Summary
Background
Inflammation plays a vital role in liver cirrhosis progression and prognosis.
Aim
To investigate the prognostic significance of inflammatory response markers in decompensated ...cirrhotic patients without acute‐on‐chronic liver failure (ACLF).
Methods
Independent predictors were identified using multivariate Cox model and then assembled into a nomogram to predict survival. Concordance index (C‐index) and time‐dependent receiver operating characteristics (td‐ROC) analysis were adopted to evaluate and compare the performance of nomogram, model for end‐stage liver disease (MELD) scores, MELD‐Na and Chronic Liver Failure‐consortium score for acute decompensated (CLIF‐C ADs).
Results
A total of 902 decompensated cirrhotic patients with different aetiologies were enrolled, with 6‐month, 1‐year and 3‐year mortality of 18.6%, 24.4% and 34.8%, respectively. The cut‐off values for neutrophil‐to‐lymphocyte ratio (NLR) and lymphocyte‐to‐monocyte ratio (LMR) determined by X‐tile program were 5.7 and 1.1 respectively. Patients with NLR>5.7 or LMR≤1.1 had significantly higher mortality (P < 0.001). Independent factors derived from multivariable Cox analysis of development cohort to predict mortality were age, NLR and LMR (hazard ratio (HR): 1.064, 95% confidence interval (CI): 1.045–1.084, P < 0.001; HR: 1.124, 95%CI: 1.091–1.158, P < 0.001; HR: 0.794, 95%CI: 0.702–0.898, P < 0.001, respectively). The C‐indexes of nomogram were higher than that of MELD score, MELD‐Na and CLIF‐C ADs for predicting survival. The tdROC and decision curves showed that nomogram was superior to MELD score, MELD‐Na and CLIF‐C ADs. Similar results were observed in validation cohort.
Conclusion
The proposed nomogram with neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐monocyte ratio resulted in accurate prognostic prediction for decompensated cirrhotic patients without ACLF.
Linked ContentThis article is linked to Forest and Cai and Shi et al papers. To view these articles visit https://doi.org/10.1111/apt.14183 and https://doi.org/10.1111/apt.14208.
The COVID‐19 coronavirus is now spreading worldwide. Its pathogen, SARS‐CoV‐2, has been shown to use angiotensin‐converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute ...respiratory syndrome coronavirus (SARS‐CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age‐dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. A shockingly common enrichment of viral infection pathways was found among ACE2 anti‐expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID‐19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.
This study revealed the negative correlation of high basal ACE2 level with CoVID‐19 severity/fatality at the population level and its anticorrelation with virus infection pathway expression levels, upregulation by sex hormones and suppression by inflammatory cytokine at the molecular level.
Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of ...linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.
Abstract An effective method for the 3D porous scaffold design of human tissue is presented based on a hybrid method of distance field and triply periodic minimal surface (TPMS). By the creative ...application of traditional distance field algorithm into the Boolean operations of the anatomical model and TPMS-based unit cell library, an almost defects free porous scaffolds having the complicated micro-structure and high quality external surface faithful to a specific anatomic model can be easily obtained without the difficult and time-consuming trimming and re-meshing processes. After generating the distance fields for the given tissue model and required internal micro-structure, a series of simple modifications in distance fields enable us to obtain a complex porous scaffold. Experimental results show that the proposed scaffold design method has the potential to combine the perfectly interconnected pore networks based on the TPMS unit cell libraries and the given external geometry in a consistent framework irrespective of the complexity of the models.
In mice, a high-fat diet (HFD) induces obesity, insulin resistance and myostatin production. We tested whether inhibition of myostatin in mice can reverse these HFD-induced abnormalities.
C57BL/6 ...mice were fed a HFD for 16 weeks including the final 4 weeks some mice were treated with an anti-myostatin peptibody. Body composition, the respiratory exchange ratio plus glucose and insulin tolerance tests were examined. Myostatin knock down in C2C12 cells was performed using small hairpin RNA lentivirus. Adipose tissue-derived stem cells were cultured to measure their responses to conditioned media from C2C12 cells lacking myostatin, or to recombinant myostatin or irisin. Isolated peritoneal macrophages were treated with myostatin or irisin to determine whether myostatin or irisin induce inflammatory mechanisms.
