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Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential.

This study is aimed to evaluate the effectiveness of a theory-driven exercise intervention for Chinese community-dwelling (pre)frail older adults, and to clarify the underlying mechanisms of the exercise intervention in this population.A stepped-wedge cluster-randomized trial.A stepped-wedge cluster-randomized trial will be conducted among (pre)frail older adults at six communities in a county of central China. A 12-week multicomponent exercise intervention based on the integration of the Health Belief Model (HBM) and the Theory of Planned Behaviour (TPB) will be implemented to all participants during the study period. The primary outcomes are frailty, muscle mass, muscle strength and physical performance. Secondary outcomes include beliefs in exercise, exercise behaviours and other physical, mental and social functioning. Assessments will be conducted at baseline and at week 12, 24 and 36. A multilevel regression model will be used to evaluate the effectiveness of exercise interventions. A multilevel mediation model will be used to clarify the underlying mechanisms of this exercise intervention.This study is expected to provide an effective and practical mode for exercise interventions among Chinese community-dwelling (pre)frail older adults, and contribute to the existing evidence in this field.Chinese Clinical Trial Registry ChiCTR2100041981.

To investigate whether and how social support influenced frailty progression through depressive symptoms and physical activity.Of 1235 community-dwelling older adults enrolled at baseline, 778 (63.0%) undergoing at least one yearly follow-up were included in the final analysis. Data were collected on frailty, social support, depressive symptoms, physical activity and covariates.Two frailty trajectory classes were identified and labeled as alleviated frailty and deteriorated frailty. Subjective support prevented the deterioration of frailty through decreased depressive symptoms, while objective support and support utilization prevented the deterioration of frailty through increased physical activity.The pathways through which social support ameliorates frailty vary by support types. Subjective support interventions should be included in the multifactorial interdisciplinary management of frailty to address social and psychological vulnerabilities, along with objective support and support utilization interventions addressing physical inactivity.

To identify patterns of intrinsic capacity (IC) and determine the association between these patterns with incident one-year outcomes.A total of 756 older adults aged ≥ 60 years were followed up after 1 year. IC was assessed using the revised integrated care for older people screening tool, and its patterns were examined by the latent class analysis. Logistic regression models were conducted to compare the risk of adverse outcomes.Three IC patterns were identified. Both "sharp declines in sensory domain" (Class 2) and "sharp declines in locomotion, psychological, cognition and vitality domains" (Class 3) were at greater risk of disabilities and poor physical quality of life than "relatively healthy" (Class 1). The Class 3 was twice as likely to be hospitalized as Class 1.Assessment of IC could provide valuable information on stratifying older adults into heterogeneous groups, promoting targeted interventions to delay the adverse outcomes.

Frailty is common among older medical inpatients and has been found to be an independent risk factor for depression. However, few studies have explored the underlying mechanisms of the frailty-depression relationship. The present study was aimed to examine emotional regulation strategies as mediators in the frailty-depression relationship based on the process model of emotional regulation.Older medical inpatients (N=684) completed questionnaires and tests on frailty, emotional regulation strategies, and depressive symptoms.Structural equation models showed that expressive suppression and rumination, but not cognitive reappraisal, mediated the relationship between frailty and depressive symptoms (RMSEA = 0.059, CFI = 0.963, TLI = 0.957).Frail older medical inpatients habitually use expressive suppression and rumination in their daily lives, which may lead to more psychological disturbance. Interventions targeting expressive suppression and rumination might be effective in reducing the detrimental effect of frailty on psychological well-being among older medical inpatients.

BackgroundAcute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.MethodsGene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.ResultsA total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.ConclusionsOur study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.

Background: Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification. Methods: A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis. Results: The leukocyte telomere length was negatively associated with age (rho = −0.306, P＜0.01); it was shorter in middle-aged patients than in young patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P

Purpose To examine the “age-related positivity effect” and its sex differences in the pain-depression relationship among Chinese community-dwelling older adults. Design Cross-sectional design. Methods The study was conducted with a sample of 1,913 older adults in Jinan, China. Data were collected on pain intensity, age, sex, depressive symptoms, and potential covariates. Results The hierarchical linear regression analyses revealed that pain intensity was significantly related to depressive symptoms, there was a significant two-way interaction between age and pain intensity, and there was a significant three-way interaction between sex, age, and pain intensity. The Johnson-Neyman plot revealed that the relationship between pain and depressive symptoms decreased with advancing age, indicating an “age-related positivity effect.” And the age-related positivity effect in the pain-depression relationship was significant only in men, but not in women. Conclusions The study suggests that all older women and “young-old” men (younger senior citizens aged 60-79) in China are more likely to experience depressive symptoms from pain. Interventions on cognitive psychology should particularly target all older women and young-old men to reduce the detrimental effect of pain on emotional well-being.

Objective To develop and evaluate the psychometric properties of an instrument assessing beliefs in physical activity based on the integration of the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) among (pre)frail older adults. Methods A literature review and semi-structured interviews were conducted to generate the initial item pool of the instrument. A rural sample of 611 (pre)frail older adults was enrolled to examine the validity and reliability of the instrument. Results The exploratory factor analysis extracted eight factors for this instrument, explaining 71.3% of the variance in beliefs in physical activity. The confirmatory factor analysis confirmed the eight-factor structure. Linear regression models found that the integrated HBM-TPB constructs explained 65.9% of the variance in physical activity intention and 13.6% in physical activity. The Cronbach’s alpha coefficients for the factors ranged from 0.80 to 0.98, and ICCs ranged from 0.71 to 0.85. Conclusion This instrument has satisfactory construct validity, predictive validity, internal consistency reliability and test-retest reliability, and it can be used in (pre)frail older adults to measure beliefs in physical activity. Practice implications This instrument may help health care providers understand beliefs in physical activity and facilitate targeted interventions among (pre)frail older adults.

