway wall patterns were more sensitive to inhaled budesonide in the short term.

Methods Forty-four COVID-19 patients (severe/critical: N = 8, non-severe: N = 36) were examined by next generation sequencing (NGS) of nasopharyngeal test paper to observe the effect of novel coronavirus infection to the microbial composition in upper airway. Results In these nasopharyngeal test paper samples, 38 kinds of bacteria, 10 kinds of viruses except SARS-CoV-2, nine kinds of fungi and three kinds of atypical pathogens had been found. There was some difference in microbial composition in the upper airway between severe and non-severe cases. Summary These results are important for us to study the effect of SARS-CoV-2 on the local microbial composition of upper airway and prevent opportunistic infection in severe patients.

Summary: Background: The global dissemination of colistin resistance encoded by mcr-1 has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence of mcr-1 in common pathogens, such as Escherichia coli, is of particular concern. China banned the use of colistin in animal feed from May 1, 2017. We investigated subsequent changes in mcr-1 prevalence in animals, humans, food, and the environment, and the genomic epidemiology of mcr-1-positive E coli (MCRPEC). Methods: Sampling was done before (October to December, 2016) and after (October to December, 2017, and 2018, respectively) the colistin ban. 3675 non-duplicate pig faecal samples were collected from 14 provinces (66 farms) in China to measure intervention-related changes in mcr-1 prevalence. 15 193 samples were collected from pigs, healthy human volunteers, patients colonised or infected with Enterobacteriaceae who were admitted to hospital, food and the environment in Guangzhou, to characterise source-specific mcr-1 prevalence and the wider ecological effect of the ban. From these samples, 688 MCRPEC were analysed with whole genome sequencing, plasmid conjugation, and S1 pulsed-field gel electrophoresis with Southern blots to characterise associated genomic changes. Findings: After the ban, mcr-1 prevalence decreased significantly in national pig farms, from 308 (45%) of 684 samples in 2016 to 274 (19%) of 1416 samples in 2018 (p

Tumor cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect, but the involvement of Warburg effect in liver cancer cell metastasis is not well understood. In present study, our results indicate a positive correlation between glucose metabolism level and metastatic potential of hepatocellular carcinoma (HCC). We also observed that a long noncoding RNA-SOX2OT (lncRNA-SOX2OT) can not only increase the metastatic potential of HCC but also promote a pyruvate kinase M2 (PKM2)-mediated activation of glucose metabolism. Inhibition of PKM2 in HCC cells greatly compromises lncRNA-SOX2OT in promoting Warburg effect and metastasis. Furthermore, miR-122-5p was found being a direct target of lncRNA-SOX2OT in regulating PKM2 expression. Thus, our findings reveal that lncRNA-SOX2OT, a regulator of PKM2, could predispose HCC patients to metastases and may serve as a candidate for metastatic prediction and therapies in HCC patients.

Yingjian Liang,1,* Lidi Qiu,2,* Xiaobin Zheng,1 Jing Liu1 1Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, People’s Republic of China; 2Department of Infectious Disease Intensive Care Unit, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Liu; Xiaobin ZhengDepartment of Pulmonary and Critical Care Medicine (PCCM), Fifth Affiliated Hospital of Sun Yat-sen University, 52 East Meihua Road, Zhuhai City, 519000, People’s Republic of ChinaTel/Fax +867562528733Email liujing25@mail.sysu.edu.cn; zhxbin@mail.sysu.edu.cnAbstract: In this report, we analyze the trends in antimicrobial resistance of Staphylococcus aureus according to the last 15-year-period reports of the China Antimicrobial Surveillance Network (CHINET). It is encouraging that there is a decreasing MRSA proportion in the infection of adults as well as better activity of non-beta-lactam agents in vitro in recent years. However, childhood MRSA infection as well as the tigecycline-resistant MRSA isolate in China deserves increasing concern.Keywords: Staphylococcus aureus, antimicrobial resistance, China Antimicrobial Surveillance Network

