Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective:Given the high incidence and mortality rate of sepsis,early identification of high-risk patients and timely intervention are crucial.However,existing mortality risk prediction models still have shortcomings in terms of operation,applicability,and evaluation on long-term prognosis.This study aims to investigate the risk factors for death in patients with sepsis,and to construct the prediction model of short-term and long-term mortality risk. Methods:Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV(MIMIC-IV)database and randomly divided into a modeling group and a validation group at a ratio of 7?3.Baseline data of patients were analyzed.Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model.The time-dependent area under the curve(AUC),calibration curve,and decision curve were used to evaluate the differentiation,calibration,and clinical practicability of the model. Results:A total of 14 240 patients with sepsis were included in our study.The 28-day and 1-year mortality were 21.45%(3 054 cases)and 36.50%(5 198 cases),respectively.Advanced age,female,high sepsis-related organ failure assessment(SOFA)score,high simplified acute physiology score II(SAPS II),rapid heart rate,rapid respiratory rate,septic shock,congestive heart failure,chronic obstructive pulmonary disease,liver disease,kidney disease,diabetes,malignant tumor,high white blood cell count(WBC),long prothrombin time(PT),and high serum creatinine(SCr)levels were all risk factors for sepsis death(all P<0.05).Eight variables,including PT,respiratory rate,body temperature,malignant tumor,liver disease,septic shock,SAPS II,and age were used to construct the model.The AUCs for 28-day and 1-year survival were 0.717(95%CI 0.710 to 0.724)and 0.716(95%CI 0.707 to 0.725),respectively.The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. Conclusion:The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

Objective:To investigate the prevalence of enterovirus 71 (EV71) and the genetic characteristics of VP1 region in common hand, foot and mouth disease (HFMD) cases in Shenzhen from 2016 to 2022.Methods:Throat swabs from mild HFMD in Shenzhen sentinel hospitals were collected from 2016 to 2022. A total of 38 EV71-positive samples were screened from these throat swabs and were sequenced. Then, the VP1 sequence of these EV71-positive samples were analyzed for their phylogenetic evolution by bioimformatics software DNAStar and MEGA 6.Results:From 2016 to 2022, the number of EV71 infections among HFMD patients in Shenzhen sentinel hospitals decreased from 136 in 2016 to 0 in 2022. The mumber of EV71 infections in 2018 and 2019 decreased by 96.3%(257/267) compared to that in 2016 and 2017. From 2020 to 2022, the number of EV71 infections decreased to 0. During this period, the EV71 vaccination rate among HFMD patients increased from 6.4% to 39.6%; Evolutionary analysis showed that the nucleotide homology and amino acid homology between 38 EV71 sample strains in Shenzhen from 2016 to 2022 were 91.8%-99.9% and 98.3%-100.0%, all belonging to the C4a subgenotype; Among them, 26 strains wene local epidemic strains, and 11 strains were imported from other provinces, with a close genetic relationship with epidemic strains in Hainan, Yunnan, Sichuan, Tianjin, Henan, Jilin, and other places. One strain from 2017 had the closest genetic relationship with the US epidemic strain OP207969-USA-2017. Further comparing the EV71 epidemic strains in Shenzhen from 2016 to 2022 and EV71 severe strains, it was found that the EV71 strains in Shenzhen carried four amino acid mutation sites related to severe condition, named R22H, K43R, I249V and T289A.Conclusions:The EV71 epidemic strains in Shenzhen from 2016 to 2022 all belong to the C4a subgenotype, and the number of EV71 infection shows a downward trend with the increase of vaccine coverage rate. At the same time, the distribution of EV71 virus strains in Shenzhen shows a significant decrease in local strains and a predominance of imported strains. There are a total of four amino acid mutation sites associated with severe cases in the EV71 sample strains in Shenzhen from 2016 to 2022. Among them, 22R and 289T are located at the N and C ends of VP1, which are related to EV71 adsorption and targeting cells. The 43R site is associated with binding ability to Annexin2 protein, which enhances cell binding ability.