The current study validated and compared three short Geriatric Depression Scales (GDS), including the GDS-5, D'Ath GDS-4, and van Marwijk GDS-4, among 917 Chinese community-dwelling older adults. The GDS-5, D'Ath GDS-4, and van Marwijk GDS-4 presented satisfactory accuracy against the GDS-15 (area under the curve [AUC] = 0.872 to 0.952), and the GDS-5 and D'Ath GDS-4 had better accuracy than the van Marwijk GDS-4. Satisfactory accuracy (AUC = 0.842 to 0.979) for the three scales was also observed across subgroups by age, sex, education, cognitive function, and multimorbidity. The GDS-5 but not D'Ath GDS-4 and van Marwijk GDS-4 retained a 2-point optimal cutoff for depressive symptoms across subgroups. The GDS-5 (average inter-item correlation coefficient [AIIC] = 0.233) and the D'Ath GDS-4 (AIIC = 0.171) but not van Marwijk GDS-4 (AIIC = 0.128) had acceptable internal consistency. Three scales had stable test–retest reliability within a 1- to 2-week interval (intraclass correlation coefficient = 0.670 to 0.885). The GDS-5 is an accurate and reliable depression screening tool with an invariable optimal cutoff among Chinese community-dwelling older adults. The variable optimal cutoffs for the D'Ath GDS-4 and van Marwijk GDS-4 across subgroups may limit their applicability in this population. [ Research in Gerontological Nursing, 15 (6), 283–291.]

BackgroundAcute allograft rejection (AR) following renal transplantation contributes to chronic rejection and allograft dysfunction. The current diagnosis of AR remains dependent on renal allograft biopsy which cannot immediately detect renal allograft injury in the presence of AR. In this study, sensitive biomarkers for AR diagnosis were investigated and developed to protect renal function.MethodsWe analyzed pre- and postoperative data from five databases combined with our own data to identify the key differently expressed genes (DEGs). Furthermore, we performed a bioinformatics analysis to determine the immune characteristics of DEGs. The expression of key DEGs was further confirmed using the real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemical (IHC) staining in patients with AR. ROC curves analysis was used to estimate the performance of key DEGs in the early diagnosis of AR.ResultsWe identified glutamic-oxaloacetic transaminase 2 (GOT2) and syntaxin binding protein 3 (STXBP3) as key DEGs. The higher expression of STXBP3 and GOT2 in patients with AR was confirmed using RT-qPCR, ELISA, and IHC staining. ROC curve analysis also showed favorable values of STXBP3 and GOT2 for the diagnosis of early stage AR.ConclusionsSTXBP3 and GOT2 could reflect the immunological status of patients with AR and have strong potential for the diagnosis of early-stage AR.

In response to jasmonates (JAs), the JA receptor Coronatine Insensitive 1 (COI1) recruits JA-zinc-finger inflorescence meristem (ZIM)-domain (JAZ) family repressors for destruction to regulate plant growth, development, and defense. As Arabidopsis encodes 13 JAZ repressors, their functional specificity, diversity, and redundancy in JA/COI1-mediated responses remain unclear. We generated a broad range of jaz mutants based on their phylogenetic relationship to investigate their roles in JA responses. The group I JAZ6 may play an inhibitory role in resistance to Botrytis cinerea, group II (JAZ10)/III (JAZ11/12) in JA-regulated root growth inhibition and susceptibility to Pseudomonas syringae pv tomato DC3000, and group IV JAZ3/4/9 in flowering time delay and defense against insects. JAZs exhibit high redundancy in apical hook curvature. The undecuple jaz1/2/3/4/5/6/7/9/10/11/12 (jaz1-7,9-12) mutations enhance JA responses and suppress the phenotypes of coi1-1 in flowering time, rosette growth, and defense. The JA hypersensitivity of jaz1-7,9-12 in root growth, hook curvature, and leaf yellowing is blocked by coi1-1. jaz1-7,9-12 does not influence the stamen phenotypes of wild-type and coi1-1. jaz1-7,9-12 affects JA-regulated transcriptional profile and recovers a fraction of that in coi1-1. This study contributes to elucidating the specificity, diversity, and redundancy of JAZ members in JA/COI1-regulated growth, development, and defense responses.

We aimed to explore the relationship between sleep quality and frailty, and depression as a mediator and its interaction with sleep quality on frailty. This was a cross-sectional study among 936 Chinese community-dwelling adults aged≥60 years. Sleep quality, frailty and depression were measured by the Pittsburgh Sleep Quality Index (PSQI), the Frailty Phenotype and the 5-item Geriatric Depression Scale (GDS-5), respectively. We found that depression mediated the association between poor sleep quality and physical frailty, attenuating the association between poor sleep and physical frailty by 51.9%. Older adults with both poor sleep quality and depression had higher risk of frailty than those with poor sleep quality or depression alone. These results implicate multidisciplinary care for frail older adults with poor sleep quality.