Background: DNA methylation is an important epigenetic modification, which plays an important role in regulating gene expression at the transcriptional level. In tumor research, it has been found that the change of DNA methylation leads to the abnormality of gene structure and function, which can provide early warning for tumorigenesis. Our study aims to explore the relationship between the occurrence and development of tumor and the level of DNA methylation. Moreover, this study will provide a set of prognostic biomarkers, which can more accurately predict the survival and health of patients after treatment.Methods: Datasets of bladder cancer patients and control samples were collected from TCGA database, differential analysis was employed to obtain genes with differential DNA methylation levels between tumor samples and normal samples. Then the protein-protein interaction network was constructed, and the potential tumor markers were further obtained by extracting Hub genes from subnet. Cox proportional hazard regression model and survival analysis were used to construct the prognostic model and screen out the prognostic markers of bladder cancer, so as to provide reference for tumor prognosis monitoring and improvement of treatment plan.Results: In this study, we found that DNA methylation was indeed related with the occurrence of bladder cancer. Genes with differential DNA methylation could serve as potential biomarkers for bladder cancer. Through univariate and multivariate Cox proportional hazard regression analysis, we concluded that FASLG and PRKCZ can be used as prognostic biomarkers for bladder cancer. Patients can be classified into high or low risk group by using this two-gene prognostic model. By detecting the methylation status of these genes, we can evaluate the survival of patients.Conclusion: The analysis in our study indicates that the methylation status of tumor-related genes can be used as prognostic biomarkers of bladder cancer.

Awareness of the management of coronavirus disease 2019 (COVID-19) and airway diseases can effectively help clinical physician during the coronavirus pandemic. Herein, we elucidated a COVID-19 case coexisting with severe asthma. Budesonide/glycopyrrolate/formoterol fumarate (BGF) was used as sequential medicine to systemic glucocorticoids for his persisted symptoms related to bronchospasms. Our case suggests patients with long-term airway diseases like asthma probably attribute their symptoms to COVID-19 instead of primary diseases, which make it more difficult in the symptom control. BGF is able to be an effective and convenient choice as sequential medicine to systemic glucocorticoids in some refractory asthmatic patients complicated with COVID-19.

Yingjian Liang, Xiaobin Zheng, Meizhu Chen, Changli Tu, Cuiyan Tan, Yiying Huang, Zhenguo Wang, Jian Wu, Jing Liu Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of ChinaCorrespondence: Jing Liu; Xiaobin ZhengDepartment of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, 52 East Meihua Road, Zhuhai City, 519000, People’s Republic of ChinaTel/Fax +867562528733Email liujing25@mail.sysu.edu.cn; zhxbin@mail.sysu.edu.cnPurpose: The main objective of this study was to decipher the general epidemiology, clinical characteristic, laboratory finding and chest computed tomography (CT) imaging features of the novel coronavirus disease (COVID-19) patients whose initial detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)is negative.Methods: Nearly 100 confirmed cases admitted to The Fifth Affiliated Hospital of Sun Yat-sen University from 18th January to 26th February, 2020, were screened. Clinical records, laboratory results and CT images were reviewed for nine COVID-19 patients with initially negative RT-PCR detection.Results: Fever and cough were common, and one patient merely present gastrointestinal symptoms. Increasing CRP and decreasing ALB were showed in nearly half of the patients among negative detection and return to normal level after real time polymerase chain reaction (RT-PCR) results converted from positive to negative. Left lower lobe was affected nearly in all the patients. A patient received oxygen support timely according his high Mulbsta score.Conclusion: Our study elucidated on the clinical features of hospitalized patients with initially negative detection of SARS-CoV nucleic acid. Patient merely with symptoms associated with digestive system should be screened for COVID-19. CT scan and repeated RT-PCR are two powerful diagnostic tools. Mulbsta score assessing in the early stage enhances the confidence of severity evaluation in physician.Keywords: COVID-19, negative detection, clinical characteristic, laboratory finding, CT images features

