BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03％of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24％(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.

Reporting guidelines are structured checklists for researchers to follow when reporting spe-cific types of studies.As researches conducted in real-world settings to address practical issues,implementa-tion research has stringent requirements for the replicability of result and the transparency of reporting,making its reporting guidelines particularly important.This paper systematically introduces the reporting guidelines in the field of implementation science,outlines their classification systems and scopes of applica-tion,and focuses on explaining the core characteristics and functions of five key reporting guidelines,inclu-ding the Standards for Reporting Implementation Studies(StaRI),Reporting guidelines for implementation and operational research,the Template for Intervention Description and Replication(TIDieR),the Frame-work for Reporting Adaptations and Modifications-Enhanced(FRAME),and recommendations for specifying and reporting implementation strategies.Furthermore,combined with the PEDALs research paradigm in im-plementation science,this paper further clarifies the specific application pathways for reporting guidelines and discusses directions for refinement,aiming to provide references for researchers to select appropriate reporting guidelines.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To understand the etiological surveillance and drug resistance characteristics of Legionella pneumophila (LP) from the aqueous environment of public places in Shanghai, from 2011 to 2020, and provide evidence for surveillance of the disease. Methods:Environmental water samples were systematically collected from public venues in urban and suburban districts of Shanghai for LP surveillance. All the identified LP isolates underwent a series of testings including serotyping, pulsed field gel electrophoresis (PFGE), sequence-based typing, and antimicrobial susceptibility testing. χ2 test or Cochran-Armitage trend tests were used for statistical analysis and for temporal resistance patterns. Results:Among 6 263 water samples, the LP-positive rate was 20.93% (1 311/6 263). The positivity rate decreased from 24.98% (287/1 149) in 2011-2012 to 20.02% (1 024/5 114) in 2013-2020 ( χ2=13.92, P<0.001), with the highest monthly positivity observed from June to August (23.79%, 745/3 132). A total of 1 365 LP strains were isolated, of which 912 were further characterized, including 10 serotypes, 149 PFGE patterns, and 33 sequence types (ST). The predominant serotype was Lp1 (86.84%, 792/912), and the dominant ST was ST752 (29.50%, 269/912). ST clustering revealed two major clonal groups CG1 and CG2, accounting for 91.12% (831/912) of the isolates. The 190 LPs involved in the drug sensitivity test showed three resistance profiles: azithromycin resistance (31.05%, 59/190), ciprofloxacin resistance (0.53%, 1/190) and azithromycin+ciprofloxacin resistance (0.53%, 1/190). Azithromycin-resistant strains were predominantly ST1 (64.41%, 38/59). The antimicrobial resistance rate showed a significant decline, from 48.65% (18/37) in 2011-2012 to 28.10% (43/153) in 2013-2020 ( χ2=9.38, P=0.002). Conclusions:Compared to from 2011 to 2012, both the positivity rate and antimicrobial resistance prevalence of LP in public aqueous environments of Shanghai exhibited an overall decline from 2013 to 2020. The predominant types of LP were serotype Lp1 and sequence type ST752, with notable high-level resistance to azithromycin. Measures as enhancing the enforcement of water safety regulations and prioritizing surveillance of azithromycin resistance in LP were recommended to mitigate public health risks.

Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03％of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24％(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.

Objective:To understand the etiological surveillance and drug resistance characteristics of Legionella pneumophila (LP) from the aqueous environment of public places in Shanghai, from 2011 to 2020, and provide evidence for surveillance of the disease. Methods:Environmental water samples were systematically collected from public venues in urban and suburban districts of Shanghai for LP surveillance. All the identified LP isolates underwent a series of testings including serotyping, pulsed field gel electrophoresis (PFGE), sequence-based typing, and antimicrobial susceptibility testing. χ2 test or Cochran-Armitage trend tests were used for statistical analysis and for temporal resistance patterns. Results:Among 6 263 water samples, the LP-positive rate was 20.93% (1 311/6 263). The positivity rate decreased from 24.98% (287/1 149) in 2011-2012 to 20.02% (1 024/5 114) in 2013-2020 ( χ2=13.92, P<0.001), with the highest monthly positivity observed from June to August (23.79%, 745/3 132). A total of 1 365 LP strains were isolated, of which 912 were further characterized, including 10 serotypes, 149 PFGE patterns, and 33 sequence types (ST). The predominant serotype was Lp1 (86.84%, 792/912), and the dominant ST was ST752 (29.50%, 269/912). ST clustering revealed two major clonal groups CG1 and CG2, accounting for 91.12% (831/912) of the isolates. The 190 LPs involved in the drug sensitivity test showed three resistance profiles: azithromycin resistance (31.05%, 59/190), ciprofloxacin resistance (0.53%, 1/190) and azithromycin+ciprofloxacin resistance (0.53%, 1/190). Azithromycin-resistant strains were predominantly ST1 (64.41%, 38/59). The antimicrobial resistance rate showed a significant decline, from 48.65% (18/37) in 2011-2012 to 28.10% (43/153) in 2013-2020 ( χ2=9.38, P=0.002). Conclusions:Compared to from 2011 to 2012, both the positivity rate and antimicrobial resistance prevalence of LP in public aqueous environments of Shanghai exhibited an overall decline from 2013 to 2020. The predominant types of LP were serotype Lp1 and sequence type ST752, with notable high-level resistance to azithromycin. Measures as enhancing the enforcement of water safety regulations and prioritizing surveillance of azithromycin resistance in LP were recommended to mitigate public health risks.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.