A kidney transplant is often the best treatment for end-stage renal disease. Although immunosuppressive therapy sharply reduces the occurrence of acute allograft rejection (AR), it remains the main cause of allograft dysfunction. We aimed to identify effective biomarkers for AR instead of invasive kidney transplant biopsy. We integrated the results of several proteomics studies related to AR and utilized public data sources. Gene ontology (GO) and pathway analyses were used to identify important biological processes and pathways. The performance of the identified proteins was validated using several public gene expression omnibus (GEO) datasets. Samples that performed well were selected for further validation through RNA sequencing of peripheral blood mononuclear cells of patients with AR (n = 16) and non-rejection (n = 19) from our medical center. A total of 25 differentially expressed proteins (DEPs) overlapped in proteomic studies of urine and blood samples. GO analysis showed that the DEPs were mainly involved in the immune system and blood coagulation. Pathway analysis showed that the complement and coagulation cascade pathways were well enriched. We found that immunoglobulin heavy constant alpha 1 (IGHA1) and immunoglobulin κ constant (IGKC) showed good performance in distinguishing AR from non-rejection groups validated with several GEO datasets. Through RNA sequencing, the combination of IGHA1, IGKC, glomerular filtration rate, and donor age showed good performance in the diagnosis of AR with ROC AUC 91.4% (95% CI: 82–100%). Our findings may contribute to the discovery of potential biomarkers for AR monitoring.

BackgroundDiabetic kidney disease (DKD) is the primary cause of end-stage renal disease, raising a considerable burden worldwide. Recognizing novel biomarkers by metabolomics can shed light on new biochemical insight to benefit DKD diagnostics and therapeutics. We hypothesized that serum metabolites can serve as biomarkers in the progression of DKD.MethodsA cross-sectional study of 1,043 plasma metabolites by untargeted LC/MS among 89 participants identified associations between proteinuria severity and metabolites difference. Pathway analysis from differently expressed metabolites was used to determine perturbed metabolism pathways. The results were replicated in an independent, cross-sectional cohort of 83 individuals. Correlation and prediction values were used to examine the association between plasma metabolites level and proteinuria amount.ResultsDiabetes, and diabetic kidney disease with different ranges of proteinuria have shown different metabolites patterns. Cysteine and methionine metabolism pathway, and Taurine and hypotaurine metabolism pathway were distinguishable in the existence of DKD in DC (diabetes controls without kidney disease), and DKD with different ranges of proteinuria. Two interesting tetrapeptides (Asn-Met-Cys-Ser and Asn-Cys-Pro-Pro) circulating levels were elevated with the DKD proteinuria progression.ConclusionsThese findings underscore that serum metabolomics provide us biochemical perspectives to identify some clinically relevant physiopathologic biomarkers of DKD progression.

BackgroundAcute rejection (AR) in kidney transplantation is an established risk factor that reduces the survival rate of allografts. Despite standard immunosuppression, molecules with regulatory control in the immune pathway of AR can be used as important targets for therapeutic operations to prevent rejection.MethodsWe downloaded the microarray data of 15 AR patients and 37 non-acute rejection (NAR) patients from Gene Expression Omnibus (GEO). Gene network was constructed, and genes were classified into different modules using weighted gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape were applied for the hub genes in the most related module to AR. Different cell types were explored by xCell online database and single-cell RNA sequencing. We also validated the SLAMF8 and TLR4 levels in Raw264.7 and human kidney tissues of TCMR.ResultsA total of 1,561 differentially expressed genes were filtered. WGCNA was constructed, and genes were classified into 12 modules. Among them, the green module was most closely associated with AR. These genes were significantly enriched in 20 pathway terms, such as cytokine–cytokine receptor interaction, chemokine signaling pathway, and other important regulatory processes. Intersection with GS > 0.4, MM > 0.9, the top 10 MCC values and DEGs in the green module, and six hub genes (DOCK2, NCKAP1L, IL2RG, SLAMF8, CD180, and PTPRE) were identified. Their expression levels were all confirmed to be significantly elevated in AR patients in GEO, Nephroseq, and quantitative real-time PCR (qRT-PCR). Single-cell RNA sequencing showed that AR patient had a higher percentage of native T, CD1C+_B DC, NKT, NK, and monocytes in peripheral blood mononuclear cells (PBMCs). Xcell enrichment scores of 20 cell types were significantly different (pConclusionThis study demonstrates six hub genes and functionally enriched pathways related to AR. SLAMF8 is involved in the M1 macrophages via TLR4, which contributed to AR process.

Podocyte injury plays a vital role in proteinuria and nephrotic syndrome. Calcineurin (CaN) inhibitors are effective in reducing proteinuria. However, their molecular mechanism is still not fully understood. Angiopoietin-like-4 (ANGPTL4) is a secreted protein that mediates proteinuria in podocyte-related nephropathy. In this study, we established a puromycin aminonucleoside (PAN)-induced minimal-change disease (MCD) rat model and a cultured podocyte injury model. We found that CaN inhibitors protected against PAN-induced podocyte injury, accompanied by an inhibition of Nfatc1 and Angptl4 both in vivo and in vitro. Nfatc1 overexpression and knockdown experiments indicated that Angptl4 was regulated by Nfatc1 in podocytes. ChIP assays further demonstrated that Nfatc1 increased Angptl4 expression by binding to the Angptl4 promoter. In addition, overexpression and knockdown of Angptl4 revealed that Angptl4 directly induced rearrangement of the cytoskeleton of podocytes, reduced the expression of synaptopodin, and enhanced PAN-induced podocyte apoptosis. Furthermore, in a cohort of 83 MCD and 94 membranous nephropathy (MN) patients, we found increased expression of serum ANGPTL4 compared to 120 healthy controls, and there were close correlations between serum ANGPTL4 and Alb, urinary protein, urinary Alb, eGFR, Scr, and BUN in MCD patients. No obvious correlation was found in MN patients. Immunofluorescence studies indicated that increased ANGPTL4 in MCD and MN patients was located mostly in podocytes. In conclusion, our results demonstrate that CaN inhibitors ameliorate PAN-induced podocyte injury by targeting Angptl4 through the NFAT pathway, and Angptl4 plays a vital role in podocyte injury and is involved in human podocyte-related nephropathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

