China's growing contribution to sepsis research from 1984 to 2014

Supplemental Digital Content is available in the text


Introduction
Sepsis, a syndrome with physiologic, pathologic, and biochemical abnormalities induced by infection, is a major public health concern with high morbidity, mortality, and cost. [1][2][3] It was first proposed and defined in the first Consensus Conference for Sepsis Definitions held by American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) in 1991, which marked a new era for mechanisms, diagnoses and treatments in sepsis research. [4] Up to now, countless specialists and researchers have devoted themselves to this field in order to get a better understanding in mechanism of sepsis and develop new methods for the diagnosis and treatment, and their research results all come to publications in the end. China, with the growth of the overall economy and scientific research strength, also make great achievements in sepsis research. But the global and China's development trend regarding sepsis has not been well studied yet.
Bibliometrics, a well-established research method in information science, is often used for statistical analysis in written publications. [5] This scientific and quantitative method of analysis cannot only provide quantitative information about research environment, but also evaluate the quality of research by citation analysis, through which we can characterize research progress, explore the impact of a discipline, predict the development of a field, and give guidance to clinical and basic research. [6,7] Much bibliometric research has been carried out and has made remarkable contributions to the development of modern medicine in the areas of primary care, [8] neurology, [9] respiratory medicine, [10] urology, [11] pathology, [12] and cancer. [13] This bibliometric study was aimed to analyze the global sepsis research trends and evaluate China's growing contribution to sepsis research by comparing the quantity and quality of sepsisrelated publications during the 1984 to 2014 periods.

Data collection
The text file data downloaded from WOS were imported into Microsoft Excel 2010, and then, 2 authors verified the data entry and collection. The final data were further manually analyzed in Microsoft Excel 2010. Bibliometric indicators, including the total publication number, total citation frequency, citation frequency per paper, h-index, [14,15] research types, research orientations, research organization, author's contribution, journal and funding support were extracted from the original data to quantitatively and qualitatively analyze the publications.

Statistical methods
Graph Pad Prism 5.0 software was used for most of the statistical analyses. Linear regression was used to calculate the coefficient of determination (r 2 ) and to determine any significant changes in trends between 1984 and 2014. P values (or Bonferroni corrected P values) less than .05 were considered significant.

Citation and h-index analysis.
According to the analysis of the WOS database, all articles related to sepsis had been cited 1,882,285 times since 1984 (1,811,154 times without selfcitations) and the rate of self-citation is 3.8%. The cited frequency per paper was 26.67 times. Sepsis papers from the USA were cited most frequently, with 959,168 total citations (50.96%) and 38.203 citations per paper during the past 31 years ( Fig   The top 20 most contributing authors published 3483 sepsis papers in total (4.94%). Among these 20 authors, 9 were from the USA, 3 were from the Netherlands, and 2 were from Belgium. Professor VINCENT JL, from Universite Libre Bruxelles was the most productive author and published 434 papers related to sepsis and had the highest citation frequency (37,774) and hindex (81) (Fig. 4B, Online Supplementary Appendix 4B, http:// links.lww.com/MD/B762).
Global sepsis articles were supported by 15,135 funding agencies. The top 10 most contributing funding agencies are listed in Fig. 4C. The National Institutes of Health (NIH) ranked first, which supported 1893 sepsis articles, with the highest citations (44,142) and h-index scores (80). NSFC was the second largest contributing funding agency, which supported 648 sepsis articles.

Citation and h-index analysis.
The total citation frequency of China's sepsis articles was 30,884 (1.64%), ranking fifteenth in the world. In China, the citation frequency per paper was 12.15 and the h-index was 59 ( Fig. 2A and B, Online Supplementary Appendix 2, http://links.lww.com/MD/B762).   The top 10 funding agencies that supported China's sepsis research are listed in Fig. 6B. NSFC supported the most Chinese sepsis articles (648, 25.49%), followed by 973 project (113, 4.45%). The NSFC was the main Chinese funding organization. The fund supplied 134.35 million RMB for sepsis research from 1986 to 2014, with an average annual growth rate 29.78% (r 2 = 0.48, P < .001) (Fig. 6C, Online Supplementary Appendix 6B, http://links.lww.com/MD/B762). The Second Military Medical University gained the largest amount of NSFC funding (15.29 million RMB), followed by Zhejiang University (15 million) and Chinese People's Liberation Army General Hospital (13.84 million) (Fig. 6D).

