Bibliometric analysis of ESKAPE drug‑resistant bacteria / 上海预防医学

ObjectiveTo conduct a bibliometric visual analysis of studies on Enterococcus faecium， Staphylococcus aureus， Klebsiella pneumoniae， Acinetobacter baumannii， Pseudomonas aeruginosa and Enterobacter species （ESKAPE） in the past 10 years at home and abroad， and to analyze current research status and future research directions in this field based on the concept of “One health”. MethodsRelated literature on ESKAPE drug resistant bacteria from 2013 to 2022 was searched on CNKI and WoS， respectively. Furthermore， a metrological visualization analysis of authors， source of agencies， countries， and keywords was conducted by the CiteSpace 6.1.R6 software. ResultsA total of 2 991 pieces of Chinese-language and 24 497 pieces of English-language literature were included in this study. Although the number and growth rate of English-language publications were higher than those of Chinese-language publications， the number of English-language papers authored by Chinese scholars showed a significant upward trend. The level of collaboration between authors and institutions in Chinese-language publications was weaker than that in English-language publications. Overall， the country with the highest number of publications was the United States （6 623）， followed by China （3 776）. However， China’s annual publication volume （851） exceeded that of the United States （600） in 2022. China had collaborations with 25 countries， indicating good global cooperation， but its level of international cooperation was still slightly weaker than that of the United States. High-frequency keywords in Chinese-language literature mainly included drug resistance， nosocomial infection， and antibiotics， while high-frequency keywords in English-language literature included Staphylococcus aureus， Klebsiella pneumoniae， and methicillin-resistant. ConclusionCarbapenem-resistant Klebsiella pneumoniae， carbapenem-resistant Enterobacteriaceae， and "One health" are research hotspots. In the future， cross-sectoral and multi-regional collaboration should be deepened to strengthen the control of infections of important drug-resistant bacteria， and infection treatment strategies should be optimized as well.

Analysis of the genome and transmission characteristics of an aggregated novel coronavirus infection based on metagenomic next-generation sequencing / 中华地方病学杂志

Objective:To analyze the viral genome sequence of novel coronavirus infected persons in Baotou City, understand the mutation characteristics of novel coronavirus genome in the process of transmission among cases, and explore the transmission rule of novel coronavirus in the clustered populations.Methods:Nine throat swabs samples (No. 1 - 7, No. 9, and No. 10), two sputum samples (No. 8, No. 11, and No. 11 sample was from No. 10 case), and one surface smear sample (No.12, and No. 12 sample was from No. 10 case) were collected from 10 confirmed cases of novel coronavirus infection in Baotou City from January 25 to February 21, 2020. Samples 1 and 3 were from single cases, and the rest were from clustered cases. The virus genome was sequenced by metagenomic next-generation sequencing (mNGS), and single nucleotide polymorphism (SNP) mutation sites were screened by comparing with NC_045512, a reference strain of novel coronavirus. Combined with relevant epidemiological information, gene mutation, virus typing, and evolutionary traceability analysis were carried out.Results:The results of viral genome mNGS showed that 76 SNP mutation sites were detected in 12 samples compared with the reference strain NC_045512, including 3 (3.95%) transitions and 73 (96.05%) reversals. There were 19 (25.00%) synonymous mutations and 57 (75.00%) non-synonymous mutations. The analysis of nucleotide and amino acid variation sites showed that mutations were found at five sites (T2821C, C6548T, T16464C, G16858A and T251C) in all the clustered cases (cases 2, 4 - 10). In the single cases, sample 1 had mutations at C9245T and A15340T, and sample 3 had mutation at C13T. The virus typing analysis showed that the samples 1 and 3 belonged to the L type of novel coronavirus, while the rest belonged to the S type of novel coronavirus. The results of genomic evolutionary relationship analysis showed that all the samples could be divided into two branches. The branches of sample 1 and 3 belonged to single cases, and the rest belonged to family clustered cases.Conclusion:The genomic characteristics of the clustered cases of novel coronavirus infection in Baotou City are basically consistent with the epidemiological investigation results, and the transmission of the virus is mainly related to close contact and family gathering.