This study aims to examine age differences in the relationship between frailty and depression among older adults METHODS: A total of 1789 community-dwelling older adults were recruited from eastern China. Physical frailty and depressive symptoms were assessed using the Frailty Phenotype and the 5-item Geriatric Depression Scale, respectively.The hierarchical multiple linear regression analysis revealed that frailty was significantly related to depressive symptoms (β = 0.272, P0.001) and there was a significant interaction between age and frailty (β = -0.703, P0.001). The Johnson-Neyman plot revealed that the relationship between frailty and depressive symptoms became weaker as people aged.Frailty is more likely to cause depressive symptoms among the young-old than among the old-old, reflecting the age-related positivity effect. This highlights that interventions on emotional regulation should particularly target the young-old to reduce the effect of frailty on depression.

To examine the serial mediating effect of executive function and attentional bias in the relationship between frailty and depressive symptoms.Although the role of frailty in predicting depression has been well documented, the underlying mechanisms remain unclear.A cross-sectional study was conducted with 667 older inpatients aged 60-90 years in the internal medicine wards of a hospital in China.Attentional bias, frailty and depressive symptoms were assessed using the Attention to Positive and Negative Information Scale, the Physical Frailty Phenotype and the 5-item Geriatric Depression Scale. Executive function was measured using 3 tests, including digital backward, category Verbal Fluency Test and Trail Making Test. The study followed the STROBE guideline.The latent profile analysis (LPA) identified four patterns of attentional bias, namely "no positive biasno negative bias" (class 1, 9.3%), "minor positive biasno negative bias" (class 2, 48.0%), "major positive biasminor negative bias" (class 3, 25.6%) and "major positive biasno negative bias" (class 4, 17.1%). Regression analysis found that frailty was associated with depressive symptoms. Frailty was also negatively associated with executive function, which was a protective factor for attentional bias class 1, 2 and 3 with reference to class 4. Attentional bias class 1 and 2 but not class 3 was associated with depressive symptoms with reference to class 4. The joint significance test confirmed executive function and attentional bias as serial mediators linking frailty to depressive symptoms.Unlike robust older adults who have the age-related positivity effect, frail older adults have attentional bias deficits due to executive dysfunction, and consequently experience clinically relevant depressive symptoms.Healthcare providers should take executive function training and attentional bias regulation into consideration to reduce the detrimental effects of frailty on emotional well-being.

Introduction:Acute kidney injury (AKI) after cardiac surgery is independently associated with a prolonged hospital stay, increased cost of care, and increased post-operative mortality. Delayed elevation of serum creatinine (SCr) levels requires novel biomarkers to provide a prediction of AKI after cardiac surgery. Our objective was to find a novel blood biomarkers combination to construct a model for predicting AKI after cardiac surgery and risk stratification.Methods:This was a case-control study. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to Gene Expression Omnibus (GEO) dataset GSE30718 to seek potential biomarkers associated with AKI. We measured biomarker levels in venous blood samples of 67 patients with AKI after cardiac surgery and 59 control patients in two cohorts. Clinical data were collected. We developed a multi-biomarker model for predicting cardiac-surgery-associated AKI and compared it with a traditional clinical-factor-based model.Results:From bioinformatics analysis and previous articles, we found 6 potential plasma biomarkers for the prediction of AKI. Among them, 3 biomarkers, such as growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 (ST2, IL1RL1), and soluble urokinase plasminogen activator receptor (uPAR) were found to have prediction ability for AKI (area under the curve [AUC] > 0.6) in patients undergoing cardiac surgery. They were then incorporated into a multi-biomarker model for predicting AKI (C-statistic: 0.84, Brier 0.15) which outperformed the traditional clinical-factor-based model (C-statistic: 0.73, Brier 0.16).Conclusion:Our research validated a promising plasma multi-biomarker model for predicting AKI after cardiac surgery.

Acute rejection (AR) is closely associated with renal allograft dysfunction. Here, we utilised RNA sequencing (RNA-Seq) and bioinformatic methods to characterise the peripheral blood mononuclear cells (PBMCs) of patients with acute renal allograft rejection. Pretransplant blood samples were collected from 32 kidney allograft donors and 42 corresponding recipients with biopsies classified as T cell-mediated rejection (TCMR, n = 18), antibody-mediated rejection (ABMR, n = 5), and normal/non-specific changes (non-AR, n = 19). The patients with TCMR and ABMR were assigned to the AR group, and the patients with normal/non-specific changes (n = 19) were assigned to the non-AR group. We analysed RNA-Seq data for identifying differentially expressed genes (DEGs), and then gene ontology (GO) analysis, Reactome, and ingenuity pathway analysis (IPA), protein—protein interaction (PPI) network, and cell-type enrichment analysis were utilised for bioinformatics analysis. We identified DEGs in the PBMCs of the non-AR group when compared with the AR, ABMR, and TCMR groups. Pathway and GO analysis showed significant inflammatory responses, complement activation, interleukin-10 (IL-10) signalling pathways, classical antibody-mediated complement activation pathways, etc., which were significantly enriched in the DEGs. PPI analysis showed that IL-10, VEGFA, CXCL8, MMP9, and several histone-related genes were the hub genes with the highest degree scores. Moreover, IPA analysis showed that several proinflammatory pathways were upregulated, whereas antiinflammatory pathways were downregulated. The combination of NFSF14+TANK+ANKRD 33 B +HSPA1B was able to discriminate between AR and non-AR with an AUC of 92.3% (95% CI 82.8–100). Characterisation of PBMCs by RNA-Seq and bioinformatics analysis demonstrated gene signatures and biological pathways associated with AR. Our study may provide the foundation for the discovery of biomarkers and an in-depth understanding of acute renal allograft rejection.