Purpose: As a main rate-limiting subunit of the 2-oxoglutarate dehydrogenase multienzyme complex, oxoglutarate dehydrogenase like (OGDHL) is involved in the tricarboxylic acid cycle, and frequently downregulated in human carcinoma and suppresses tumor growth. However, little is known about the role of OGDHL in human cancer, especially pancreatic cancer. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by OGDHL modulating pancreatic cancer progression. Experimental Design: The expression and functional analysis of OGDHL, miR-214, and TWIST1 in human pancreatic cancer tissues, cell lines, and xenograft tumor model were investigated. The correlations between OGDHL and those markers were analyzed. Results: OGDHL was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. OGDHL was shown to be negatively regulated by miR-214. TWIST1 upregulation induced miR-214 expression in pancreatic cancer. OGDHL suppressed TWIST1 expression through promoting ubiquitin-mediated proteasomal degradation of HIF1α and regulating AKT pathways. A combination of OGDHL downregulation and TWIST1 and miR-214 overexpression predicted worse prognosis in patients with pancreatic cancer. Conclusions: We demonstrated the prognostic value of OGDHL, miR-214, and TWIST1 in pancreatic cancer, and elucidated a novel pathway in OGDHL-regulated inhibition of pancreatic cancer tumorigenesis and metastasis. These findings may lead to new targeted therapy for pancreatic cancer through regulating OGDHL, miR-214, and TWIST1.

Purpose: The discovery of the plasmid-mediated colistin resistance genes, mcr, revealed a mechanism of transmission of colistin resistance, which is a major, global public health concern especially among individuals infected with carbapenem-resistant Gram-negative bacteria. To monitor the spread and epidemiology of mcr genes, a convenient and reliable method to detect mcr genes in clinical isolates is needed, especially in the primary care institutions. This study aimed to establish a restriction endonuclease-based multiplex loop-mediated isothermal amplification (multi-LAMP) assay to detect mcr genes (mcr-1 to mcr-5) harbored by colistin-resistant bacteria. Methods: A triple-LAMP assay for mcr-1, mcr-3, and mcr-4 and a double-LAMP assay for mcr-2 and mcr-5 were established. The sensitivity and specificity of the LAMP reactions were determined via electrophoresis and visual detection. Results: The sensitivity of the LAMP assay was 10-fold greater than that of PCR, with high specificity among the screened primers. Specific mcr genes were distinguished in accordance with band numbers and the fragment length of the digested LAMP amplification products. Furthermore, the LAMP assay was confirmed as a rapid and reliable diagnostic technique upon application for clinical samples, and the results were consistent with those of conventional PCR assay. Conclusion: The multi-LAMP assay is a potentially promising method to detect mcr genes and will, if implemented, help prevent infections by drug-resistant bacteria in primary-care hospitals due to rapid and reliable surveillance. To our knowledge, this is the first study to report the application of LAMP to detect mcr-2 to mcr-5 genes and the first time that multi-LAMP has been applied to detect mcr genes.