Guild-level microbiome signature associated with COVID-19 severity and prognosis

COVID-19 severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples collected from 300 in-hospital COVID-19 patients at time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), Redundancy Analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Random Forest model based on these 33 HQMAGs classified patients from different severity groups (average AUC = 0.79). Co-abundance network analysis found that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Random Forest regression showed that these 33 HQMAGs at admission had the capacity to predict 8 clinical parameters, which are predictors for COVID-19 prognosis, at Day 7 in hospital. Moreover, the dominance of Guild 1 over Guild 2 at admission predicted the death/discharge outcome of the critical patients (AUC = 0.92). Random Forest models based on these 33 HQMAGs classified patients with different COVID-19 symptom severity, and differentiated COVID-19 patients from healthy subjects, non-COVID-19, and pneumonia controls in three independent datasets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission.

Current status and prospect of biomarker research for schizophrenia / 中华检验医学杂志

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Bibliometric analysis of status quo and hotspots of health policy research under the concept of One Health based on CiteSpace / 中华地方病学杂志

Objective:To learn about the status quo and hotspots in the field of health policy research under the concept of One Health.Methods:The Web of Science Core Collection (WoS) database and China National Knowledge Infrastructure (CNKI) database from 2001 to 2020 were searched for publications in the field of health policy research under the concept of One Health. A total of 3 515 publications in English and 42 in Chinese were included, CiteSpace 5.6.R3 software was used to analyze the number of publications, countries, institutions, authors, and keywords, and to draw visual maps.Results:The number of publications in WoS database was 52 in 2001 and 500 in 2020, with an overall upward trend in the number of publications; the first relevant publication in CNKI database was published in 2009, and the number of publications increased to 13 by 2020, but the total number was still low (42). Among the countries, the USA had the highest number of publications (1 385), total citations (48 780) and highly cited (≥10 citations) publications (671). Switzerland had the highest citations per publication (89.72). China ranked 5th in the number of publications (160) and 8th in total citations (4 643) and citations per publication (29.02), with fewer highly cited publications (82). The English author partnership had a large collaborative team led by Chris Degeling at the University of Sydney; the Chinese author partnership had a large research team led by Lu Jiahai at the School of Public Health, Sun Yat-sen University. In terms of country cooperation, French node had the largest centrality (0.30), the centrality of Chinese nodes was 0.01. Emerging infectious diseases, zoonose, and antibiotic resistance were high-frequency keywords in the English publications, while COVID-19, zoonose, antibiotic resistance, and food safety were high-frequency keywords in the Chinese publications.Conclusions:From 2001 to 2020, the overall trend of the number of publications in health policy research under the concept of One Health worldwide is on the rise. Emerging infectious diseases, zoonose, antibiotic resistance, and food safety are the current research hotspots in this field.

Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

BackgroundFundamental to viral biology is identification and annotation of viral genes and their function. Determining the level of coronavirus gene expression is inherently difficult due to the positive stranded RNA genome and the identification of sub-genomic RNAs (sgRNAs) that are required for expression of most viral genes. In the COVID-19 epidemic so far, few genomic studies have looked at viral sgRNAs and none have systematically examined the sgRNA profiles of large numbers of SARS-CoV2 datasets in conjuction with data for other coronaviruses. ResultsWe developed a bioinformatic pipeline to analyze the sgRNA profiles of coronaviruses and applied it to 588 individual samples from 20 independent studies, covering more than 10 coronavirus species. Our result showed that SARS-CoV, SARS-CoV-2 and MERS-CoV each had a core sgRNA repertoire generated via a canonical mechanism. Novel sgRNAs that encode peptides with evolutionarily conserved structures were identified in several coronaviruses and were expressed in vitro and in vivo. Two novel peptides may have direct functional relevance to disease, by alluding interferon responses and disrupting IL17E (IL25) signaling. Relevant to coronavirus infectivity and transmission, we also observed that the level of Spike sgRNAs were significantly higher in-vivo than in-vitro, while the opposite held true for the Nucleocapside protein. ConclusionsOur results greatly expanded the predicted number of coronaviruses proteins and identified potential viral peptide suggested to be involved in viral virulence. These methods and findings shed new light on coronavirus biology and provides a valuable resource for future genomic studies of coronaviruses.

