Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.@*METHODS@#Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.@*RESULTS@#A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.@*CONCLUSION@#Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Transcriptomic analysis of the ΔPaLoc mutant of Clostridioides difficile and verification of its toxicity / 中华预防医学杂志

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.

Epidemiological and etiological characteristics of Vibrio parahaemolyticus strains causing foodborne disease outbreaks in Guangdong Province from 2017 to 2020 / 中华预防医学杂志

Objective: To study the epidemiological and pathogenic characteristics of Vibrio parahaemolyticus isolated from outbreaks cases in Guangdong Province, 2017-2020. Methods: Epidemiological characteristics of 87 outbreak events caused by Vibrio parahaemolyticus were analyzed. Strains were serotyped, and then analyzed by pulsed-field gel electrophoresis (PFGE). Results: The food-borne disease outbreak caused by Vibrio parahaemolyticus was found in 16 cities. 44.8% (39/87) and 37.9% (33/87) of the outbreaks occurred in hotels, restaurants and school canteens, respectively. Improper food processing and storage (40.2%, 35/87) and cross contamination caused by indiscriminate raw and cooked food (25.3%, 22/87) were the main causes of food-borne disease outbreaks of Vibrio parahaemolyticus. The main serotypes of patient derived strains were O3:K6 (87.5%) and O4:KUT (22.5%). The similarity value between O3:K6 type isolates was 65.5%-100.0%, and the PFGE pattern similarity value of O4:KUT type isolates was 66.5%-100.0%. Conclusion: Outbreaks caused by Vibrio parahaemolyticus are widely distributed in Guangdong province. It is necessary to strengthen the publicity and education on the correct handling of food in hotels, restaurants, schools, and unit canteens. O3:K6 and O4:KUT serotypes are the main serotypes of the outbreak. There is genetic diversity among the epidemic strains.

Identification and analysis of 2 Corynebacterium diphtheria strains in Guangdong Province / 中华预防医学杂志

Objective: To identify and analyze two strains of C. diphtheriae in Guangdong Province by combining whole genome sequencing with traditional detection methods. Methods: The C. diphtheriae was isolated from Guangzhou in 2010 and Zhuhai in 2020 respectively. Isolates were identified by API Coryne strips and MALDI-TOF-MS. Genomic DNA was sequenced by using Illumina. The assembly was performed for each strain using CLC software. J Species WS online tool was used for average nucleoside homology identification, then narKGHIJ and tox gene were detected by NCBI online analysis tool BLSATN. MEGA-X was used to build a wgSNP phylogenetic tree. Results: GD-Guangzhou-2010 was Belfanti and GD-Zuhai-2020 was Gravis. ANIb between GD-Guangzhou-2010 and C. belfantii was 99.61%. ANI between GD-Zhuhai-2020 and C. diphtheriae was 97.64%. BLASTN results showed that the nitrate reduction gene narKGHIJ and tox gene of GD-Guangzhou-2010 was negative, while GD-Zhuhai-2020 nitrate reduction gene narKGHIJ was positive. There were two obvious clades in wgSNP phylogenetic tree. The first clades included all Mitis and Gravis types strains as well as GD-Zhuhai-2020. The second clades contained all isolates of C.belfantii, C.diphtheriae subsp. lausannense and GD-guangzhou-2010. Conclusion: Two non-toxic C. diphtheriae strains are successfully isolated and identified. The phylogenetic tree suggests that GD-Guangzhou-2010 and GD-Zhuhai-2020 are located in two different evolutionary branches.

Structural and functional characterizations of altered infectivity and immune evasion of SARS-CoV-2 Omicron variant

The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an "active" conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

Genomic Evolution and Variation of SARS-CoV-2 in the Early Phase of COVID-19 Pandemic in Guangdong Province, China.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) with unknown origin spread rapidly to 222 countries, areas or territories. To investigate the genomic evolution and variation in the early phase of COVID-19 pandemic in Guangdong, 60 specimens of SARS-CoV-2 were used to perform whole genome sequencing, and genomics, amino acid variation and Spike protein structure modeling analyses. Phylogenetic analysis suggested that the early variation in the SARS-CoV-2 genome was still intra-species, with no evolution to other coronaviruses. There were one to seven nucleotide variations (SNVs) in each genome and all SNVs were distributed in various fragments of the genome. The Spike protein bound with human receptor, an amino acid salt bridge and a potential furin cleavage site were found in the SARS-CoV-2 using molecular modeling. Our study clarified the characteristics of SARS-CoV-2 genomic evolution, variation and Spike protein structure in the early phase of local cases in Guangdong, which provided reference for generating prevention and control strategies and tracing the source of new outbreaks.

