Publications by authors named "Lanjuan Li"

589 Publications

Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms.

J Infect 2021 Jul 26. Epub 2021 Jul 26.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China.

Hepatitis E virus (HEV) infection has many extrahepatic manifestations as well as liver symptoms. Multiple studies have shown that HEV infection has symptoms related to the nervous system, kidneys, cryoglobulinemia, hematological system, reproductive system, autoimmunity and pancreas. Hence, HEV infection should be considered as a systemic disease, rather than solely a liver disease. The extrahepatic manifestations induced by different genotypes of HEV vary. The severity of these diseases does not necessarily correlate with the severity of HEV infection, and even asymptomatic HEV infection may trigger and cause systemic diseases. Patients with systemic manifestations of HEV infection should have priority for antiviral therapy, which could alleviate or improve the extrahepatic manifestations related to HEV infection. However, the extrahepatic manifestations caused by different genotypes of HEV and their corresponding mechanisms have not been clearly identified. This review discusses the extrahepatic manifestations related to HEV infection and their triggering mechanisms.
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http://dx.doi.org/10.1016/j.jinf.2021.07.021DOI Listing
July 2021

Role of prebiotics in enhancing the function of next-generation probiotics in gut microbiota.

Crit Rev Food Sci Nutr 2021 Jul 29:1-18. Epub 2021 Jul 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.
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http://dx.doi.org/10.1080/10408398.2021.1958744DOI Listing
July 2021

Health-Related Quality of Life and Its Influencing Factors in Patients with Hepatitis B: A Cross-Sectional Assessment in Southeastern China.

Can J Gastroenterol Hepatol 2021 7;2021:9937591. Epub 2021 Jul 7.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Health-related quality of life (HRQoL) is an important aspect in the management of patients with hepatitis B (HB), which remains a serious health problem in China. There have been relatively few HRQoL studies involving Chinese patients with HB. The aim of this study was to analyze HRQoL in patients diagnosed with HB living in Zhejiang Province, China. A cross-sectional sample of 98 patients with chronic HB (CHB), 56 patients with advanced HB that have developed cirrhosis, and 48 healthy controls (HCs), all from Zhejiang Province, was used in this study. HRQoL was assessed using Short-Form 36 (SF-36) version 2, European quality of life questionnaire-5 dimensions (EQ-5D), and chronic liver disease questionnaire (CLDQ). Intergroup score differences were detected with tests. Factors with a significant effect on HRQoL were identified with Spearman correlational analyses. Patients with HB (both groups) had lower SF-36 scores than HCs ( < 0.01), with the exception of general health subscores. Patients with HB cirrhosis had the lowest scores in the EQ-5D visual analog scale (VAS) component. Furthermore, patients with HB cirrhosis had lower ( < 0.01) CLDQ scores than patients with CHB. In our HB patient cohort, disease stage and income level were the factors most associated with HRQoL variables; age, education level, and marital status were, each, also significantly associated with some HRQoL variables in patients with HB in our study ( < 0.05 or < 0.01). HRQoL is diminished in patients with HB in southeastern China. Disease stage and income emerged as key determinants of HRQoL scores. Augmenting social and medical supports for patients with HB, especially those with a socioeconomic status and an advanced disease stage, may help to enhance HRQoL.
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http://dx.doi.org/10.1155/2021/9937591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279869PMC
July 2021

Preliminary Assessment of Chinese Strategy in Controlling Reemergent Local Outbreak of COVID-19.

Front Public Health 2021 2;9:650672. Epub 2021 Jul 2.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Reemergent local outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China, yet few Chinese response strategies and its evaluation have been reported. This study presents a preliminary assessment of Chinese strategy in controlling reemergent local outbreaks of COVID-19. Time course of accumulative and daily new cases and time-varying reproductive numbers (Rt) of outbreak areas were presented. The asymptomatic rate, days required to control the outbreaks, seeding time (ST), and doubling time (DT) of areas with over 96 reemergent cases were calculated. National and local year-on-year growth rates of gross domestic product (GDP) were presented. Accumulative numbers of 30, 8, 11, 430, 15, 139, 1,067, 382, 42, and 94 confirmed reemergent COVID-19 cases were diagnosed in Hulun Buir, Shanghai, Tianjin, Kashgar, Qingdao, Dalian, Urumchi, Beijing, Jilin, and Harbin, respectively. Among them, maximum rate of asymptomatic infections was 81.9%. Time required to control the local outbreaks in the areas given above varied from 29 to 51 days. After activation of outbreak responses, the late-stage DTs of Kashgar, Urumchi, Beijing, and Dalian were apparently lengthened compared to the early-stage DTs. Although the year-on-year GDP growth rate of Urumchi was slightly affected, the GDP growth rate of Dalian, Beijing, Jilin, and Harbin kept rising during the reemergence. Moreover, the year-on-year GDP growth rate of Mainland China turned positive regardless of the reemergent local outbreaks. In general, the Chinese strategy to maintain the status of no or minimal transmission was effective in balancing the control of COVID-19 reemergent local outbreak and the recovery of economy.
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http://dx.doi.org/10.3389/fpubh.2021.650672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283522PMC
July 2021

Corrigendum: Identification of a Potential miRNA-mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF.