Comparison of curriculum system of biomedical science in different universities / 中华医学教育探索杂志

Shanghai Jiao Tong University established the first biomedical science in China in 2016. Learning the successful experience from international universities can promote the development of this major. According to the comparison of cultivation program and curriculum system in different top universities at home and abroad, it was showed that Oxford University focused on the pluralism development of students, University of Technology Sydney paid attention to the combination of basis and clinical practice, and the University of Hong Kong stressed the integration of clinical practice, science and research, and transformation. Through the exploration of the details of educational system this university, we found that we mainly focused on five innovation ideas: building the basic knowledge, strengthening comprehensive basic knowledge teaching, stimulating students' interests towards biomedical science, developing their ability and promoting innovative education and training. Based on analysis of those cases, it is showed that the development of biomedical science in China should solve problems in curriculum integration and practical education of science and research, so as to achieve the goal to cultivate more talents in this major and boost the development and advances in the field of biomedical science.

Comparison of curriculum system of biomedical science in different universities / 中华医学教育探索杂志

Shanghai Jiao Tong University established the first biomedical science in China in 2016. Learning the successful experience from international universities can promote the development of this major. According to the comparison of cultivation program and curriculum system in different top universities at home and abroad, it was showed that Oxford University focused on the pluralism development of students, University of Technology Sydney paid attention to the combination of basis and clinical practice, and the University of Hong Kong stressed the integration of clinical practice, science and research, and transformation. Through the exploration of the details of educational system this university, we found that we mainly focused on five innovation ideas: building the basic knowledge , strengthening comprehensive basic knowledge teaching, stimulating students' interests towards biomedical science, developing their ability and promoting innovative education and training . Based on analysis of those cases , it is showed that the development of biomedical science in China should solve problems in curriculum integration and practical education of science and research , so as to achieve the goal to cultivate more talents in this major and boost the development and advances in the field of biomedical science.

Isolation and characterization of bacteriophage against extended-spectrumβ-lactamase-producing Escherichia coli strains / 上海交通大学学报（医学版）

Objective · To isolate phages which can fight against extended-spectrum β-lactamase (ESBLs)-producing Escherichia coli (E. coli), and provide basic research for establishment of E. coli phage library and treatment of bacterial infection. Methods · Samples collected from sewage were co-cultured with 93 ESBLs-producing E. coli strains. A phage named JDEC001 was isolated by double agar overlay plaque assay. The biological characteristics, complete genome sequence and comparative genome analyses of JDEC001 were studied respectively. Results · JDEC001 belongs to the lytic phage as a member of the Caudovirales order, Podoviridae family. It has high activity at pH from 5 to 11 and with temperature from 0 to 39 ℃ .Whole-genome sequencing of JDEC001 demonstrated double-stranded DNA genome of 38745 bp with GC content of 49.93%, which encoded 46 open reading frames. The comparative genomics also showed that there was no virulent genes or antibiotic resistant genes in its genome. Conclusion · The phage JDEC001 against ESBLs-producing E. coli was isolated and purified, with good stability in a broad range of pH and temperature.

Characterization of bacteriophage vB_AbaP_PD-AB9 infecting Acinetobacter baumannii with broad host range / 中华检验医学杂志

Objective To isolate bacteriophages against extensively-drug resistant Acinetobacter baumannii from hospital sewage and analyze their biological characteristics.Methods Extensively-drug resistant Acinetobacter baumannii isolated from several hospitals in Shanghai during December, 2013 to July, 2014 were used as host bacteria, adopting double-layer agar method to isolate bacteriophages from raw sewage of these hospitals.The phage with broad host range was selected for further study, including observation of electron microscopic morphology, examination of thermal stability, pH stability and the optimal MOI, drawing of the adsorption, one-step-growth and infection curves, as well as sequencing of the phage genome DNA. Results An extensively-drug resistant Acinetobacter baumannii bacteriophage vB_AbaP_PD-AB9 ( PD-AB9 for short) with broad host range was isolated, and electron microscopy revealed it belonged to Podoviridae family.The optimal MOI of PD-AB9 was 0.001.PD-AB9 remained stable among 4 ℃to 50 ℃and pH 4 to 11.In the adsorption experiment, the adsorption rate of PD-AB9 reached above 95%within 5 min.PD-AB9 had a latent period of 4 min and a burst size of 213.PD-AB9 could obviously restrain the host growth, with faster effect at the higher MOIs (MOI=1, 0.1, 0.01) than at the lower ones (MOI=0.001, 0.000 1).Furthermore, genome of PD-AB9 proved to be a double-stranded linear DNA with size of 40 938 bp and GC content of 39.34%.Conclusions PD-AB9 exhibits good thermal stability, wide pH tolerance range, very fast adsorption, a short latent period, a large burst size and it could quickly cause effective host lysis after infection.Therefore, PD-AB9 is promised to act as a new antimicrobial agent to control drug-resistant Acinetobacter baumannii infections and its bio information remains to be further studied.