Cognitive frailty, a potentially reversible condition describing the concurrence of physical frailty and mild cognitive impairment (MCI), has been recently proposed to incorporate subjective cognitive decline (SCD), a reversible pre-MCI state with more readily available cognitive reserve, as well as pre-physical frailty. Reversible cognitive frailty has been associated with dementia and mortality. We aimed to examine the association of reversible cognitive frailty with other adverse outcomes including disability, poor quality of life (QOL), depression, and hospitalization.This was a cohort study with 1-year follow-up among 735 Chinese community-dwelling older adults with intact cognition. Reversible cognitive frailty was operationalized with the presence of pre-physical or physical frailty identified by the Frailty Phenotype and SCD identified by the simplified SCD questionnaire including four self-report cognitive domains of memory, naming, orientation, and mathematical reasoning. Adverse outcomes included incident Activities of Daily Living (ADL)-Instrumental ADL (IADL) disability, poor physical, mental and overall QOL, depression, and hospitalization over 1-year follow-up.The prevalence of reversible cognitive frailty was 27.8%. Participants with reversible cognitive frailty had higher risk of the incidence of ADL-IADL disability, poor physical QOL, poor mental QOL, poor overall QOL, and depression (Odds Ratios: 1.67-4.38,Reversible cognitive frailty was not uncommon and associated with incident disability, poor QOL, and depression among community-dwelling older adults. Early identification of reversible cognitive frailty can facilitate targeted interventions and may promote independence in older adults.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2021.2011835.

To explore the association between self-efficacy and self-management by modelling three types of social support as mediators among stroke high-risk populations.Self-efficacy and social support (i.e. objective support, subjective support and support utilisation) are important for self-management among stroke high-risk populations. Self-efficacy activates three types of social support, and the effect of social support on self-management varies by types among chronic patients. Therefore, social support may act as a mediator between self-efficacy and self-management, and the mediating role may vary by types of social support. Disentangling the role of these different types of social support can guide tailored interventions.A cross-sectional study.This study was conducted among 448 Chinese adults at high risk for stroke. Self-efficacy, self-management and social support were assessed using the Self-Efficacy Scale, the Stroke Self-management Scale and the Social Support Rating Scale respectively. The PROCESS SPSS Macro version 3.3, model 4 was used to explore the mediating role of different types of social support in the relationship between self-efficacy and self-management. This study followed STROBE checklist for cross-sectional studies (Appendix S1).Self-efficacy improved three types of social support, and subjective support and support utilisation promoted self-management, but objective support hindered self-management. The specific indirect effect of objective support and subjective support was significant but not that of support utilisation. Objective support, subjective support and support utilisation attenuated the total effect of self-efficacy on self-management by -23.8%, 23.8% and 7.7% respectively.Mediating effect of social support in the relationship between self-efficacy and self-management varies by type, and the positive effect of subjective support is offset by the detrimental effect of objective support.Among stroke high-risk populations, interventions should target objective support and subjective support as well as self-efficacy to efficiently improve their self-management.

Sepsis, a complex multisystem disorder, is among the top causes of hospitalization and mortality in older adults. However, the mechanisms underlying the disproportionate susceptibility to sepsis and worse outcomes in the elderly are not well understood. Recently, changes in DNA methylation have been shown to be linked to aging processes and age-related diseases. Thus, we postulated that age-related changes in DNA methylation may play a role in the onset and prognosis of sepsis in elderly patients. Here, we performed genome-wide methylation profiling of peripheral blood from patients with sepsis and controls. Among the CpG sites whose methylation changes may contribute to an increase in sepsis susceptibility or mortality, 241 sites that possessed age-related changes in DNA methylation in controls may partly explain the increased risk of sepsis in older adults, and 161 sites whose methylation significantly correlated with age in sepsis group may be the potential mechanisms underlying the worse outcomes of elderly septic patients. Finally, an independent cohort was used to validate our findings. Together, our study demonstrates that age-related changes in DNA methylation may explain in part the disproportionate susceptibility and worse outcomes of sepsis in older adults.