Objective To analyze the genetic characteristics of VP1-VP4 genes carried by cox-sackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015. -ethods The VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6. 0 and MEGA6. 02 software packages. Results Four cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98. 8％-98. 9％ homology in nucleotide sequences and 99. 3％-99. 8％ in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95. 0％ homology in nucleotide sequences and 99. 3％ homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785). Conclusions All CVA6 strains causing severe HFMD ca-ses in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.

Objective: To investigate the genetic characteristics of VP1 genes carried by coxsackievirus A16 strains isolated from cases of hand foot and mouth disease (HFMD) in Shenzhen during 2016 to 2017. Methods: Fecal and anal swab specimens were collected from patients with mild HFMD in four sentinel hospitals and the Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, China during 2016 to 2017. All specimens were tested for CVA16 viral RNA using real-time RT-PCR. The VP1 genes of 51 randomly selected CVA16 strains were amplified by RT-PCR and then sequenced using TaKaRa Biomedical Technology (Dalian). Bioinformatics software, including Mega6.02, BioEdit and DNAStar, was used for comparison and analysis of the VP1 genes. Results: CVA16 strains in Shenzhen during 2016 to 2017 mainly belonged to B1a and B1b subtypes as well as an emerging subtype B3. The epidemic of B1b subtype was found in both 2016 (28 strains) and 2017 (19 strains), while the B1a subtype (two strains) was only detected in 2017. Two B3 subtype strains were detected in 2017. The strains of B1b subtype were closely related to the strains isolated in Shanghai (JQ314149), Wenzhou (KP289416) and Beijing (KU254598), while the B1a subtype strains were closely related to the strains isolated in Kunming (JQ316639) and Tailand (GQ184139). The B3 subtype strain was an emerging CVA16 epidemic strain in mainland China. Further comparison of the CVA16 epidemic strains in Shenzhen area during 2016 to 2017 with the CVA16 strains causing severe neurological symptoms showed that two amino acid mutations (S14N and M23L) were found in VP1 protein. Conclusions The epidemic strains of CVA16 were B1b subtype in Shenzhen area in 2016. However, B1a, B1b and the emerging B3 subtype strains were prevalent in 2017. Compared with the CVA16 strains causing severe neurological symptoms, the CVA16 strains circulating in Shenzhen during 2016 to 2017 carried two amino acid mutations inVP1 protein.

Objective To evaluate the clinical capability of young general practitioners (GPs) in communities in Shanghai.Methods A cross-sectional survey on clinical ability of young GPs was adopted from October to December 2014.Total 211 GPs aged (31 ± 2) years (25-35) from 17 districts of Shanghai participated in the study.Written examination and objective structured clinical examination (OSCE) was applied in the evaluation.Results All 211 GPs (63 male and 148 females) completed the assessment.The overall score of the assessment was (602 ± 83) and the pass rate was 62.6％ (132/211).In written examination the average score was (64 ±7) and the pass rate was 72.1％ (152/211).In OSCE,the highest score (80 ± 15) and pass rate (92.9％,196/211) was in CPR skill,followed by communication skill [average score:(76 ± 15) and pass rate:85.8％ (181/211)].The lowest average score was physical examination (47 ± 15) with a pass rate of 26.1％ (55/211),followed by electrocardiogram reading [average score:(84 ±31) and pass rate:39.8％ (84/211)].In basic operation station,the lowest score was using funduscope and gynecologial examination (29.8％ and 45.4％,respectively).Conclusion Young GPs in Shanghai communities basically master clinical skills,but also have some deficiencies,the training in certain skills need to be strengthened.