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI

A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2

Mutations and transient conformational movements of receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable, present immune escape routes to SARS-CoV-2. To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, combination of RBD-targeting NAbs and NTD-binding NAb, FC05, dramatically enhanced the neutralization potency in cell-based assays and animal model. Results of competitive SPR assays and cryo-EM structures of Fabs bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in NTD and RBD of S, when immunized in rabbits elicited potent protective immune responses against SARS-CoV-2. These results provide a proof-of-concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD. One sentence summaryImmunogens identified in the NTD and RBD of the SARS-CoV-2 spike protein using a cocktail of non-competing NAbs when injected in rabbits elicited a potent protective immune response against SARS-CoV-2.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

Reassessment of Echocardiography for Diagnosing Infectious Endocarditis / 中国循环杂志

Objective:To explore the value of echocardiography for diagnosing infectious endocarditis (IE).Methods:A total of 487 patients with cardiovascular implantable electronic devices (CIED) infection treated in our hospital from 2013-01 to 2015-06 were enrolled.Based on symptoms,blood culture and echocardiography,9 patients with suspected IE were further examined by 18F-FDG PET-CT to confirm their diagnosis and classification.Definitive therapy was conducted and the patients were followed-up for 1 year to confirm the diagnostic accuracy of echocardiography on CIED induced IE.Results:3 patients were preliminarily diagnosed for bacteremia since no vegetation was found by echocardiography,while IE was finally diagnosed by PET-CT.2 patients were preliminarily diagnosed for IE by echocardiography presented valvular vegetation,while PET-CT showed no evidence of vegetation;then one of them was diagnosed as bacteremia by positive blood culture and another was diagnosed as non-infection.4 patients were preliminarily diagnosed for IE by echocardiography indicated existing vegetation after CIED lead extraction,while PET-CT demonstrated no infection sign in heart chamber and the finally diagnosed was as "non-infectious fibrous residual tissue".According to final diagnosis,definitive therapies were performed to specific patients with at least 1 year follow-up study,no one had new and recurrent infection.Conclusion:Echocardiography had deficiency for diagnosing vegetation in heart chamber especially in suspicious IE patients after CIED lead extraction.It is necessary to make accurate diagnosis with other method for guiding appropriate therapy.

Suspected pathogen detection and epidemiological analysis of hand, foot and mouth disease in Minhang District of Shanghai from 2009 to 2016 / 复旦学报（医学版）

Objective To investigate the etiological agents of the outbreak of hand,foot and mouth disease (HFMD) in Minhang District of Shanghai from 2009 to 2016,and to provide evidence for the prevention and management policy of HFMD by collecting suspected HFMD samples for laboratory testing from HFMD sentinel hospitals,the Children's Hospitals of Fudan University and jurisdiction community health service centers.Methods Specimens including stools,throat swabs and anal swabs were collected from patients suspected of HFMD from surveillance hospitals,i.e.,Children's Hospital of Fudan University and jurisdiction community health service centers during 2009 and 2016.The specimens were detected by real-time RT-PCR with the five types of viruses including panenterovirus (EV),enterovirus 71 (EV71),Coxsackie virus A16 (CVA16),Coxsackie virus A6 (CVA6) and Coxsackie virus A10 (CVA10).The distribution characteristics of pathogens were analyzed.Results During 2009 and 2016 we collected 3 744 cases of HFMD,the positive detection rate of pan-enterovirus were 84.83％ (3 176 cases),including EV71 (64.45％) and CVA16 (15.77％),then were CVA6 (9.23％) and other EV (8.78％),and CVA10 was only 0.76％.The major etiological agent was EV71.The advantage of different years and different season strain presented dynamic change,mainly EV71 and CVA16 co-popular in 2009,mainly EV71 epidemic from 2010 to 2011,EV71 and CVA16 were co-popular again in 2012,and the priority was EV71,then EV71 and other EV were co-popular in 2013.After 2014,CVA6 gradually increased,mainly CVA6 was popular 2015 and 2016,especially in 2016,the proportion of CVA6 ranged as high as 40.55％.CVA10 showed sporadic distribution trend in very low proportion.From the difference of age and gender in HFMD cases,the males were more than the females (1.68 ∶ 1),and the incidence was the highest in children of 1-3 years old.The peak of incidence occured in April to July,then in September to November.Conclusions HFMD onset seasons mainly were summer and fall-and-winter in bimodal popular models.It happens in children under 5 years of age.The incidence was higher in male than in female.The advantage of different years and different season strains present dynamic change,and the prevalence has obvious age and season limit.