Front Mol Biosci 2021 29;8:705683. Epub 2021 Jun 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

[This corrects the article DOI: 10.3389/fmolb.2021.657631.].
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http://dx.doi.org/10.3389/fmolb.2021.705683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276013PMC
June 2021

Metabolic profile of irradiated whole blood by chemical isotope-labeling liquid chromatography-mass spectrometry.

J Pharm Biomed Anal 2021 Jul 6;204:114247. Epub 2021 Jul 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, Zhejiang Province, 310003, China.

Irradiated blood is a new type of blood product used to prevent transfusion-associated graft-versus-host disease. However, the effects of irradiation on the metabolism of plasma, red blood cells (RBCs), and peripheral blood mononuclear cells (PBMCs) are largely unknown. We developed a workflow for testing metabolic changes in whole blood to determine the impact of irradiation by chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Blood parameters, PBMC proliferation and apoptosis were examined before and after irradiation. Next, the amine/phenol metabolites in the blood components were assayed by C- andC-dansylation labeling LC-MS. We identified 1654, 1730, and 1666 peak pairs in plasma, RBCs, and PBMCs, respectively. We screened out 367, 177, and 219 significant metabolites in plasma, RBCs, and PBMCs, respectively, by principle component analyses, volcano plots, and Venn plots. Metabolic pathway analyses showed that irradiation modulated taurine and hypotaurine metabolism in plasma and purine metabolism in RBCs and PBMCs. Changes in potential biomarkers, including an increase in hypoxanthine level and a decrease in adenine level, may be related to the dysfunction of DNA synthesis in PBMCs. The decreased AMP level in RBCs may interfere with RBC storage lesions. Our research provides a more comprehensive perspective on blood metabolism associated with irradiation.
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http://dx.doi.org/10.1016/j.jpba.2021.114247DOI Listing
July 2021

Improved functionality of Ligilactobacillus salivarius Li01 in alleviating colonic inflammation by layer-by-layer microencapsulation.

NPJ Biofilms Microbiomes 2021 07 9;7(1):58. Epub 2021 Jul 9.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.
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http://dx.doi.org/10.1038/s41522-021-00228-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270932PMC
July 2021

Attention-Guided Discriminative Region Localization and Label Distribution Learning for Bone Age Assessment.

IEEE J Biomed Health Inform 2021 Jul 7;PP. Epub 2021 Jul 7.

Bone age assessment (BAA) is clinically important as it can be used to diagnose endocrine and metabolic disorders during child development. Existing deep learning based methods for classifying bone age use the global image as input, or exploit local information by annotating extra bounding boxes or key points. However, training with the global image underutilizes discriminative local information, while providing extra annotations is expensive and subjective. In this paper, we propose an attention-guided approach to automatically localize the discriminative regions for BAA without any extra annotations. Specifically, we first train a classification model to learn the attention maps of the discriminative regions, finding the hand region, the most discriminative region (the carpal bones), and the next most discriminative region (the metacarpal bones). Guided by those attention maps, we then crop the informative local regions from the original image and aggregate different regions for BAA. Instead of taking BAA as a general regression task, which is suboptimal due to the label ambiguity problem in the age label space, we propose using joint age distribution learning and expectation regression, which makes use of the ordinal relationship among hand images with different individual ages and leads to more robust age estimation. Extensive experiments are conducted on the RSNA pediatric bone age data set. {\color{red} Without using extra manual} annotations, our method achieves competitive results compared with existing state-of-the-art deep learning-based methods that require manual annotation. Code is available at \url{https://github.com/chenchao666/Bone-Age-Assessment}.
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http://dx.doi.org/10.1109/JBHI.2021.3095128DOI Listing
July 2021

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases.

Neurosci Bull 2021 Jul 3. Epub 2021 Jul 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.
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http://dx.doi.org/10.1007/s12264-021-00730-8DOI Listing
July 2021

Corrigendum to "Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus".

Can J Infect Dis Med Microbiol 2021 4;2021:9756586. Epub 2021 Jun 4.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.

[This corrects the article DOI: 10.1155/2021/6632266.].
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http://dx.doi.org/10.1155/2021/9756586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205571PMC
June 2021

Integrative proteomics reveals the role of E3 ubiquitin ligase SYVN1 in hepatocellular carcinoma metastasis.

Cancer Commun (Lond) 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, P. R. China.