In HFD-fed mice, peptibody treatment stimulated muscle growth and improved insulin resistance. The improved glucose and insulin tolerances were confirmed when we found increased muscle expression of p-Akt and the glucose transporter, Glut4. In HFD-fed mice, the peptibody suppressed macrophage infiltration and the expression of proinflammatory cytokines in both the muscle and adipocytes. Inhibition of myostatin caused the conversion of white (WAT) to brown adipose tissue, whereas stimulating fatty acid oxidation and increasing energy expenditure. The related mechanism is a muscle-to-fat cross talk mediated by irisin. Myostatin inhibition increased peroxisome proliferator-activated receptor gamma, coactivator 1α expression and irisin production in the muscle. Irisin then stimulated WAT browning. Irisin also suppresses inflammation and stimulates macrophage polarization from M1 to M2 types.
These results uncover a metabolic pathway from an increase in myostatin that suppresses irisin leading to the activation of inflammatory cytokines and insulin resistance. Thus, myostatin is a potential therapeutic target to treat insulin resistance of type II diabetes as well as the shortage of brown/beige fat in obesity.
SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules. This review discusses the growing ...number of applications of SuFEx, which can be found in nearly all areas of modern chemistry; from drug discovery to materials science.
Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of ...organismal longevity. Caenorhabditis elegans is a well‐established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue‐specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age‐induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue‐specific factors, including irx‐1 and myrf‐2, which control the integrity of the intestinal barrier and sarcomere structure during ageing respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue‐specific transcriptomic profiling during ageing, which can serve as a resource to the field.
Synopsis
Whether organismal ageing is associated with specific changes in different tissues and organs remains poorly addressed. Here, dissection and transcriptomic analyses of diverse C. elegans tissues provides insight into the disting ageing trajectories and regulators in each of them.
Five major somatic tissues—nervous system, hypodermis, intestine, coelomocyte and body all muscle ‐ undergo distinct transcriptomic changes during C. elegans ageing.
Tissue‐specific changes between young and old worms are more pronounced than common changes in different tissues.
Ageing regulates similar biological processes with different gene sets and regulators across tissues.
Transcription factors irx‐1/IRX and myrf‐2/MYRF control ageing of intestine and body wall muscle, respectively.
Expression profiling of worm ageing uncovers common and organ‐specific molecular pathways involved in health deterioration.
Conventional gene expression studies analyze multiple cells simultaneously or single cells, for which the exact in vivo or in situ position is unknown. Although cellular heterogeneity can be ...discerned when analyzing single cells, any spatially defined attributes that underpin the heterogeneous nature of the cells cannot be identified. Here, we describe how to use Geo-seq, a method that combines laser capture microdissection (LCM) and single-cell RNA-seq technology. The combination of these two methods enables the elucidation of cellular heterogeneity and spatial variance simultaneously. The Geo-seq protocol allows the profiling of transcriptome information from only a small number cells and retains their native spatial information. This protocol has wide potential applications to address biological and pathological questions of cellular properties such as prospective cell fates, biological function and the gene regulatory network. Geo-seq has been applied to investigate the spatial transcriptome of mouse early embryo, mouse brain, and pathological liver and sperm tissues. The entire protocol from tissue collection and microdissection to sequencing requires ∼5 d, Data analysis takes another 1 or 2 weeks, depending on the amount of data and the speed of the processor.
During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state
. Concurrently, germ layers are ...formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation
. The regionalization of cell fates preceding the formation of the basic body plan-the mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational study-is conserved in vertebrate embryos
. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptome of cell populations at defined positions in the germ layers during development from pre- to late-gastrulation stages. This spatiotemporal transcriptome provides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of Hippo-Yap signalling in germ-layer development and reveals the contribution of visceral endoderm to the endoderm in the early mouse embryo.
The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
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