Inhibition role of fusing antimicrobial peptides humanβ-defensin 3 and carbohydrate binding domain on staphylococcus / 国际检验医学杂志

Objective To explore the inhibition of fusing antimicrobial peptides humanβ-defensin 3 and carbohydrate binding do-main on Staphylococcus aureus N315 and Staphylococcus epidermidis 35984.Methods The direct bactericidal test and other molec-ular biology methods were adopted to detect the inhibition role on Staphylococcus aureus strain N315 and Staphylococcus epidermi-dis strain 35984 and the influence on the key genes expression.Results The direct bactericidal test demonstrated that antimicrobial peptides hBD3 and hBD3-CBD had significantly inhibitory effects on staphylococcus aureus N315 and staphylococcus epidermidis 35984;the inhibitory effects of hBD3-CBD was stronger than that of hBD3;the stability of the inhibitory effects of hBD3-CBD also stronger than that of hBD3.In the key gene expression test,there were significant inhibitions on the agr and mecA gene expressions in Staphylococcus aureus N315 and Staphylococcus epidermidis 35984 by hBD3-CBD.At the same time,hBD3-CBD could inhibit the icaA gene expression and promote icaR gene expression in Staphylococcus epidermidis 35984,which indicated that hBD3-CBD could inhibit the biofilm formation of Staphylococcus epidermidis.Conclusion The fusion strategy of antimicrobial peptide has very important significance for improving the antibacterial efficacy of antimicrobial peptides and brings more hope in their future applications.

High prevalence of pathogenic Leptospira in wild and domesticated animals in an endemic area of China.

OBJECTIVE: To assess the prevalence of Leptospira detected in wildlife and domesticated animals in Jiangxi Province, China, in. METHODS: Urine samples from 28 buffaloes and kidney samples from 50 pigs, 50 dogs and 38 rats were collected from Fuliang and Shangrao County, Jiangxi Province, China, in October 2009. Polymerase chain reaction(PCR)and culture analyses were used to detect Leptospira. The cultured isolates were typed using the microscopic agglutination test(MAT). RESULTS: The results showed that rats potentially serve as the main reservoir of leptospiral infection, followed by dogs. Although 16% of rats (6/38) were positive using culture analysis, PCR analysis using the diagnostic primers G1/G2 and B64I/B64II or lipL32 showed identification as 50% and 24%, respectively, of the rat samples as positive for the presence of leptospiral DNA. CONCLUSIONS: PCR-based detection of leptospiral DNA in infected kidney tissues of reservoirs is more efficient when using G1/G2 primers than lipL32 primers. However, the latter primers have a potential application for detection in urine samples. The alarmingly high prevalence of leptospiral DNA in the wild rat population near human habitation underscores the utility of routine Leptospira surveillance, preferably using PCR methods, which are more sensitive than traditional culture-based methods.

Research progress of role of innate immunity in infection of leptospira / 上海交通大学学报（医学版）

Leptospirosis is an important zoonosis with worldwide distribution. As the first procedure in immunity system, the role and significance of innate immunity in controlling infection at the early stage of the disease have gradually been emphasized. Macrophages can phagocytize and kill leptospira, while the pathogenic leptospira can evade the killing by macrophages. In addition, neutrophils, complement system and cytokines also contribute to the defence of leptospira infection.

A novel pore-forming hemolysin protein in Leptospira species / 中国人兽共患病学报

Hemolysins of Leptospira interragans have been shown to be the virulence factor in the pathogenesis of leptospirosis and 10 potential hemolysin genes were charecterized by genomic annotation of L.interrogans serovar.Lai strain 56601. In the present study, the LA0202 gene supposed to encode one of the new potential hemolysin was cloned and the protein encoded was purified. The purified protein was shown to have highly hemolytic activity as demonstrated on the sheep blood agar plate. It was also confirmed that the LA0202 protein-mediated hemolysis on sheep erythrocytes was osmotically protected by PEG6000. Meanwhile, this protein could induce pore formation on sheep erythrocytes and cause damages on the membrane of human L-02 liver cells. In addition, it could induce apoptosis of human L-02 liver cells after treatment of cells with this protein for 24 hours. It is evident that LA0202 protein acting as a pore-formong hemolysin can induce cytotoxic damage on mammalian cells.