Background: Tumor metastasis is a major factor for poor prognosis of hepatocellular carcinoma (HCC), but the relationship between ubiquitination and metastasis need to be studied more systematically. We analyzed the ubiquitinome of HCC in this study to have a more comprehensive insight into human HCC metastasis.

Methods: The protein ubiquitination levels in 15 HCC specimens with vascular invasion and 15 without vascular invasion were detected by ubiquitinome. Proteins with significantly different ubiquitination levels between HCCs with and without vascular invasion were used to predict E3 ubiquitin ligases associated with tumor metastasis. The topological network of protein substrates and corresponding E3 ubiquitin ligases was constructed to identify the key E3 ubiquitin ligase. Besides, the growth, migration and invasion ability of LM3 and HUH7 hepatoma cell lines with and without SYVN1 expression interference were measured by cell proliferation assay, subcutaneous tumor assay, umphal vein endothelium tube formation assay, transwell migration and invasion assays. Finally, the interacting proteins of SYVN1 were screened and verified by protein interaction omics, immunofluorescence, and immunoprecipitation. Ubiquitin levels of related protein substrates in LM3 and HUH7 cells were compared in negative control, SYVN1 knockdown, and SYVN1 overexpression groups.

Results: In this study, our whole-cell proteomic dataset and ubiquitinomic dataset contained approximately 5600 proteins and 12,000 ubiquitinated sites. We discovered increased ubiquitinated sites with shorter ubiquitin chains during the progression of HCC metastasis. In addition, proteomic and ubiquitinomic analyses revealed that high expression of E3 ubiquitin-protein ligase SYVN1 is related with tumor metastasis. Furthermore, we found that SYVN1 interacted with heat shock protein 90 (HSP90) and impacted the ubiquitination of eukaryotic elongation factor 2 kinase (EEF2K).

Conclusions: The ubiquitination profiles of HCC with and without vascular invasion were significantly different. SYVN1 was the most important E3 ubiquitin-protein ligase responsible for this phenomenon, and it was related with tumor metastasis and growth. Therefore, SYVN1 might be a potential therapeutic target for HCC.
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http://dx.doi.org/10.1002/cac2.12192DOI Listing
July 2021

The Salivary Microbiota, Cytokines, and Metabolome in Patients with Ankylosing Spondylitis Are Altered and More Proinflammatory than Those in Healthy Controls.

mSystems 2021 Jun 22;6(3):e0117320. Epub 2021 Jun 22.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China.

The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the present study, compared to that observed in healthy controls (HCs), AS saliva was depleted of Bacilli such as Streptococcus, enriched with Clostridia such as , and enriched with opportunistic pathogens from such as Brucella spp. and Campylobacter concisus. AS saliva was enriched with 16 cytokines related to inflammation, such as soluble IL-6 receptor α (sIL-6Rα), interleukin 2 (IL-2), IL-10, IL-11, IL-12p40, IL-12p70, IL-20, IL-26, IL-27, IL-28A, IL-29, alpha 2 interferon (IFN-α2), IFN-β, and matrix metalloproteinase 3 (MMP-3). AS saliva was also enriched with hazardous compounds, such as cadaverine and putrescine. AS-altered salivary bacteria, compounds, and cytokines are closely linked with disease indicators. Oral cleaning reduced the levels of proinflammatory cytokines and hazardous compounds in AS saliva compared with HC saliva. AS saliva induced the production of more proinflammatory cytokines, such as IL-12p70 and IL-8, by THP-1 monocyte-derived macrophages, than did HC saliva. The results highlight the importance of salivary microbes, cytokines, and compounds in the development and treatment of AS and provide new ideas for the pathogenesis and treatment of AS. Ankylosing spondylitis (AS) affects as much as 0.32% of the population in some districts and causes work disability in one-third of these patients. Microbes are considered to play important roles in AS pathogenesis, and the mouth links the environment to the lungs and the gut. Our results showed that opportunistic pathogens such as Brucella and Campylobacter are enriched in the saliva of AS patients with ankylosing spondylitis. In addition, proinflammatory cytokines and hazardous materials such as putrescine were also enriched in the saliva of AS patients.[AQ1 sentence edit] Interestingly, the opportunistic pathogens and hazardous materials detected in the saliva of AS patients were associated with disease indexes. The saliva of AS patients was shown to induce immune cells to secrete proinflammatory cytokines . Reducing the levels of salivary microbes can significantly reduce the hazardous materials present in the saliva of AS patients. Our results provide a new perspective on the potential role of salivary microbes, cytokines, and hazardous compounds in the pathogenesis and treatment of AS.
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http://dx.doi.org/10.1128/mSystems.01173-20DOI Listing
June 2021

Identification of Monocytes Associated with Severe COVID-19 in the PBMCs of Severely Infected patients Through Single-Cell Transcriptome Sequencing.

