Background
Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important ...role. The aim of this study was to evaluate whether postoperative infective complications influence long‐term survival after liver resection for hepatocellular carcinoma (HCC).
Methods
Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence‐free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection.
Results
Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021).
Conclusion
Postoperative infective complications decreased long‐term OS and RFS in patients treated with liver resection for HCC.
From a multi‐institutional database, 2442 patients who underwent resection with curative intent for hepatocellular carcinoma between 2003 and 2016 were analysed retrospectively. Among them, 332 patients (13·6 per cent) had postoperative infective complications within 30 days after surgery. Multivariable Cox regression revealed that postoperative infective complications decreased long‐term overall and recurrence‐free survival after liver resection for hepatocellular carcinoma.
Complications decrease long‐term overall survival
Micro-RNAs (miRNAs) are a class of approximately 22-nucleotide non-coding RNAs expressed in multicellular organisms. They are first transcribed in a similar manner to pre-mRNAs. The transcripts then ...go through a series of processing steps, including endonucleolytic cleavage, nuclear export and a strand selection procedure, to yield the single-stranded mature miRNA products. The transcription and processing of miRNAs determines the abundance and the sequence of mature miRNAs and has important implications for the function of miRNAs.
Summary
The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous ...microorganisms have co‐evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Summary
We explored the association between gut microbiota composition and bone mineral loss in Chinese elderly people by high-throughput 16S ribosomal RNA (rRNA) gene sequencing. Compared with ...controls, a smaller number of operational taxonomic units (OTUs), several taxa with altered abundance, and specific functional pathways were found in individuals with low-bone mineral density (BMD).
Introduction
Gut microbiota plays important roles in human health and associates with a number of diseases. However, few studies explored its association with bone mineral loss in human.
Methods
We collected 102 fecal samples from each eligible individual belonging to low-BMD and control groups for high-throughput 16S rRNA gene sequencing.
Results
The low-BMD individuals had a smaller number of OTUs and bacterial taxa at each level. At the phylum level, Bacteroidetes were more abundant in the low-BMD group; Firmicutes were enriched in the control group; Firmicutes and Actinobacteria positively correlated and Bacteroidetes negatively correlated with the BMD and T-score in all subjects. At the family level, the abundance of Lachnospiraceae in low-BMD individuals reduced and positively correlated with BMD and T-score; meanwhile, BMD increased with increasing Bifidobacteriaceae. At the genus level, low-BMD individuals had decreased proportions of
Roseburia
compared with control ones (
P
< 0.05).
Roseburia
,
Bifidobacterium
, and
Lactobacillus
positively correlated with BMD and T-score. Furthermore, BMD increased with rising abundance of
Bifidobacterium
. Functional prediction revealed that 93 metabolic pathways significantly differed between the two groups (FDR-corrected
P
< 0.05). Most pathways, especially pathways related to LPS biosynthesis, were more abundant in low-BMD individuals than in control ones.
Conclusions
Several taxa with altered abundance and specific functional pathways were discovered in low-BMD individuals. Our findings provide novel epidemiologic evidence to elucidate the underlying microbiota-relevant mechanism in bone mineral loss and osteoporosis.
Human exposure to perfluorochemicals (PFCs) has attracted mounting attention due to their potential harmful effects. Breathing, dietary intake, and drinking are believed to be the main routes for PFC ...entering into human body. Thus, we profiled PFC compositions and concentrations in indoor air and dust, food, and drinking water with detailed analysis of literature data published after 2010. Concentrations of PFCs in air and dust samples collected from home, office, and vehicle were outlined. The results showed that neutral PFCs (e.g., fluorotelomer alcohols (FTOHs) and perfluorooctane sulfonamide ethanols (FOSEs)) should be given attention in addition to PFOS and PFOA. We summarized PFC concentrations in various food items, including vegetables, dairy products, beverages, eggs, meat products, fish, and shellfish. We showed that humans are subject to the dietary PFC exposure mostly through fish and shellfish consumption. Concentrations of PFCs in different drinking water samples collected from various countries were analyzed. Well water and tap water contained relatively higher PFC concentrations than other types of drinking water. Furthermore, PFC contamination in drinking water was influenced by the techniques for drinking water treatment and bottle-originating pollution.
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•Neutral PFCs are dominant in indoor air and dust.•Dietary PFC exposure is mostly through fish, shellfish and meat consumption.•Well water and tap water contain relatively higher PFC concentrations than other types of drinking water.
Growth performance, digestive and absorptive capacities and target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and eIF4E‐binding protein (4E‐BP) gene expression in the hepatopancreas and ...intestine of juvenile grass carp (Ctenopharyngodon idellus) fed graded ratios of dietary alpha‐linolenic acid/linoleic acid (ALA/LNA) (0.01, 0.34, 0.68, 1.03, 1.41, 1.76 and 2.15) for 60 days were investigated. The results showed that ALA/LNA ratio of 1.03 significantly improved (i) per cent weight gain (PWG) and feed efficiency, (ii) hepatopancreatic trypsin, chymotrypsin, lipase, amylase and intestinal creatine kinase (CK) activities, (iii) hepatopancreatic trypsinogen‐2 and chymotrypsinogen mRNA levels. Meanwhile, fish fed with ALA/LNA ratio of 0.68 significantly enhanced, (iv) Na+/K+‐ATPase and γ‐glutamyl transpeptidase activities in whole intestine, and alkaline phosphatase activities in the proximal intestine (PI) and distal intestine, (v) amylase, intestinal Na+/K+‐ATPase alpha‐subunit isoform 1, Na+/K+‐ATPase alpha‐subunit isoform 8 and CK mRNA abundances, (vi) TOR and S6K1 gene expression in the hepatopancreas and intestine of juvenile grass carp. Based on the quadratic regression analysis of PWG, cholecystokinin and leptin contents in the PI, optimal dietary ALA/LNA ratio of juvenile grass carp (8.78–72.00 g) was estimated to be 1.08, 1.19 and 1.05, respectively.
Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that ...recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1β and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins), as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of NEK7, caspase-1 activation and IL-1β release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasomes. NLRP3-activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high-molecular-mass NLRP3-NEK7 complex, which, along with ASC oligomerization and ASC speck formation, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed that NEK7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation.
The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut ...dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut.
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