Background: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China. Tubular injury contributes to the progression of DKD. Our study was conducted to explore the differential gene expression profiles between kidneys from patients with DKD and kidney living donors (LDs).Methods: In total, seven DKD and eighteen LD gene expression profiles from the GSE104954 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in R with the limma package. DEGs were uploaded to the g:Profiler online database to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Ingenuity pathway analysis (IPA) was carried out using online IPA software. Weighted gene co-expression network analysis (WGCNA) was performed using the WGCNA R package. By integrating DEGs and genes from the top 1 phenotype-gene associated module, we determined the hub gene. We next tested the hub gene, VCAN, in the GSE30122 dataset. We also validated the versican levels in human kidney tissues, explored immune cell type enrichment using an online database xCell, and investigated the correlation between cell types and VCAN expression.Results: A total of 563 DEGs was identified. A large number of pathways were involved in the immune response process according to the results of GO, KEGG, and IPA. Using WGCNA, we selected the lightcyan module in which genes showed the strongest correlation with the phenotype and smallest P-value. We also identified VCAN as a hub gene by integrating DEG analysis and WGCNA. Versican expression was upregulated in human diabetic kidney tissue. Moreover, versican was speculated to play a role in immune injury according to the enrichment of functions and signaling pathways. VCAN transcript levels correlate with the assembly of immune cells in the kidney.Conclusion: Immune processes played an essential role in DKD tubulointerstitium injury. The hub gene VCAN contributed to this process.

Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE) and is a major cause of SLE related deaths. Early diagnosis is essential to improve the prognosis of patients with LN. To screen the potential biomarkers associated with LN, we downloaded the gene expression profile of GSE99967 from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was utilized to construct a gene co-expression network and identify gene modules associated with LN. Gene Ontology (GO) analysis was also applied to explore the biological function of genes and identify the key module. Differentially expressed genes (DEGs) were identified and Maximal Clique Centrality (MCC) values were calculated to screen hub genes. Furthermore, we selected promising biomarkers for real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) validation in independent cohorts. Our results indicated that five hub genes, including IFI44, IFIT3, HERC5, RSAD2, and DDX60 play vital roles in the pathogenesis of LN. Importantly, IFI44 may considered as a key biomarker in LN for its diagnostic capabilities, which is also a promising therapeutic target in the future.

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Sepsis is a heterogeneous syndrome induced by infection and results in high mortality. Even though more than 100 biomarkers for sepsis prognosis were evaluated, prediction of patient outcomes in sepsis continues to be driven by clinical signs because of unsatisfactory specificity and sensitivity of these biomarkers. This study aimed to elucidate the key candidate genes involved in sepsis response and explore their downstream effects based on weighted gene co-expression network analysis (WGCNA). The dataset GSE63042 with sepsis outcome information was obtained from the Gene Expression Omnibus (GEO) database and then consensus WGCNA was conducted. We identified the hub gene SDF4 (stromal cell derived factor 4) from the M6 module, which was significantly associated with mortality. Subsequently, two datasets (GSE54514 and E-MTAB-4421) and cohort validation (n=89) were performed. Logistic regression analysis was used to build a prediction model and the combined score resulting in a satisfactory prognosis value (area under the ROC curve=0.908). The model was subsequently tested by another sepsis cohort (n=70, ROC= 0.925). We next demonstrated that endoplasmic reticulum (ER) stress tended to be more severe in patients PBMCs with negative outcomes compared to those with positive outcomes and SDF4 was related to this phenomenon. In addition, our results indicated that adenovirus-mediated Sdf4 overexpression attenuated ER stress in cecal ligation and puncture (CLP) mice lung. In summary, our study indicates that incorporation of SDF4 can improve clinical parameters predictive value for the prognosis of sepsis, and decreased expression levels of SDF4 contributes to excessive ER stress, which is associated with worsened outcomes, whereas overexpression of SDF4 attenuated such activation.

MYH9-related disease or disorder (MYH9-RD) is an autosomal dominant disease caused by mutations in the MYH9 gene. Mutations in this gene initially affect the hemic system, and other manifestations may evolve with age. Here, we report the case of a 46-year-old Chinese woman with MYH9-RD who was primarily misdiagnosed with idiopathic thrombocytopenia purpura. Exome sequencing of the patient, and the mother and son of the patient revealed a deletion mutation c.5797delC (p. R1933Efs*15) in exon 41 (encoding non-helical tailpiece, NHT) of the MYH9 gene, which consequently led to a frameshift mutation. To the best of our knowledge, this mutation has been reported in Italy once, while the substitution mutation c.5797 C>T is the most frequent mutation. Mutations that affect the NHT region cause thrombocytopenia throughout life; however, our patient presented with a more severe phenotype than previously reported, including thrombocytopenia, inclusion bodies in neutrophils, sensorineural hearing loss, nephropathy, and abnormal liver enzymes. Our goal in the current case is to prevent further progression of renal involvement and to identify other affected members in this family to provide early intervention. This case may raise awareness of MYH9-RD when diagnosing thrombocytopenia and improve our understanding of this condition.

To examine the diagnostic test accuracy (DTA) of the FRAIL-NH and four frailty screening instruments among institutionalized older adults.Cross-sectional study.Institutionalized setting, Jinan, China.A total of 305 older adults (mean age 79.3 ± 8.4 years, 57.0% female) were enrolled from nursing homes.Frailty was assessed by the FRAIL-NH, Physical Frailty Phenotype (PFP), FRAIL, Tilburg Frailty Indicator (TFI), and Groningen Frailty Indicator (GFI), respectively. The Comprehensive Geriatric Assessment (CGA) was used as a reference standard of frailty. The receiver operating characteristic (ROC) curve was plotted to examine the DTA of five frailty screening instruments against the CGA. The optimal cut-point was determined by the maximum value of the Youden index (YI, calculated as sensitivity + specificity - 1).The prevalence of frailty ranged from 25.9% (FRAIL) to 56.4% (GFI). Areas under the curve (AUCs) against the CGA ranged from 0.80 [95% confidence interval (CI) 0.74 - 0.85: FRAIL] to 0.83 (95% CI 0.78 - 0.88: PFP). At their original cut-points, all five frailty screening instruments presented low sensitivity (32.9% - 69.3%) and high specificity (80.0% - 93.8%), as well as high positive predictive values (90.7% - 94.9%) and low negative predictive values (33.2% - 48.1%). At their optimal cut-points, the sensitivity and specificity of the FRAIL-NH, PFP, and FRAIL tended to be balanced, and their correctly classified rates (76.1% - 81.3%) and kappa values (0.465 - 0.523) increased a lot. ROC contrasts showed that all five frailty screening instruments had similarly good diagnostic accuracy (χ2: 0.0003 - 1.38, P.05).In the institutionalized setting, the specific FRAIL-NH, self-report FRAIL, TFI, and GFI as well as hybrid PFP, show similarly good diagnostic properties in identifying frailty against the CGA.