Discussion
Our present bibliometric study provided a comprehensive overview of the development of the scientific literature in global sepsis research and summarized the contribution of China over the last 3 decades by comparing the quality and quantity in sepsis research articles. Worldwide sepsis research had made a tremendous increase in volume in the last 3 decades. The USA led this field with the highest publications, citations, and h-index. Sepsis research in China had a notable trend of increase in a number of scientific publications. However, the quality of China's sepsis research remained relatively lower when compared with the fast-growing quantities. In subcategories of research, researchers had relatively higher output in basic research than in clinical investigations. The NIH contributed the most funding to global sepsis research, while the NSFC was the most dominating funder in China.
Great advances were observed in global sepsis research, with 224 publications in 1984 increasing to 5278 in 2014, especially after the first Consensus Conference for Sepsis Definition held by ACCP/SCCM in 1991. [4] This Consensus Conference firstly proposed the terms of sepsis, severe sepsis, and septic shock, and put forward specific definitions for them, which marked a new era for this field with an unprecedented growth rate of 273.41% in 1991. Thus, successfully hosting this conference in 1991 may be the underlying reason why there was a substantial increase in the publications on sepsis between 1990 and 1992. Another on-going positive growth in sepsis literature occurred after 2003 when the Surviving Sepsis Campaign launched its evidence-based guideline to improve sepsis outcomes. [16] In 2016, the third international consensus conference for sepsis and septic shock definitions provided new definition and diagnostic criteria for sepsis, which may cause great repercussions to sepsis research in the future. [2] Sepsis research in China developed slowly in the early stage, but erupted after 2001, reaching 576 articles in 2014, which ranked second in the world. The recent fast development of sepsis research in China can be mainly ascribed to: The unprecedented growth in their economy in the last 3 decades in China, which pushed sepsis research forward. Many bibliometric studies have confirmed the significant roles of the economy, science, and technology in the progress of other disciplines. [8][9][10]12,13] China has increased its scientific research investments year-by-year. Additionally, increased governmental funding agencies, such as the NSFC and the 973 project, have enhanced research productivity. Many Chinese experts come back with wellrecognized experience, advanced techniques and bring more international collaborations in sepsis diagnoses and therapies. The large population base in China is associated with a large number of patients to study, which may bring more resources to sepsis studies. However, there is still a large gap between China and other leading countries in terms of the citation frequency and h-index. The relatively lower quality of sepsis publications from China may be due to: China lacks highly influential leading researchers and research institutions to implement high quality sepsis research. In our analysis, there were no Chinese researchers or institutions that ranked in the global top 20 contributing authors and institutions. The immaturity of the research system and the lack of experience in high quality research may be caused by the relatively later initiation of sepsis research in China. Second, China also lacks top international journals. The most popular journal that published China's sepsis research was the Chinese Medical Journal (IF 0.957), which has much less impact than other sepsis related journals. Third, the journals with high IF are usually English-written, while for China, as a non-Englishspeaking country, there may difficulty in writing scientific papers in English.
The present study indicated that researchers in China have relatively better output in basic research than in clinical investigation, This could be mainly attributed to the rapid development of NSFC during the past decade, which has the widest coverage in China and principally supports basic scientific researches. [17] On the other hand, China lacks clinical cooperating platforms and well-developed big database and analysis system. The vast amount of clinical information and research resources in different hospitals are relatively independent, resulting in a difficulty in carrying out multicenters clinical studies. Nevertheless, clinical study of sepsis in China still has great potential, as it is less expensive to perform clinical trials in China than in the developed countries and easy to recruit a large number of subjects.
There are some limitations in our study. First, we used the terms "sepsis" or "septic shock" in the topic field, which may have caused us to not identify some publications, such as those indexed with "Inflammation." Second, delayed publication collections from the WOS and PubMed databases can also cause bias in the study. Some papers may have already published in SCI journals, but have not been indexed by the above 2 databases. Third, the WOS and PubMed databases mainly included English-written pieces of literatures. Many non-English publications and publications in some databases or university libraries were not included.

Conclusion
Sepsis research in the world had made tremendous grown in volume during the last 3 decades, especially after the first Consensus Conference held by ACCP and SCCM in 1991. The USA leads the development of sepsis research with the most publications, highest citations, and h-index. Both the quantity and the quality of publications in sepsis research in China were remarkably improved over the past 31 years, and China became the second largest contributor by 2014. However, compared with the enormous growth in the quantity of publications, there is still a large gap between China and other leading countries in the term of research quality. Therefore, it is quite necessary to take steps to conduct high-quality sepsis studies in China.