Pathogenic surveillance of viral diarrhea in Minhang District of Shanghai from 2014 to 2016 / 复旦学报（医学版）

Objective To investigate the epidemiological and pathogenic characteristics of viral diarrhea in Minhang District of Shanghai.Methods Random sampling on diarrhea was conducted in intestinal outpatient departments of 2 sentinel hospitals according to a certain sampling interval in Minhang District from 2014 to 2016.Real-time PCR was used to detect rotavirus (RV),norovirus (NV),adenovirus (AD),astrovirus (AstV) and sapovirus (SaV) in fecal samples.Results A total of 11 243 cases of diarrhea were monitored in 2 sentinel hospitals during 2014 and 2016,with 3 213,3 600 and 4 430 cases for each year,respectively.Out of 809 stool specimens,309 were tested positively,and the positive rate was 38.48％.All 5 pathogenic viruses were detected,mostly NV (207 cases,66.99％)followed by RV (77 cases,24.92％).Conclusions NV accounted for the majority of reported infection diarrhea cases in Minhang District of Shanghai from 2014 to 2016,with significant seasonal peaks.Tailored prevention and control measures should be carried out,particularly in risk seasons.

Influenza surveillance in Minhang District of Shanghai from 2013 to 2016 / 复旦学报（医学版）

Objective To understand the epidemic characteristics of influenza in Minhang District of Shanghai during 2013-2016,so as to provide scientific basis for the prevention and control of influenza.Methods Surveillance data of influenza like illness (ILI) cases from the national influenza network and data of pathogen detection during 2013-2016 in Minhang District were selected to analyze the epidemic characteristics of influenza.Results The number of influenza like illness (ILI) was 37 738 from 2013 to 2016,which accounted for 0.90％ of the outpatients in monthly average.Meanwhile,4 094 samples were collected,among which 857 samples were virus positive.The total isolation rate was 20.93％.In 2013,the dominant strain was mainly seasonal influenza A (H3N2).Dominant strains of 2014 were influenza B (Yamagata) and seasonal influenza A (H3N2).In 2015,dominant strain was seasonal influenza A (H3N2) of summer peak,but the dominant strains of winter-spring peak were new type influenza H1N1 (H1N1 pdm09) and influenza B (Victoria) from December 2015 to April 2016.The dominant strain of winter peak in 2016 was seasonal influenza A (H3N2) popular.Spearman correlation analysis showed positive rate between ILI visiting rate (ILI％) and influenza virus (rs =0.460,P＜0.05).Conclusions The epidemic peaks of of influenza were winter-spring and summer in Minhang District,advantages strains were interaction pandemic with certain regulation.The characteristics of ILI visiting rate was coincident with influenza virus activity.

Rapid identification for Mycobacterium fortuitum with RNA isothermal transcription-mediated amplification and real-time detection assay / 中国人兽共患病学报

The aim of the study is to establish and evaluate a RNA isothermal transcription-mediated amplification and realtime detection assay (RIARD-MF) for the identification of Mycobacterium fortuitum in clinical isolates.RNA probes and specific primers of reverse transcription and amplification for T7 promoter were designed based on the sequence of M.fortuitum 16S rRNA.The isothermal successive cycles of amplification were performed for real-time detection by using T7 RNA polymerase at 42 ℃.Five non-mycobacterium strains,20 Mycobacterium strains and 259 clinical strains were detected by the established assay to evaluate the specificity and sensitivity,and the results were compared with those of PCR sequencing.In the test of 5 non-mycobacterium strains and 20 Mycobacterium strains,only M.fortuitum was positive,and the remaining 24 strains of bacteria were negative,which was consistent with PCR gene sequencing.The sensitivity and specificity of RIARD-MF reached 60 CFU/mL and 100％.In the test of 259 strains of clinical isolates,5 strains were identified to be M.fortuitum,the remaining 254 strains were not identified to be M.Fortuitum,which was also consistent with PCR gene sequencing.Both the specificity and sensitivity reached up to 100％ in the detection of clinical isolates.It suggested that the RIAR-DMF established in this study is a specific,sensitive,accurate and rapid method for the identification of M.Fortuitum and it may be hopeful for rapid identification of M.fortuitum in clinical isolates.