Background Chronic pain (CP) is prevalent among older adults in many Western countries and its prevalence, factors, and self-reported or objective measured health impacts have been well documented. However, there is limited information on these aspects among Chinese community-dwelling older adults. Aims Our aim was to assess the prevalence of CP and identify its associated factors as well as health impacts among older adults in China. Design Cross-sectional design. Settings Community settings. Participants/Subjects A total of 1219 community-dwelling adults aged 60 years or older. Methods Data on CP, sociodemographic characteristics, comorbidity, cognitive function, and physical activity, as well as self-reported outcomes (functional disability, depression, quality of sleep, and undernutrition) and objective measured physical function, were obtained. Results Among 1,219 participants, 41.1% reported CP, of whom 16.6% experienced moderate to severe pain. The risk of CP was higher among older women with comorbidity and with depression and lower among older adults with higher educational level as well as with adequate physical activity. CP had significant associations with inadequate physical activity, functional disability, depression, poorer quality of sleep, and undernutrition, as well as worsening physical performance, poorer standing balance, and chair stands. Conclusions CP is a common problem among Chinese community-dwelling older adults, particularly among the most vulnerable subgroups, and has substantial impacts on self-reported functional disability, depression, poor quality of sleep, and undernutrition, as well as objective measured physical function. Therefore it is relevant for older adults to develop effective CP management programs.

BACKGROUND Hyperphosphatemia, hypocalcemia, and elevation of parathyroid hormone (PTH) are typical abnormalities of uremic patients with Secondary hyperparathyroidism (SHPT). However, metabolic imbalance associated with SHPT is not well understood. METHODS A total of 15 SHPT patients with an intact parathyroid hormone (iPTH) level > 600 pg/mL were set as preoperative (PR) group, 15 age- and gender-matched controls who had undergone parathyroidectomy plus forearm transplantation because of hyperparathyroidism and achieved an iPTH level

The common Chinese cuttlefish (Sepiella inermis) is an important cephalopod with nutritional and commercial value. Intensive inking stimulated by swilling seawater in transfer containers threatens the survival of cephalopods during transportation. However, the molecular basis for the inking behavior of S. inermis remains unclear. In the present study, transcriptome analysis was performed on ink sac and brain tissues from S. inermis under two different conditions, i.e. the control group (with individuals immersed in static seawater) and the experimental group (with individuals immersed in swilling seawater) to determine the global gene expression differences. The individuals from the experimental group ejected ink in response to the swilling of seawater. 330,699 unigenes were obtained from twelve transcriptome libraries via the Illumina Hiseq X platform, and the differentially expressed genes in the ink sac and brain tissues were identified respectively. Multiple upregulated genes in the ink sac were involved in cation transporter activity. Besides, an autocrine/paracrine factor wnt10b like and two important transcription factors (homeobox 1 and Hes-1-b-like) were also significantly upregulated in the ink sac. Moreover, a neuronal nitric oxide synthase (nNOS) was significantly downregulated in the brain. The findings from this study provide an important transcriptomic resource for discovering critical genes related to inking behavior of S. inermis, providing a basis for developing potential methods for protecting S. inermis from intensive inking.

Objective To examine the predictive value of intrinsic capacity on one-year incident adverse outcomes among community-dwelling older adults. Methods A total of 756 community-dwelling older adults aged ≥ 60 years were followed up after 1 year. Intrinsic capacity was assessed using the revised integrated care for older people screening tool. Adverse outcomes included incident disability, recurrent falls, hospitalization, emergency department visits, and poor quality of life. Multivariate logistic regression models were performed to evaluate the predictive value of intrinsic capacity domains on adverse outcomes. Results Cognitive decline, limited mobility, visual impairment and depressive symptoms predicted incident disability. Visual impairment predicted recurrent falls. Cognitive decline and limited mobility predicted emergency department visits. Limited mobility predicted poor quality of life. Discussion Intrinsic capacity could predict incident adverse outcomes among community-dwelling older adults. Assessing intrinsic capacity would facilitate early identification of older adults at high risk of adverse outcomes and prompt targeted interventions.

