There is no shortcut in the exploration of scientific research. The emergence of an important result cannot be separated from years of practical research and persistence of researchers.
Recently, a high-level,full-lengthresearch paper entitled Enhanced Inflammation and Suppressed Adaptive Immunity COVID-19 with Prolonged RNA Sheddinghas been published online on Cell Discovery (impact factor 38.079) by Tang Shaohua's team from Wenzhou Central Hospital, in collaboration with Westlake University. The first writer (ranking first) is Tang Shaohua, director of Central Laboratory of Wenzhou Central Hospital, and the second corresponding writer is Huang Jianping, secretary of the Party Committee and chief physician of NeurologyDepartment from Wenzhou Central Hospital. This research paper has set the highest record of the impact factor in the papers ever published by Wenzhou Central Hospital.
This paper is the research result of a joint multi-omics analysis of patients with long and short duration of COVID diseases. It studied an infected population of COVID-19 patients with long-term viral RNA positivity (LC) and short-term nucleic acid conversion to negativity (SC). From the aspect of proteomics and metabolomics, the paper analyzed the serum samples of 461 cases through systematic, longitudinal, and all-sided analysis of 1,252 proteins and 945 Changes in the levels of metabolites. The result showed that inhibition of the LXR/RXR signaling pathway in patients with long-term nucleic acid positivity in New Crown largely suppresses metabolites, activates the complement system, and inhibits migration of immune cells, thereby enhancing viral replication.
Wenzhou Central Hospital Nanbaixiang Branch (Wenzhou Sixth People's Hospital), as the designated hospital for the admission and treatment of COVID-19 pneumonia in Wenzhou, has admitted more than 150 patients (including the first case of COVID-19 pneumonia in Zhejiang, the hospital with the largest number of patients admitted in Wenzhou).In January 2020, duringthe outbreak of COVID-19 pneumonia, the hospital began to face the nucleic acid test of COVID-19 patients. Tang Shaohua's team found that there were significant differences in the duration of nucleic acid negative conversion in patients during nucleic acid test, with some patients' nucleic acid positivity lasting for a long time during the treatment process, up to 155 daysin some cases, while some patients converted to a negative status very quickly. The team analyzed this phenomenon and tried to find out the results that caused the discrepancy, but after going through all the treatment modes and analyzing the relevant statistics, no cause has been found yet.
So, Tang Shaohua's team began to consider whether there was a certain connection between long-term and short-term infected people, based on which they divided them into two groups of long-term positive viral RNA (LC) and short-term nucleic acid conversion to negative (SC) for further research. With the progress of the study, the team found that there was a lack of antibodies for the experiment, and this was the time when the situation of the COVID-19 epidemic in Wenzhou was critical. In order not to delay the study, and in the hope that the results of this study would help to provide timely and effective references for the treatment and diagnosis strategies of COVID-19 cases, the team sent someone to Nanjing, and it took great efforts before the antibodies could be brought back to Wenzhouto enable the experiment to be carried out smoothly.
Through the research data obtained from the experiment, Tang Shaohua's team was surprised to find that patients in the LC group showed higher levels of IgG antibodies and higher levels of regulatory T (Treg) cells for a longer period of time, which were summarized into a scientific article in 2020. The team submitted their hard-earned results to authoritative journals, but they were consistently rejected on the grounds that no researchers had yet conducted a study following the pattern of the two group classifications before, and it was doubtful whether scientific conclusions had been reached. At this point, due to work reasons, the team put the research aside for the time being, but everyone has always been perplexed by the further exploration on this phenomenon.
Later, Tang Shaohua, the team leader, began to think whether the phenomenon could be explained through the approaches of proteomics. Then, Tang Shaohua's team approached Westlake University, and the two sides hit it off. The research on the phenomena and samples found by Wenzhou Central Hospital team were carried out towards the research approaches of proteomics, looking for some basic protein molecular expression differences and signal pathway differences to answer the phenomenon. The result of the research was notified quickly in 2021, starting a second round of submission, however unfortunately it was rejected againfor the same reasons as before. Their attempts failed again and again, and all their efforts seemed to be going down the drain. At this point, Westlake University team suggested a different mode of research, focusing only on the changes in the phenomenon. But Tang Shaohua’s team from Wenzhou Central Hospitalheld on to their own views, because the answer they wanted was to explain the actual clinical findings, not a research done for the sake of an article.
Finally, all efforts will pay off. When everyone was at a loss, Tang Shaohua's team unexpectedlyfound that academician Li Lanjuan's team and the leading respiratory disease journal European Respiratory Journal had adopted the same grouping for their research,about which the researchers were so excited that they approached Westlake University team again, expressing their willingnessto continue following the original research approaches. Therefore, on the basis of the previous research, the team added extra contents, including picture modification, data analysis, etc., and successfully completed the manuscript the same year.
This paper, which contains countless days and nights of hard work by Tang Shaohua's team, has been published on Cell Discovery after spending more than 3 years and experiencing multiple submitting rejections, filling the gap in research on the RNA shedding mechanism of COVID-19, which is crucial to help formulate a better strategy for controlling the spread of the virus, and also providing an important theoretical basis for the current research of the widely publicized long-COVID research.
This research was greatly supported by Westlake University, as well as several organizations, including Department of Genetics and Genomic Medicine of Zhejiang Provincial People's Hospital, and Dian Diagnostics Calibra Laboratory, etc. We would like to express our sincere gratitude to all the cooperative organizations and scholars for their close cooperation.
Wenzhou Accurate Medical TestingKey Laboratory
Jointly established in 2021, Wenzhou Accurate Medical Test Key Laboratory focuses on macro-genome, human genome, tumor genome accurate testing goals, and attracts medicine-related professionalson the basis of Wenzhou Accurate Testing Center and Zhejiang Molecular Specialty Key Demonstration Laboratory. Professor Huang Jianping of Wenzhou Central Hospital was appointed as the first director of the Key Laboratory and Professor Tang Shaohua of the Central Laboratory as the director of the first Academic Committee. Wenzhou Accurate TestingKey Laboratory is well-equipped with four illumination high-throughput sequencing systems, over 30 fluorescence quantitative PCR systems, three Sanger sequencers, one QIAGEN pyrophosphoric acid sequencer, Affymetrix gene chip scanner, chemiluminiscence gel imaging system, etc., which can provide cellular, molecular, protein and other aspects of research for accurate testing, and make the testing equipment available to the public.
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