Engineering (Beijing) 2021 Jun 12. Epub 2021 Jun 12.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (), epiregulin (), and cytokine interleukin-18 () gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog () signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.
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http://dx.doi.org/10.1016/j.eng.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196473PMC
June 2021

Association of ACEi/ARB Use and Clinical Outcomes of COVID-19 Patients With Hypertension.

Front Cardiovasc Med 2021 31;8:577398. Epub 2021 May 31.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Evidence has shown that angiotensin-converting enzyme 2 (ACE2), which can be upregulated after angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, may play a dual role in the pathogenesis and progression of coronavirus disease 2019 (COVID-19). We aimed to assess the association between the use of ACEi/ARB and the outcome of COVID-19 patients with preexisting hypertension in non-endemic areas. From January 17, 2020, to February 19, 2020, 286 patients with hypertension were enrolled in this retrospective study out of 1,437 COVID-19 patients from 47 centers in Zhejiang and Jiangsu Province. The composite endpoints consisted of mechanical ventilation, intensive care unit (ICU) admission, or death. Cox proportional hazards analysis was performed to assess the association between ACEi/ARB and clinical outcomes of COVID-19 patients with hypertension. In the main analysis, 103 patients receiving ACEi/ARB were compared with 173 patients receiving other regimens. Overall, 44 patients (15.94%) had an endpoint event. The risk probability of crude endpoints in the ACEi/ARB group (12.62%) was lower than that in the non-ACEi/ARB group (17.92%). After adjusting for confounding factors by inverse probability weighting, the results showed that the use of ACEi/ARB reduced the occurrence of end events by 47% [hazard ratio (HR) = 0.53; 95% CI, 0.34-0.83]. Similar results were obtained in multiple sensitivity analyses. In this retrospective study, among COVID-19 patients with hypertension, the use of ACEi/ARB is not associated with an increased risk of disease severity compared with patients without ACEi/ARB. The trends of beneficial effects of ACEi/ARB need to be further evaluated in randomized clinical trials.
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http://dx.doi.org/10.3389/fcvm.2021.577398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202940PMC
May 2021

The Application of Mesenchymal Stem Cells in the Treatment of Liver Diseases: Mechanism, Efficacy, and Safety Issues.

Front Med (Lausanne) 2021 31;8:655268. Epub 2021 May 31.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Mesenchymal stem cell (MSC) transplantation is a novel treatment for liver diseases due to the roles of MSCs in regeneration, fibrosis inhibition and immune regulation. However, the mechanisms are still not completely understood. Despite the significant efficacy of MSC therapy in animal models and preliminary clinical trials, issues remain. The efficacy and safety of MSC-based therapy in the treatment of liver diseases remains a challenging issue that requires more investigation. This article reviews recent studies on the mechanisms of MSCs in liver diseases and the associated challenges and suggests potential future applications.
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http://dx.doi.org/10.3389/fmed.2021.655268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200416PMC
May 2021

Impact of Total Epinephrine Dose on Long Term Neurological Outcome for Cardiac Arrest Patients: A Cohort Study.

Front Pharmacol 2021 28;12:580234. Epub 2021 May 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Although epinephrine is universally acknowledged to increase return of spontaneous circulation (ROSC) after cardiac arrest, its balanced effects on later outcomes remain uncertain, causing potential harm during post-resuscitation phase. Recent studies have questioned the efficacy and potential deleterious effects of epinephrine on long-term survival and neurological outcomes, despite that the adverse relationship between epinephrine dose and outcome can be partially biased by longer CPR duration and underlying comorbidities. This study explored the long-term effect of epinephrine when used in a cohort of patients that underwent cardiac arrest during cardiopulmonary resuscitation. The data were originally collected from a retrospective institutional database from January 2007 to December 2015 and are now available on Dryad (via: https://doi.org/10.5061/dryad.qv6fp83). Use of epinephrine was coded by dose (<2 mg, 2 mg, 3-4 mg, ≥5 mg). A favorable neurological outcome was defined using a Cerebral Performance Category (CPC) 1 or 2. The association between epinephrine dosing and 3-months neurological outcome was analyzed by univariate analysis and multivariate logistic regression. Univariate and multivariate analysis demonstrated a negative association between total epinephrine dose and neurological outcome. Of the 373 eligible patients, 92 received less than 2 mg of epinephrine, 60 received 2 mg, 97 received 3-4 mg and 124 received more than 5 mg. Compared to patients who received less than 2 mg of epinephrine, the adjusted odds ratio (OR) of a favorable neurological outcome was 0.8 (95% confidence interval [CI]: 0.38-1.68) for 2 mg of epinephrine, 0.43 (95% confidence interval [CI]: 0.21-0.89) for 3-4 mg of epinephrine and 0.40 (95% confidence interval [CI]: 0.17-0.96) for more than 5 mg of epinephrine. In this cohort of patients who achieved ROSC, total epinephrine dosing during resuscitation was associated with a worse neurological outcome three months after cardiac arrest, after adjusting other confounding factors. Further researches are needed to investigate the long-term effect of epinephrine on cardiac arrest patients.
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http://dx.doi.org/10.3389/fphar.2021.580234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193671PMC
May 2021

Iron Regulates the Warburg Effect and Ferroptosis in Colorectal Cancer.