Purpose The main objective of this study was to decipher the prevalence, antimicrobial resistance, major virulence genes and the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolated from different clinical sources in southern China. Materials and methods The present study was performed on 187 non-duplicate S. aureus clinical isolates collected from three tertiary hospitals in Guangdong Province, China, 2010-2016. Antimicrobial susceptibility testing was performed by the disk diffusion method and by measuring the minimum inhibitory concentration. Screening for resistance and virulence genes was performed. Clonal relatedness was determined using various molecular typing methods such as multilocus sequence typing, spa and staphylococcal chromosomal cassette mec (SCCmec) typing. Whole genome sequencing was performed for three selected isolates. Results Out of 187 isolates, 103 (55%) were identified as MRSA. The highest prevalence rate was found among the skin and soft tissue infection (SSTI) samples (58/103), followed by sputum samples (25/103), blood stream infection samples (15/103) and others (5/103). Antimicrobial susceptibility results revealed high resistance rates for erythromycin (64.1%), clindamycin (48.5%), gentamicin (36.9%) and ciprofloxacin (33.98%). All isolates were susceptible to vancomycin. Resistance genes and mutation detected were as follows: aac(6')-aph(2") (24.3%), dfrG (10.7%), rpoB (21.4%), cfr (0%), fexA (1.94%), gyrA (35.92%), gyrB (0.97%), grlA (20.4%), grlB (10.68%), ermA (21.4%), ermB (18.44%), ermC (21.4%) and lnuA (18.44%). Profiling of virulence genes revealed the following: sea (11.7%), seb (21.4%), sec (0.97%), sed (0.97%), hla (86.41%), hlb (17.48%), hlg (10.68%), hld (53.4%), Tsst-1 (3.9%) and pvl (27.2%). Clonal relatedness showed that ST239-SCCmecA III-t37 clone was the most prevalent clone. Conclusion Our study elucidated the prevalence, antibiotic resistance, pathogenicity and molecular characteristics of MRSA isolated from various clinical sources in Guangdong, China. We found that the infectious rate of MRSA was higher among SSTI than other sources. The most predominant genotype was ST239-SCCmecA III-t37 clone, indicating that ST239-t30 clone which was previously predominant had been replaced by a new clone.

BackgroundImpulse oscillometry (IOS) can be used to evaluateairway impedance in patients with obstructive airway diseases. Previous studies have demonstrated that IOS parameters differ betweenbronchiectasis patients and healthy controls. This study aims to explore the usefulness of IOS in assessing disease severity and airway reversibility in bronchiectasis.MethodSeventy-four patients with non-cystic fibrosis bronchiectasis who visited our Respiratory Medicine outpatient clinic were consecutively recruited. Spirometry, plethysmography and IOS tests were performed. Patients were stratified into mild, moderate and severe disease according to Reiff, Bhalla, BSI, FACED, and BRICS scores. Airway reversibility was measured by bronchodilation test (BDT) and the result was classified as positive or negative.. ROC curves of IOS parameters was used to assess the usefulness of IOS parameters in predicting airway reversibility. Correlations between the IOS, spirometric lung function and bronchiectasis severity parameters were analysed.ResultsMany IOS parameters, such as airway resistance at 5Hz (R5), small airways resistance (R5–R20), total airway reactance (X5), resonance frequency (Fres), total airway impedance at 5Hz (Z5), and peripheral resistance (Rp) increased with increased bronchiectasis severity according to the FACED, BSI and Reiff scores. Large airway resistance (R20) and central resistance (Rc) were not significantly different among groups with differentbronchiectasis severity. The difference between R5 and R20 (R5-R20) showed 81.0% sensitivity, and 69.8%specificity in predicting the airway reversibility in bronchiectasis with AUC of 0.794 (95%CI, 0.672-0.915).ConclusionIOS measurements are useful indicators of bronchiectasis severity and may be useful for predicting the airway reversibility.

In this report, we analyze the trends in antimicrobial resistance of

Background Deaths attributed to Coronavirus Disease 2019 (COVID‐19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID‐19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). Method We detected the serum level of anti‐SARS‐CoV‐2–spike S1 protein‐specific IgE (SP‐IgE) and anti‐SARS‐CoV‐2 nucleocapsid protein‐specific IgE (NP‐IgE) in COVID‐19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID‐19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. Result The levels of serum SP‐IgE and NP‐IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2/FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID‐19. After the application of CS in severe COVID‐19, SP‐IgE and NP‐IgE decreased, but maintained at a high level. Conclusion Hypersensitivity may be involved in severe COVID‐19., Level of IgE to SARS‐CoV‐2–spike protein and nucleocapsid protein positively correlated with clinical severity in COVID‐19 patients. Airway hyperresponsiveness (AHR) exists in early convalescence of COVID‐19. Mast cells with concurrently positive staining for IgE and CD63 were observed in lamina propria of the bronchus and duodenum in severe COVID‐19. We deduce that hypersensitivity reaction may be involved in severe COVID‐19. Note: SP‐IgE: anti‐spike protein (SP) IgE; NP‐IgE: anti‐nucleocapsid protein (NP) IgE; TLSS: Total lung severity scores; BPT: bronchial provocation test; Reff: effective airway resistance; R5‐R20: difference between the resistance at 5 Hz and 20 Hz.