Rapid identification for Mycobacterium fortuitum with RNA isothermal transcription-mediated amplification and real-time detection assay / 中国人兽共患病学报

The aim of the study is to establish and evaluate a RNA isothermal transcription-mediated amplification and realtime detection assay (RIARD-MF) for the identification of Mycobacterium fortuitum in clinical isolates.RNA probes and specific primers of reverse transcription and amplification for T7 promoter were designed based on the sequence of M.fortuitum 16S rRNA.The isothermal successive cycles of amplification were performed for real-time detection by using T7 RNA polymerase at 42 ℃.Five non-mycobacterium strains,20 Mycobacterium strains and 259 clinical strains were detected by the established assay to evaluate the specificity and sensitivity,and the results were compared with those of PCR sequencing.In the test of 5 non-mycobacterium strains and 20 Mycobacterium strains,only M.fortuitum was positive,and the remaining 24 strains of bacteria were negative,which was consistent with PCR gene sequencing.The sensitivity and specificity of RIARD-MF reached 60 CFU/mL and 100％.In the test of 259 strains of clinical isolates,5 strains were identified to be M.fortuitum,the remaining 254 strains were not identified to be M.Fortuitum,which was also consistent with PCR gene sequencing.Both the specificity and sensitivity reached up to 100％ in the detection of clinical isolates.It suggested that the RIAR-DMF established in this study is a specific,sensitive,accurate and rapid method for the identification of M.Fortuitum and it may be hopeful for rapid identification of M.fortuitum in clinical isolates.

Reassessment of Echocardiography for Diagnosing Infectious Endocarditis / 中国循环杂志

Objective:To explore the value of echocardiography for diagnosing infectious endocarditis (IE).Methods:A total of 487 patients with cardiovascular implantable electronic devices (CIED) infection treated in our hospital from 2013-01 to 2015-06 were enrolled.Based on symptoms,blood culture and echocardiography,9 patients with suspected IE were further examined by 18F-FDG PET-CT to confirm their diagnosis and classification.Definitive therapy was conducted and the patients were followed-up for 1 year to confirm the diagnostic accuracy of echocardiography on CIED induced IE.Results:3 patients were preliminarily diagnosed for bacteremia since no vegetation was found by echocardiography,while IE was finally diagnosed by PET-CT.2 patients were preliminarily diagnosed for IE by echocardiography presented valvular vegetation,while PET-CT showed no evidence of vegetation;then one of them was diagnosed as bacteremia by positive blood culture and another was diagnosed as non-infection.4 patients were preliminarily diagnosed for IE by echocardiography indicated existing vegetation after CIED lead extraction,while PET-CT demonstrated no infection sign in heart chamber and the finally diagnosed was as "non-infectious fibrous residual tissue".According to final diagnosis,definitive therapies were performed to specific patients with at least 1 year follow-up study,no one had new and recurrent infection.Conclusion:Echocardiography had deficiency for diagnosing vegetation in heart chamber especially in suspicious IE patients after CIED lead extraction.It is necessary to make accurate diagnosis with other method for guiding appropriate therapy.

Suspected pathogen detection and epidemiological analysis of hand, foot and mouth disease in Minhang District of Shanghai from 2009 to 2016 / 复旦学报（医学版）