Front Oncol 2021 18;11:614778. Epub 2021 May 18.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Iron promotes the proliferation of cancer cells, but it also contributes to cell death. Here we explored whether iron could promote the Warburg effect of colorectal cancer (CRC) cells and suppress sensitivity to ferroptosis by inducing reactive oxygen species (ROS) and regulating nuclear factor erythroid 2-related factor 2 (NRF2). In this study, cell proliferation abilities were measured by CCK-8, EdU incorporation, and colony formation assays. Seahorse XF96 respirometry assays were used to detect the Warburg effect and the level of ROS was assess by DCFH-DA fluorescent probes. Results showed that iron exposure promoted the Warburg effect of CRC cells by inducing ROS and activating NRF2 both and . In addition, iron exposure also induced ferroptosis in CRC cells, but at the same time its inhibitory proteins SLC7A11 and GPX4 were also upregulated, indicating an enhanced resistance to ferroptosis. Our results revealed that iron can effectively promote tumorigenesis. Meanwhile, iron elimination or a low-iron diet might be valid therapeutic approaches for CRC.
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http://dx.doi.org/10.3389/fonc.2021.614778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169994PMC
May 2021

Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double-Blind, Dose Escalation, Placebo- and Positive-Controlled, Phase 1/2 Trial.

Adv Sci (Weinh) 2021 Jun 3:e2002751. Epub 2021 Jun 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Tetanus is a fatal but vaccine-preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)-based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double-blind, dose escalation, placebo- and positive-controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT-Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT-Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment-related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen-specific CD4+/CD8+ T-cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.
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http://dx.doi.org/10.1002/advs.202002751DOI Listing
June 2021

Mitochondrial pyruvate carrier 1: a novel prognostic biomarker that predicts favourable patient survival in cancer.

Cancer Cell Int 2021 May 31;21(1):288. Epub 2021 May 31.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Shangcheng District, Hangzhou, 310003, China.

Mitochondrial pyruvate carrier 1 (MPC1) is a key metabolic protein that regulates the transport of pyruvate into the mitochondrial inner membrane. MPC1 deficiency may cause metabolic reprogramming. However, whether and how MPC1 controls mitochondrial oxidative capacity in cancer are still relatively unknown. MPC1 deficiency was recently found to be strongly associated with various diseases and cancer hallmarks. We utilized online databases and uncovered that MPC1 expression is lower in many cancer tissues than in adjacent normal tissues. In addition, MPC1 expression was found to be substantially altered in five cancer types: breast-invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and prostate adenocarcinoma (PRAD). However, in KIRC, LUAD, PAAD, and PRAD, high MPC1 expression is closely associated with favourable prognosis. Low MPC1 expression in BRCA is significantly associated with shorter overall survival time. MPC1 expression shows strong positive and negative correlations with immune cell infiltration in thymoma (THYM) and thyroid carcinoma (THCA). Furthermore, we have comprehensively summarized the current literature regarding the metabolic reprogramming effects of MPC1 in various cancers. As shown in the literature, MPC1 expression is significantly decreased in cancer tissue and associated with poor prognosis. We discuss the potential metabolism-altering effects of MPC1 in cancer, including decreased pyruvate transport ability; impaired pyruvate-driven oxidative phosphorylation (OXPHOS); and increased lactate production, glucose consumption, and glycolytic capacity, and the underlying mechanisms. These activities facilitate tumour progression, migration, and invasion. MPC1 is a novel cancer biomarker and potentially powerful therapeutic target for cancer diagnosis and treatment. Further studies aimed at slowing cancer progression are in progress.
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http://dx.doi.org/10.1186/s12935-021-01996-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166087PMC
May 2021

Profiling T cell receptor β-chain in responders after immunization with recombinant hepatitis B vaccine.

J Gene Med 2021 May 28:e3367. Epub 2021 May 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: T cells with edited T cell receptor β-chain variable (TRBV) are involved in the immune response to recombinant hepatitis B surface antigen (rHBsAg) vaccine and the production of hepatitis B surface antibody (HBsAb). The immune repertoire (IR) profile and mechanism of vaccination positive responders (VPR) with rHBsAg are not fully understood.