Additional file 1: Supplemental Table 1. Biochemical characteristics of survivor and nonsurvivor surgical sepsis patients on days 1 and 3 after ICU admission.

Background: Dysregulation of RNA binding protein (RBP) expression has been reported in various malignant tumors, and it is related to the occurrence and development of cancer. However, the role of RBPs in colon cancer remains unclear. Methods: We downloaded the RNA sequencing data of colon cancer from The Cancer Genome Atlas (TCGA) database, and determined the differently expressed RBPs between normal and cancer tissues. Then, through a series of bioinformatics analysis, we systematically studied the expression and prognostic value of these RBPs.Result: A total of 490 different expression differently expressed RBPs were identified, including 323 up-regulated and 167 down regulated RBPs. Five RBPs (PNLDC1, NSUN6, NOL3, PPARGC1A, LRRFIP2) were identified as prognosis related genes for the construction of prognostic model. Further analysis showed that the overall survival rate (OS) of patients in the high-risk subgroup was worse than that in the low-risk subgroup based on this model. The area under the characteristic curve of time-dependent receiver was 0.691 in TCGA and 0.624 in GEO, which confirmed the prognostic model to be a good one. We also established a nominal map based on the internal validation in 5 RBPs mRNAs and TCGA sequeues, showing a good ability to differentiate colon cancer.Conclusions: We screened RBPs expression differences between colon cancer and adjacent non tumor colon tissues using the TCGA database to identify potential gene biomarkers.Besides,a very effective prediction model was constructed and tested based on the differential expression of RBPs using the TCGA and Gene Expression Omnibus (GEO) database.We also Validated of the relationship between the expression of five RBPs and prognosis

Background Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner. Methods This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve. Results Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset. Conclusions We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.

Background Soluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and in surgical sepsis patients (SS) during the first three days at Intensive Care Unit (ICU) admission, and to observe the association between sCD40L and mortality. Methods Time changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with 19 SWS. Serum sCD40L concentration was detected by ELISA. Survival at 28-days was used as the endpoint. Results SS had significantly higher sCD40L levels than SWS and control patients. Advanced age (P = 0.023) was observed in the group of nonsurviving patients compared with surviving SS. We observed an association between sCD40L levels ≥ 1028.75 pg/ml at day 2 and 28-days mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007). Conclusions Septic patients show persistently higher circulating sCD40L levels in the first three days at ICU admission, and it is likely that sCD40L on the day 2 may have a predictive value; thus, serum sCD40L could be used as a reliable biomarker and therapeutic target in sepsis.