Objective To analyze the VP1-VP4 genetic region of enterovirus 71 ( EV71 ) strains isolated from children with severe or mild hand, foot and mouth disease ( HFMD) in Shenzhen in 2012. Methods EV71 strains were isolated from five children with mild HFMD and five children with severe HFMD in Shenzhen in 2012.Reverse transcription-polymerase chain reaction ( RT-PCR) method was used to amplify the sequence of VP1-VP4 genes of EV71 strains.The sequences of the amplified products were analyzed by comparing with those of the EV71 reference strains ( A, B and C genotypes) published in Gen-Bank using nucleotide alignment, amino acid alignment and phylogenetic tree analysis.Results The homo-geneity between the EV71 strains isolated from severe and mild cases was 95.1%-98.2% in nucleotides and 99.2%-100% in amino acids.The VP1-VP4 nucleotide sequences of 5 strains isolated from severe cases and 5 strains from mild cases in Shenzhen shared 87.9%-97.8% homologies in nucleotides and 97.3%-99.9% homologies in amino acids with the genotype C EV71 reference strain.The EV71 strains isolated from children in Shenzhen were highly similar with the EV71 strain (FJ439769) isolated in Fuyang in 2008 and the one isolated in Jingdezhen in 2011 (JQ806378, C4a subtype) in nucleotide sequences.Mutations at the residue 31 in the VP1 region ( N→D ) were detected in 3 strains isolated from children with severe HFMD.Conclusion All of the 10 EV71 strains isolated in Shenzhen in 2012 belonged to the sub-genotype C4a.The mutation ( aa31 N→D) in the VP1 region of EV71 might be related to the different clinical mani-festations of HFMD cases in Shenzhen area.

Objective To assess community health service ability of general practitioners (GPs) with the Standardized General Practitioner Training(SGPT) in Shanghai.Methods One hundred and four GPs receiving SGPT and matched 102 GPs without SGPT were enrolled in this retrospective cohort study from September to November in 2014.Community health service ability,including abilities in basic medical service and public health service were assessed and compared between two groups.Written examination was applied in the public health services ability assessment.Objective structured clinical examination (OSCE) was applied for evaluation of basic medical service abilities.Results The scores of written examination in GPs with SGPT were higher than those without SGPT[(66 ±4) vs.(62 ±7),P ＜0.01].The OSCE scores in GP with SGPT were higher than those without SGPT [(494 ± 78) vs.(448 ± 80),P ＜ 0.01].GPs with SGPT also abtained the higher scores in consultation competence and clinical skills assessment [(245 ± 44) vs.(225 ±40),P＜0.01;(252 ±59) vs.(225 ±61),P ＜0.01].In OSCE,GPs with SGPT got higher score than those without SGPT in 5 stations (medical history collection,doctor-patient communication,basic operation,ECG interpretation,and CPR) (all P ＜ 0.01);however,no significant differences were observed in 3 stations (physical examination,case analysis and X-ray interpretation) between two groups (all P ＞ 0.05).Conclusions GPs with SGPT have better basic medical service and public health service ability.But some aspects of basic medical service ability need to be strengthened in the training and practice.

Objective To survey the current working status of general practitioners (GPs) who received residency training in Shanghai.Methods The current status of general practitioners,who completed residency training in Shanghai from 2013 to 2014,was surveyed with self-designed questionnaire by e-mail.The survey items included current employers,job specification,clinical practice,teaching,scientific research and so on.Results Three hundred and thirteen out of 377 GPs,who completed residency training from 2007 to 2012,participated in the survey (83.0％),including 85 males and 228 females with a mean age of (31.2 ± 2.6) years.Among all participants,298 (95.2％) worked in community health service centers,12.8％ (40/313) of them were involved in general practice teaching,9.9％ (31/313) undertook management,9.3％ (29/313) did academic research in community,and 7.7％ (24/313) had chance for overseas study.The survey also showed that 134 person/times received various commendations and awards.Conclusion Most GPs who completed residency training are undertaking clinical practice in community health service centers,and they are also well involved in management,teaching,and research.