Methods: The IR of six VPRs (HBsAb+, HbsAg-) with rHBsAg vaccination was established by the high throughput sequencing technique and bioinformatics analysis and compared with those in five vaccination negative responders (VNRs) (HbsAb-, HbsAg-) who were also inoculated with rHBsAg. The repertoire features of the BV, BJ and V (CDR3) J genes and immune diversity in peripheral blood mononuclear cells, respectively, were analyzed for each subject.

Results: There was no significant difference in sequencing amplification indices of each sample. However, TRBV15/BJ2-3 demonstrated significantly high expression levels in VPR compared to those in the VNR group (both p < 0.05). Further results showed that the BV15/BJ2-5 level was significantly increased for VPR compared to that of VNR group. Interestingly, the motif of CDR3 in TRBV15/BJ2-5 was mostly expressed as "GGETQ" or "GETQ". Additionally, there was no remarkable difference between the two groups of distribution with respect to the different clone expression levels of V (CDR3) J.

Conclusions: The features of IR in the VPR and VNR will contribute to the exploration of the mechanism of the positive response to rHBsAg, and also contribute to development of optimized hepatitis B vaccine, in addition to providing a partial interpretation of the VNR who has a relatively low infection with HBV.
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http://dx.doi.org/10.1002/jgm.3367DOI Listing
May 2021

Identification of a Potential miRNA-mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF.

Front Mol Biosci 2021 28;8:657631. Epub 2021 Apr 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA-mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis.

Methods: In patients with HBV-ACLF meeting COSSH-ACLF criteria, age, liver cirrhosis and INR were independent risk factors for 28-day and 90-day poor prognosis. COSSH-ACLFs was a superior prognostic model. mir-6840-3p-JADE2 may promote the progression of ACLF and lead to poor prognosis. Meanwhile, mir-6840-3p and mir-6861-3p can be used as markers of short-term poor prognosis. Finally, ALSS treatment is not only the blood material exchange of patients, but also changes part of the immune state of patients. Among them, cytokine cytokine receptor interaction may play an important role in determining the therapeutic effect.

Methods: Transcriptome-wide microRNA (miRNA) and mRNA microarrays were used to define the miRNA and mRNA expression profiles of the PBMCs of HBV-ACLF patients in a discovery cohort. The targets of the miRNAs were predicted. We built a miRNA-mRNA regulatory network through bioinformatics analysis, and used quantitative real-time polymerase chain reaction (qRT-PCR) to assess the importance of candidate miRNAs and mRNAs. We also assessed the direct and transcriptional regulatory effects of miRNAs on target mRNAs using a dual-luciferase reporter assay.

Results: The miRNA/mRNA PBMC expression profiles of the discovery cohort, of whom eight survived and eight died, revealed a prognostic interactive network involving 38 miRNAs and 313 mRNAs; this was constructed by identifying the target genes of the miRNAs. We validated the expression data in another cohort, of whom 43 survived and 35 died; miR-6840-3p, miR-6861-3p, JADE2, and NR3C2 were of particular interest. The levels of miR-6840-3p and miR-6861-3p were significantly increased in the PBMCs of the patients who died, and thus predicted prognosis (areas under the curve values = 0.665 and 0.700, respectively). The dual-luciferase reporter assay indicated that miR-6840-3p directly targeted JADE2.

Conclusion: We identified a prognostic miRNA-mRNA co-regulatory network in the PBMCs of HBV-ACLF patients. miR-6840-3p-JADE2 is a potential miRNA-mRNA pair contributing to a poor prognosis.
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http://dx.doi.org/10.3389/fmolb.2021.657631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113841PMC
April 2021

Mental Health Outcomes Among Civil Servants Aiding in Coronavirus Disease 2019 Control.

Front Public Health 2021 29;9:601791. Epub 2021 Apr 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, College of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

To assess the psychiatric status of Chinese civil servants aiding in coronavirus disease 2019 (COVID-19) control. During the COVID-19 pandemic, Chinese civil servants have faced high workloads that may contribute to mental disorders. We assessed the prevalence of both depression and anxiety symptoms among civil servants in Jiangsu and surrounding provinces using the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7) scale. The PHQ-9 and GAD-7 were used to assess the severity of symptoms of depression and anxiety, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. In total, 867 Chinese civil servants aiding in COVID-19 control were included in our study. Overall, 37.25 and 38.06% of all respondents reported having symptoms of depression and anxiety, respectively. Respondents who were younger and more educated and those who had fewer years of work experience had higher scores for both depression and anxiety. Multivariable logistic regression analysis showed that being a woman, being younger, having more education and having fewer years of work experience were associated with a higher risk of symptoms of depression and anxiety. However, whether they had experience combating infectious diseases or worked in frontline, there was no significant difference between respondents with and without experience, as well as between frontline and non-frontline workers, in both symptoms of depression and anxiety. The civil servants aiding in COVID-19 control reported suffering from varying degrees of mental disorders. Therefore, more attention should be devoted to the psychological distress of these civil servants.
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http://dx.doi.org/10.3389/fpubh.2021.601791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118382PMC
May 2021

Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.