COVID-19 has raised worldwide concern as spiraling into a pandemic. Reports about comprehensive investigation of COVID-19 viremia are extremely scanty. Herein, we present four COVID-19 patients with positive SARS-CoV-2 nucleic acid test in blood, accounting for 12.12% of 33 detected cases. Rapid deterioration of these cases with septic shock, accompanying with lung CT images enlarged rapidly, decrease of blood oxygen, heart rate drop (with asynchrony of hypoxemia) accompanied with SARS-CoV-2 viremia. It indicates that massive replication and releasing into blood of SARS-CoV-2 and secondary inflammation storm may lead to injury of multiple organs and poor prognosis. So, positive COVID-19 nucleic acid test in blood may be a good forecasting marker of rapid deterioration of COVID-19 pneumonia. In addition, clearance of viremia may indicate tendency for recovery.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of a public health emergency in the world, accompanying with high mortality in severe corona virus disease 2019(COVID-19 ), thereby early detection and stopping the progress to severe COVID-19 is important. Our aim is to establish a clinical nomogram model to calculate and predict the progress to severe COVID-19 timely and efficiently.Methods: In this study, 65 patients with COVID-19 had been included retrospectively in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, to February 11, 2020. Patients were randomly assigned to train dataset (n=51 with 15 progressing to severe COVID-19) and test dataset (n=14 with 4 progressing to severe COVID-19). Lasso algorithm was applied to filter the most classification relevant clinical factors. Based on selected factors, logistic regression model was fit to predict the severe from mild/common. Meanwhile in nomogram sensitivity, specificity, AUC (Area under Curve), and calibration curve were depicted and calculated by R language, to evaluate the prediction performance to severe COVID-19.Results:High ratio of sever COVID-19 patients (26.5%) had been found in our retrospective study, and 84% of these cases progress to severe or critical after 5 days from their first clinical examination. In these 65 patients with COVID-19, 77 clinical characteristics in first examination were collected and analyzed, and 37 ones had been found different between non-severe and severe COVID-19. But when all these factors were analyzed in establishment of prediction model, six factors are crucial for predicting progress of severe COVID-19 via Lasso algorithm. Based on these six factors, including increased fibrinogen, hyponatremia, decreased PaO2,multiple lung lobes involved, down-regulated CD3（+）T-lymphocyte and fever, a logistic regression model was fit to discriminate severe and common COVID-19 patients. The sensitivity, specificity and AUC were 0.93, 0.86, 0.96 in the train dataset and 0.9, 1.0, 1.0 in test dataset respectively. Nomogram-predicted probability was more consistent with actual probability by R language.Conclusions:In summary, an efficient and reliable clinical nomogram model had been established, which indicate increased fibrinogen, hyponatremia, decreased PaO2, multiple lung lobes involved, down-regulated CD3（+）T-lymphocyte and fever at the first clinical examination, could predict progress of patients to severe COVID-19.

BackgroundThe global dissemination of colistin resistance encoded by mcr-1 has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence of mcr-1 in common pathogens, such as Escherichia coli, is of particular concern. Therefore, China banned the use of colistin in animal feed from May 1ST 2017. We investigated subsequent changes in mcr-1 prevalence, and the genomic epidemiology of mcr-1-positive Escherichia coli (MCRPEC).MethodsSampling was conducted pre- (October-December 2016) and post-colistin ban (October-December, 2017 and 2018, respectively). 3675 non-duplicate pig fecal samples were collected from 14 provinces (66 farms) in China to determine intervention-related changes in mcr-1 prevalence. 15193 samples were collected from pigs, healthy human volunteers, colonized and infected hospital inpatients, food and the environment in Guangzhou, to characterize source-specific mcr-1 prevalence and the wider ecological impact of the ban. From these samples, 688 MCRPEC were analyzed with whole genome sequencing (WGS), plasmid conjugation and S1-PFGE/Southern blots to characterize associated genomic changes.FindingsAfter the ban, mcr-1 prevalence decreased significantly in national pig farms, from 45·0% (308/684 samples) in 2016, to 19·4% (274/1416) in 2018 (pmcr-1 was predominantly found on plasmids (632/688 [92%]). Common mcr-1 plasmid types included IncX4, IncI2 and IncHI2 (502/656 [76.5%]); significant increases in IncI2-associated mcr-1 and a distinct lineage of mcr-1-associated IncHI2 were observed post-ban. Changes in the frequency of mcr-1-associated flanking sequences (ISApl1-negative MCRPEC), 63 core genome SNPs and 30 accessory genes were also significantly different after the ban, consistent with rapid genetic adaptation in response to changing selection pressures.InterpretationA rapid, ecosystem-wide, decline in mcr-1 was observed after banning the use of colistin in animal feed, with associated genetic changes in MCRPEC. Genomic surveillance is key to assessing and monitoring stewardship interventions.FundingNational Natural Science Foundation of China