Background: Although numerous studies have suggested that the gradually increasing selective preference for positive information over negative information in older adults depends on cognitive control processes, few have reported the characteristics of different attention stages in the emotional processing of older individuals. The present study used a real-time eye-tracking technique to disentangle the attentional engagement and disengagement processes involved in age-related positivity effect (PE).Methods: Eye movement data from a spatial-cueing task were obtained for 32 older and 32 younger healthy participants. The spatial-cueing task with varied cognitive loads appeared to be an effective way to explore the role of cognitive control during the attention engagement and disengagement stages of emotion processing.Results: Compared with younger adults, older participants showed more positive gaze preferences when cognitive resources were sufficient for face processing at the attention engagement stage. However, the age-related PE was not observed at the attention disengagement stage because older adults had more difficulty disengaging from fearful faces than did the younger adults due to the consumption of attention by the explicit target judgment.Conclusion: The present study highlights how cognitive control moderates positive gaze preferences at different attention processing stages. These findings may have far-reaching implications for understanding, preventing, and intervening in unsuccessful aging and, thus, in promoting active and healthy aging.

BackgroundIncreasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet.MethodsPlasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed.ResultsThirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio.ConclusionOur findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.

The complete mitogenome sequence of the ruby dragonet Synchiropus sycorax was first determined using next-generation sequencing strategy in this study. The circle genome was 16,656 bp in length and consisted of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. The mitochondrial gene arrangement of S. sycorax is similar to those of most other fish species. Results from neighbor-joining phylogenetic analysis showed that S. sycorax clustered with S. splendidus and other species of the family Callionymidae. This study will be valuable for phylogenetic analysis of the genus Synchiropus and the other genera of the order Syngnathiformes.

Objective To examine the moderating effects of age and sex in the role of functional disability as a mediator between pain and depression. Methods Participants were 1917 community-dwelling older adults from Jinan, China. Data were collected on pain intensity, functional disability in activities of daily living and instrumental activities of daily living, depressive symptoms and covariates. Results Functional disability partially mediated the relationship between pain intensity and depressive symptoms (estimate = 0.015, SE = 0.007, 95% CI [0.004, 0.030]). Age and sex moderated both the direct and indirect effect of the mediation model. The mediating effect of functional disability was significant in the old-old men, young-old men, and young-old women, but not in the old-old women. Conclusions Interventions should target both pain and pain-related functional disability to improve their emotional well-being among community-dwelling older adults. Importantly, strategies should be tailored across different age and sex groups to improve their effectiveness.

Disturbed intrauterine development increases the risk of renal disease. Various studies have reported that Notch signalling plays a significant role in kidney development and kidney diseases. A disintegrin and metalloproteinase domain 10 (ADAM10), an upstream protease of the Notch pathway, is also reportedly involved in renal fibrosis. However, how ADAM10 interacts with the Notch pathway and causes renal fibrosis is not fully understood. In this study, using a prenatal chlorpyrifos (CPF) exposure mouse model, we investigated the role of the ADAM10/Notch axis in kidney development and fibrosis. We found that prenatal CPF‐exposure mice presented overexpression of Adam10, Notch1 and Notch2, and led to premature depletion of Six2+ nephron progenitors and ectopic formation of proximal tubules (PTs) in the embryonic kidney. These abnormal phenotypic changes persisted in mature kidneys due to the continuous activation of ADAM10/Notch and showed aggravated renal fibrosis in adults. Finally, both ADAM10 and NOTCH2 expression were positively correlated with the degree of renal interstitial fibrosis in IgA nephropathy patients, and increased ADAM10 expression was negatively correlated with decreased kidney function evaluated by serum creatinine, cystatin C, and estimated glomerular filtration rate. Regression analysis also indicated that ADAM10 expression was an independent risk factor for fibrosis in IgAN. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

We aimed to compare the diagnostic test accuracy (DTA) of six frailty screening tools against comprehensive geriatric assessment (CGA) in the community. A total of 1177 community-dwelling older people were recruited. Frailty was assessed by purely physical tools including Physical Frailty Phenotype (PFP), FRAIL (fatigue, resistance, ambulation, illness and loss of weight), Study of Osteoporotic Fracture (SOF), and multidimensional tools including Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI) and Comprehensive Frailty Assessment Instrument (CFAI). The receiver operating characteristic curve analyses were performed. The GFI, TFI and CFAI [areas under the curve (AUCs): 0.78-0.80] had better diagnostic accuracy than SOF, PFP and FRAIL (AUCs: 0.69-0.72) (χ2: 6.37-26.76, P

Podocyte injury is an important cause of proteinuria. Angiopoietin-like protein 4 (Angptl4) is a secreted glycoprotein and has a role in proteinuria. However, the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified. In this study, we used lipopolysaccharide (LPS)-induced mice and cultured podocytes as podocyte injury models. Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro. Furthermore, we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement, reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury. In addition, we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes. Moreover, inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro. Taken together, our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes, which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.

Organ dysfunction caused by sepsis is life-threatening and results in high mortality. Therapeutic options for sepsis are limited. Pathogenic factors are considered as components of environmental pressure that modify DNA methylation patterns thereby enhancing disease progression. Here, we found that sepsis patients exhibited higher levels of genomic DNA methylation patterns and hypermethylated genes associated with the NF-kB signaling pathway. Therefore, we hypothesized that a DNA methyl transferase inhibitor, Decitabine, may mitigate inflammation and improve survival by inhibiting the NF-κB signaling pathway. To test the hypothesis, mice challenged with caecal ligation and puncture (CLP) were subcutaneously injected with Decitabine solution (0.5, 1, and 1.5 mg/kg) 2 h following operation. Our results indicated that Decitabine reduces DNA methyltransferases (DNMTs), attenuates NF-κB activation, downregulates inflammatory cytokine levels, and inhibits the progression of sepsis. Thus, DNA methylation may be indispensable for sepsis and serve as a predicting factor. The use of Decitabine could represent a novel strategy in the treatment of sepsis.