Br J Clin Pharmacol 2021 May 13. Epub 2021 May 13.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.

Aims: Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19.

Methods: A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset.

Results: The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter.

Conclusions: IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study.
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http://dx.doi.org/10.1111/bcp.14898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239515PMC
May 2021

Effects of Pediococcus pentosaceus LI05 on immunity and metabolism in germ-free rats.

Food Funct 2021 Jun 7;12(11):5077-5086. Epub 2021 May 7.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Many Pediococcus spp. have health-promoting benefits, and Pediococcus pentosaceus LI05 is one such species that was proved to be beneficial in previous studies. Our research aimed to determine the immune and metabolic effects of P. pentosaceus LI05 on germ-free rats. Germ-free rats were gavaged with P. pentosaceus LI05 suspensions (1 × 10 CFU) for 2 weeks, and 3 weeks later, blood, spleen, intestine and liver samples were gathered for metabolome, intestine morphology, immunity, and transcriptomics analyses. Oral gavage of P. pentosaceus LI05 reduced the bodyweight of rats, which manifested as increased fecal carbohydrate concentrations, decreased intestinal fat intake and the hepatic fat synthesis gene expression, and accelerated fat-to-glycogen conversion. In addition, P. pentosaceus LI05 exhibited an anti-inflammatory ability, reducing serum proinflammatory cytokine levels and increasing intestinal subepidermal CD4 cell levels. Furthermore, administration of P. pentosaceus LI05 increased the antimicrobial ability and enhanced the liver detoxification function. These results indicate that as a probiotic, P. pentosaceus LI05 ameliorates the hampered immune response of GF animals and improves the metabolism of fat and toxic substances.
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http://dx.doi.org/10.1039/d0fo02530eDOI Listing
June 2021

Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial.

Phytomedicine 2021 May 16;85:153242. Epub 2020 May 16.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong province, 510120 PR China. Electronic address:

Background: Coronavirus disease 2019 (Covid-19) has resulted in a global outbreak. Few existing targeted medications are available. Lianhuaqingwen (LH) capsule, a repurposed marketed Chinese herb product, has been proven effective for influenza.

Purpose: To determine the safety and efficacy of LH capsule in patients with Covid-19.

Methods: We did a prospective multicenter open-label randomized controlled trial on LH capsule in confirmed cases with Covid-19. Patients were randomized to receive usual treatment alone or in combination with LH capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the rate of symptom (fever, fatigue, coughing) recovery.

Results: We included 284 patients (142 each in treatment and control group) in the full-analysis set. The recovery rate was significantly higher in treatment group as compared with control group (91.5% vs. 82.4%, p = 0.022). The median time to symptom recovery was markedly shorter in treatment group (median: 7 vs. 10 days, p < 0.001). Time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) was also significantly shorter in treatment group (all p < 0.001). The rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, p < 0.001) and clinical cure (78.9% vs. 66.2%, p = 0.017) was also higher in treatment group. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings (both p > 0.05). No serious adverse events were reported.

Conclusion: In light of the safety and effectiveness profiles, LH capsules could be considered to ameliorate clinical symptoms of Covid-19.
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http://dx.doi.org/10.1016/j.phymed.2020.153242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229744PMC
May 2021

High-Coverage Metabolome Analysis Reveals Significant Diet Effects of Autoclaved and Irradiated Feed on Mouse Fecal and Urine Metabolomics.

Mol Nutr Food Res 2021 06 10;65(12):e2100110. Epub 2021 May 10.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Scope: Using metabolomics to study the relations of nutrition and health requires stringent control of the experimental conditions used in an animal model. This work investigates the diet effects of autoclaved and irradiated feed on mouse urine and fecal metabolomics.

Methods And Results: C57BL/6 mice are fed normal-irradiation sterilized diet (n = 9), autoclave sterilized diet (n = 9), and high-irradiation sterilized diet (n = 9) for 4 weeks. Differential chemical isotope labeling liquid chromatography mass spectrometry is used to quantify the metabolome variations of urine and feces collected at five time points. Significant differences are observed in urine or fecal metabolomes of mice fed autoclaved diet versus mice fed high-irradiation diet or fed normal-irradiation diet, while the differences are small between the mice fed normal-irradiation and high-irradiation diet. Correlation studies of metabolite changes of diet- and aging-related biomarkers indicate a large overlap of significantly affected metabolites by the two factors.