Mechanisms of phagocytosis of Leptospira by peritoneal macrophages of guinea pigs / 上海交通大学学报（医学版）

Objective To investigate the mechanisms of phagocytosis of virulent Leptospira by peritoneal macrophages of guinea pigs,andevaluatetheroleof innateimmuneinthepathogenesisof leptospirosis. Methods Peritoneal macrophages of guinea pigs were extracted. Three specific inhibitors ( microfilament inhibitor cytochalasin D,microtube inhibitor colchicine and PI3K signalling pathway inhibitor LY294002) were added respectively to the macrophages 1 h before the infection of virulent Leptospira interrogans serovar Lai type strain Lai in vitro.Meanwhile, control group without inhibitor was established.Phagocytosis was observed by laser scanning confocal microscopy and phagocytic rates were evaluated by flow cytometry 3 h after infection.ResultsThe phagocytic rates of control group, cytochalasin D group, colchicine group and LY294002 group were (38.98 ± 0.91)%,(23. 99 ± 1. 40) % ,(40.81±0.91)% and (39.64 ±3.56) %, respectively.The phagocytic rate of cytochalasin D group was significantly lower than that of control group (P < 0. 05), while those of colchicine group and LY294002 group were not significantly different from that of control group (P >0.05). ConclusionMicrofilaments play an important role in the phagocytosis of strain Lai by peritoneal macrophages,but the process is independent on PI3K signalling pathway,and microtubes play little part during the phagocytosis.

The immune responses induced by a recombinant DNA vaccine for leptospirosis:pVAX1/LipL21-LipL32 / 中国人兽共患病学报

Two highly conserved and with abundant quantity of lipoproteins in outer membrane of pathogenic species,but not in saprophytic species of leptospira ,LipL32 and LipL21,were selected to construct the fusion gene DNA vaccine pVAX1/LipL21-LipL32,and its ability to induce immune responses in BALB/c mice inoculated with this recombinant DNA vaccine was investigated in the present study.Expression of the fusion-protein LiPL21-LiPL32 was demonstrated in HEK293 cells following transfection with the fusion gene DNA vaccine and the immune responses induced after intramuscular inoculation with this DNA vaccine in BALB/c mice was then evaluated by microscopic agglutination test (MAT),meanwhile the ELISA assay was used to detect the cytokines induced.It was demonstrated that significant level of specific antibodies agglutinating antigens of Leptospira interrogans could be detected by MAT after DNA vaccine inoculation.The production of cytokines IL-10 and TNF-β in mice inoculated with DNA vaccine pVAX1/LipL21-LipL32 was significantly increased in comparison with that of the group inoculated with pVAX1 alone.These results indicate that the recombinant DNA vaccine pVAX1/LipL21-LipL32 may be of potential value to design and develop new generation of vaccines against leptospirosis.

Up-dated information on the virulence of community-associated methicillin-resistant Staphylococcus aurues / 基础医学与临床

Since the emergence in 1980s,community-associated methicillin-resistant Staphylococcus Aurues (CA-MRSA) has caught great attention of the researchers and clinical practitioners all over the world. In recent scientific papers,people found that CA-MRSA's capability to adapt itself to the hostile environment and to colonize is a kind of important virulence factor. A newly unveiled gene,designated arginine catabolic mobile element (ACME),in USA300 stains contributes much to this sort of ability. The arginine deiminase encoded by ACME plays an important role in colonization.

Apoptosis in sepsis / 中国病理生理杂志

Immune cells that undergo increased apoptosis include lymphocytes and macrophages,yet the apoptosis of neutrophils is decreased in sepsis.Increase in apoptosis has also been reported in non-immune cells such as gastrointestinal cells,epithelial cells of lung as well as endothelial cells.The altered apoptotic cell death may contribute to the initiation and aggravation of immune and organ dysfunction in sepsis.Elucidating the changes and mechanism of apoptosis and taking measures to control apoptosis may be an effective strategy for the treatment of sepsis.