Immune cell death caused by neutrophil extracellular traps (NETs), referred to as NETosis, can contribute to the pathogenesis of endotoxemia and organ damage. Although the mechanisms by which infection induces NETosis and how that leads to organ dysfunction remain largely unknown, NET formation is often found following citrullination of histone H3 (CitH3) by peptidylarginine deiminase (PAD). We hypothesized that lipopolysaccharide (LPS)-induced activation of PAD and subsequent CitH3-mediated NET formation increases endothelial permeability and pulmonary dysfunction and, therefore, that inhibition of PAD can mitigate damage and improve survival in lethal endotoxemia. Here, we showed that treatment with YW3–56, a PAD2/PAD4 inhibitor, significantly diminished PAD activation, blocked LPS-induced pulmonary vascular leakage, alleviated acute lung injury, and improved survival in a mouse model of lethal LPS-induced endotoxemia. We found CitH3 in the bloodstream 30 min after intraperitoneal injection of LPS (35 mg/kg) into mice. Additionally, CitH3 production was induced in cultured neutrophils exposed to LPS, and NETs derived from these LPS-treated neutrophils increased the permeability of endothelial cells. However, YW3–56 reduced CitH3 production and NET formation by neutrophils following LPS exposure. Moreover, treatment with YW3–56 decreased the levels of circulating CitH3 and abolished neutrophil activation and NET formation in the lungs of mice with endotoxemia. These data suggest a novel mechanism by which PAD-NET-CitH3 can play a pivotal role in pulmonary vascular dysfunction and the pathogenesis of lethal endotoxemia.

Background Hepatocellular carcinoma (HCC) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of HCC progression is critical for the identification of new therapeutic targets for HCC. This study aimed to determine the role of Non-SMC condensin II complex subunit G2 (NCAPG2) in HCC proliferation and metastasis. Methods We detected NCAPG2 expression in tissues using immunohistochemistry, western blotting and real-time PCR. The effects of NCAPG2 on cell proliferation and metastasis were evaluated both in vitro and in vivo. Immunocytochemistry, enzyme linked immunosorbent assay, co-immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanisms. Findings We found that NCAPG2 is frequently upregulated in HCC tumour tissues and predicts a poor prognosis. NCAPG2 overexpression promotes HCC proliferation, migration, and invasion through activating STAT3 and NF-κB signalling pathways. Moreover, NCAPG2 is a direct target of miR-188-3p. We demonstrated the existence of a positive feedback loop between NCAPG2 and p-STAT3 and a negative feedback loop between NCAPG2 and miR-188-3p. Interpretation Our study indicates that NCAPG2 overexpression could drive HCC proliferation and metastasis through activation of the STAT3 and NF-κB/miR-188-3p pathways. These findings may contribute to the identification of novel biomarkers and therapeutic targets for HCC. Fund National Key Program for Science and Technology Research and Development (Grant No. 2016YFC0905902); the National Natural Scientific Foundation of China (Nos. 81772588, 81602058, 81773194); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT-2016200); the Innovative Research Program for Graduate of Harbin Medical University (Grant Nos. YJSCX2017-38HYD, YJSCX2016-18HYD).

Here, we identified mcr-4.3 in Acinetobacter baumannii, which had not been previously observed to carry an mcr gene. The mcr-4.3-harboring A. baumannii strain AB18PR065 was isolated from pig feces from a slaughterhouse in Guangdong Province of China. The mcr-4.3-carrying pAB18PR065 is 25,602 bp in size and could not be transferred in conjugation, transformation, and electroporation experiments, as we did not find any conjugation-related genes therein. pAB18PR065 harbors two copies of type II toxin-antitoxin systems, which are functional in plasmid stabilization and maintenance. pAB18PR065 shares similarity only with one recently identified plasmid, pAb-MCR4.3 (35,502 bp), from a clinical A. baumannii strain. It is likely that the emergence of pAb-MCR4.3 was due to the insertion of an 11,386-bp, ISAba19-based, composite transposon into pAB18PR065. These data indicate that mcr-4.3 was captured by an A. baumannii-original plasmid via horizontal gene transfer.