Conclusions: Diet can be a confounding factor that needs to be carefully considered when a metabolomics study is designed and metabolomic results of a mouse model of nutritional or other biological study are interpreted. Using the same sterilized diet for a given metabolomics project is essential to control the diet effect.
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http://dx.doi.org/10.1002/mnfr.202100110DOI Listing
June 2021

Microbiome-miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities.

Rheumatol Int 2021 Sep 15;41(9):1567-1575. Epub 2021 Apr 15.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, People's Republic of China.

The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between pro- and anti-inflammatory factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome-miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has not been uncovered yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome-miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.
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http://dx.doi.org/10.1007/s00296-021-04798-3DOI Listing
September 2021

Gut mycobiota alterations in patients with COVID-19 and H1N1 infections and their associations with clinical features.

Commun Biol 2021 04 13;4(1):480. Epub 2021 Apr 13.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The relationship between gut microbes and COVID-19 or H1N1 infections is not fully understood. Here, we compared the gut mycobiota of 67 COVID-19 patients, 35 H1N1-infected patients and 48 healthy controls (HCs) using internal transcribed spacer (ITS) 3-ITS4 sequencing and analysed their associations with clinical features and the bacterial microbiota. Compared to HCs, the fungal burden was higher. Fungal mycobiota dysbiosis in both COVID-19 and H1N1-infected patients was mainly characterized by the depletion of fungi such as Aspergillus and Penicillium, but several fungi, including Candida glabrata, were enriched in H1N1-infected patients. The gut mycobiota profiles in COVID-19 patients with mild and severe symptoms were similar. Hospitalization had no apparent additional effects. In COVID-19 patients, Mucoromycota was positively correlated with Fusicatenibacter, Aspergillus niger was positively correlated with diarrhoea, and Penicillium citrinum was negatively correlated with C-reactive protein (CRP). In H1N1-infected patients, Aspergillus penicilloides was positively correlated with Lachnospiraceae members, Aspergillus was positively correlated with CRP, and Mucoromycota was negatively correlated with procalcitonin. Therefore, gut mycobiota dysbiosis occurs in both COVID-19 patients and H1N1-infected patients and does not improve until the patients are discharged and no longer require medical attention.
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http://dx.doi.org/10.1038/s42003-021-02036-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044104PMC
April 2021

Six-month follow-up of gut microbiota richness in patients with COVID-19.

Gut 2021 Apr 8. Epub 2021 Apr 8.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesm, National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, Zhejiang, China

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http://dx.doi.org/10.1136/gutjnl-2021-324090DOI Listing
April 2021

Characteristics of Viral Shedding Time in SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis.

Front Public Health 2021 19;9:652842. Epub 2021 Mar 19.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

The viral shedding time (VST) of SARS-CoV-2 mainly determines its transmission and duration of infectiousness. However, it was heterogeneous in the existing studies. Here, we performed a meta-analysis to comprehensively summarize the VST of SARS-CoV-2. We searched PubMed, Web of Science, MedRxiv, BioRxiv, CNKI, CSTJ, and Wanfang up to October 25, 2020, for studies that reported VSTs of SARS-CoV-2. Pooled estimates and 95% CIs for the VSTs were calculated using log-transformed data. The VSTs in SARS-CoV-2 infections based on different demographic and clinical characteristics, treatments and specimens were stratified by subgroup analysis. A total of 35 studies involving 3,385 participants met the inclusion criteria. The pooled mean VST was 16.8 days (95% CI: 14.8-19.4, = 99.56%) in SARS-CoV-2 infections. The VST was significantly longer in symptomatic infections (19.7 days, 95% CI: 17.2-22.7, = 99.34%) than in asymptomatic infections (10.9 days, 95% CI: 8.3-14.3, = 98.89%) ( < 0.05). The VST was 23.2 days (95% CI: 19.0-28.4, = 99.24%) in adults, which was significantly longer than that in children (9.9 days, 95% CI: 8.1-12.2, = 85.74%) ( < 0.05). The VST was significantly longer in persons with chronic diseases (24.2 days, 95% CI: 19.2-30.2, = 84.07%) than in those without chronic diseases (11.5 days, 95% CI: 5.3-25.0, = 82.11%) ( < 0.05). Persons receiving corticosteroid treatment (28.3 days, 95% CI: 25.6-31.2, = 0.00%) had a longer VST than those without corticosteroid treatment (16.2 days, 95% CI: 11.5-22.5, = 92.27%) ( = 0.06). The VST was significantly longer in stool specimens (30.3 days, 95% CI: 23.1-39.2, = 92.09%) than in respiratory tract specimens (17.5 days, 95% CI: 14.9-20.6, = 99.67%) ( < 0.05). A longer VST was found in symptomatic infections, infected adults, persons with chronic diseases, and stool specimens.
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http://dx.doi.org/10.3389/fpubh.2021.652842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017277PMC
April 2021
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