Objective To investigate the etiological agents of the outbreak of hand,foot and mouth disease (HFMD) in Minhang District of Shanghai from 2009 to 2016,and to provide evidence for the prevention and management policy of HFMD by collecting suspected HFMD samples for laboratory testing from HFMD sentinel hospitals,the Children's Hospitals of Fudan University and jurisdiction community health service centers.Methods Specimens including stools,throat swabs and anal swabs were collected from patients suspected of HFMD from surveillance hospitals,i.e.,Children's Hospital of Fudan University and jurisdiction community health service centers during 2009 and 2016.The specimens were detected by real-time RT-PCR with the five types of viruses including panenterovirus (EV),enterovirus 71 (EV71),Coxsackie virus A16 (CVA16),Coxsackie virus A6 (CVA6) and Coxsackie virus A10 (CVA10).The distribution characteristics of pathogens were analyzed.Results During 2009 and 2016 we collected 3 744 cases of HFMD,the positive detection rate of pan-enterovirus were 84.83％ (3 176 cases),including EV71 (64.45％) and CVA16 (15.77％),then were CVA6 (9.23％) and other EV (8.78％),and CVA10 was only 0.76％.The major etiological agent was EV71.The advantage of different years and different season strain presented dynamic change,mainly EV71 and CVA16 co-popular in 2009,mainly EV71 epidemic from 2010 to 2011,EV71 and CVA16 were co-popular again in 2012,and the priority was EV71,then EV71 and other EV were co-popular in 2013.After 2014,CVA6 gradually increased,mainly CVA6 was popular 2015 and 2016,especially in 2016,the proportion of CVA6 ranged as high as 40.55％.CVA10 showed sporadic distribution trend in very low proportion.From the difference of age and gender in HFMD cases,the males were more than the females (1.68 ∶ 1),and the incidence was the highest in children of 1-3 years old.The peak of incidence occured in April to July,then in September to November.Conclusions HFMD onset seasons mainly were summer and fall-and-winter in bimodal popular models.It happens in children under 5 years of age.The incidence was higher in male than in female.The advantage of different years and different season strains present dynamic change,and the prevalence has obvious age and season limit.

Pathogenic surveillance of viral diarrhea in Minhang District of Shanghai from 2014 to 2016 / 复旦学报（医学版）

Objective To investigate the epidemiological and pathogenic characteristics of viral diarrhea in Minhang District of Shanghai.Methods Random sampling on diarrhea was conducted in intestinal outpatient departments of 2 sentinel hospitals according to a certain sampling interval in Minhang District from 2014 to 2016.Real-time PCR was used to detect rotavirus (RV),norovirus (NV),adenovirus (AD),astrovirus (AstV) and sapovirus (SaV) in fecal samples.Results A total of 11 243 cases of diarrhea were monitored in 2 sentinel hospitals during 2014 and 2016,with 3 213,3 600 and 4 430 cases for each year,respectively.Out of 809 stool specimens,309 were tested positively,and the positive rate was 38.48％.All 5 pathogenic viruses were detected,mostly NV (207 cases,66.99％)followed by RV (77 cases,24.92％).Conclusions NV accounted for the majority of reported infection diarrhea cases in Minhang District of Shanghai from 2014 to 2016,with significant seasonal peaks.Tailored prevention and control measures should be carried out,particularly in risk seasons.

Influenza surveillance in Minhang District of Shanghai from 2013 to 2016 / 复旦学报（医学版）

Objective To understand the epidemic characteristics of influenza in Minhang District of Shanghai during 2013-2016,so as to provide scientific basis for the prevention and control of influenza.Methods Surveillance data of influenza like illness (ILI) cases from the national influenza network and data of pathogen detection during 2013-2016 in Minhang District were selected to analyze the epidemic characteristics of influenza.Results The number of influenza like illness (ILI) was 37 738 from 2013 to 2016,which accounted for 0.90％ of the outpatients in monthly average.Meanwhile,4 094 samples were collected,among which 857 samples were virus positive.The total isolation rate was 20.93％.In 2013,the dominant strain was mainly seasonal influenza A (H3N2).Dominant strains of 2014 were influenza B (Yamagata) and seasonal influenza A (H3N2).In 2015,dominant strain was seasonal influenza A (H3N2) of summer peak,but the dominant strains of winter-spring peak were new type influenza H1N1 (H1N1 pdm09) and influenza B (Victoria) from December 2015 to April 2016.The dominant strain of winter peak in 2016 was seasonal influenza A (H3N2) popular.Spearman correlation analysis showed positive rate between ILI visiting rate (ILI％) and influenza virus (rs =0.460,P＜0.05).Conclusions The epidemic peaks of of influenza were winter-spring and summer in Minhang District,advantages strains were interaction pandemic with certain regulation.The characteristics of ILI visiting rate was coincident with influenza virus activity.