Predicting Bloodstream Infection in High-risk Groups of Liver Failure Patients with Artificial Liver Support System.

Background: Liver failure is a rare, life-threatening disease that has a high mortality rate and affects many organ systems. Bloodstream bacterial infection has played a key role in liver failure patients with plasma exchange-centered artificial liver support systems, but the predicted risk factors of infection have not been fully understood. Objective: We aimed to predict bloodstream bacterial infection in high-risk groups of liver failure patients during a plasma exchange-centered artificial liver support system. Design: This was a prospective cohort study. Setting: This study was performed in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School. Participants: 118 liver failure patients with plasma exchange-centered artificial liver support system therapy from Nanjing Drum Tower Hospital from November 2019 to November 2020 were selected. Interventions: We used a stepwise binary logistic regression model to select the optimal risk factors of infection with minimum Akaike information criterion, and the Nomogram prognostic model for bloodstream infection was constructed for visualization. Primary Outcome Measures: Risk factors of bloodstream infection (2) predictive accuracy of the constructed nomogram model. Results: Among the 118 liver failure patients, 22 (18.64%) were diagnosed with bloodstream bacterial infection. The univariable and multivariate logistic regression analyses suggested that culture level, glucocorticoids use, number of punctures, blood platelet counts, white blood cell counts, and indwelling catheter time were the sex predictors of bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system (P = .042, P = .013, P = .025, P = .003, P = .024 and P = .026). The nomogram predictive model was established with high prediction accuracy, of which the area under the curve was 0.935 (95% confidence interval: 0.884-0.986), the sensitivity was 0.955, and the specificity was 0.854. Conclusion: The constructed nomogram prognostic model can recognize the risk factors and accurately predict bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system.

Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived ß cells.

Human pluripotent stem cell-derived ß cells (hPSC-ß cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-ß cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-ß cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-ß cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for ß cell maturation. Limiting intracellular accumulation of ceramides in hPSC-ß cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic ß cells and highlight the importance of ceramide homeostasis in function acquisition.

NAFLD is associated with less severe liver fibrosis in chronic hepatitis B: A multi-center, retrospective study.

INTRODUCTION AND OBJECTIVES: Chronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. PATIENTS AND METHODS: Treatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. RESULTS: A total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. CONCLUSIONS: NAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. OF THE STUDY/TRIAL: NCT03097952.

Effect of raw material frozen storage on physicochemical properties and flavor compounds of fermented mandarin fish (Siniperca chuatsi).

Frozen mandarin fish (MF) is utilized for preparation fermented MF. However, how raw material (RM) affects the quality and flavor of fermented MF is unclear. This study investigated the impact and mechanism of RM frozen storage on the microstructure, texture, water distribution, and flavor of fermented MF by light microscopy, texture profile analysis, low-field nuclear magnetic resonance, gas chromatography-ion mobility spectrometry, and multivariate analysis. With increasing RM frozen storage time, both frozen MF and frozen-based fermented MF decreased in muscle fiber density while increased in muscle fiber diameter. Additionally, RM frozen storage exhibited a significant impact on the water distribution of frozen MF, while no obvious effect on that of frozen-based fermented MF. Seven odorant (2-methyl-1-propanol, 3-hydroxy-2-butanone, 2,3-butanedione, hexanal-D, ethyl acetate-D, 3-pentanone, and acetone) were shown as potential markers to distinguish fermented MF. This study could provide a theoretical basis for the production of high-quality frozen-based fermented MF.

Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets.

Human pluripotent stem cell-derived islets (hPSC islets) are a promising alternative to primary human islets for the treatment of insulin-deficient diabetes. We previously demonstrated the feasibility of this approach in nonhuman primates; however, the therapeutic effects of hPSC islets can be limited by the maladaptive processes at the transplantation site. Here, we demonstrate successful implantation of hPSC-derived islets in a new transplantation site in the abdomen, the subanterior rectus sheath, in eight nonhuman primates (five male and three female). In this proof-of-principle study, we find that hPSC islets survive and gradually mature after transplantation, leading to improved glycemic control in diabetic primates. Notably, C-peptide secretion responds to meal challenge from 6 weeks post-transplantation (wpt), with stimulation indices comparable to those of native islets. The average post-prandial C-peptide level reaches approximately 2.0 ng ml-1 from 8 wpt, which is five times higher than the peak value we previously obtained after portal vein infusion of hPSC islets and was associated with a decrease of glycated hemoglobin levels by 44% at 12 wpt. Although additional studies in larger cohorts involving long-term follow-up of transplants are needed, our results indicate that the subanterior rectus sheath supports functional maturation and maintenance of hPSC islets, suggesting that it warrants further exploration as a transplantation target site in the context of for hPSC-based cell-replacement therapies.

Overexpression of ERCC6L correlates with poor prognosis and confers malignant phenotypes of lung adenocarcinoma.

Excision repair cross­complementation group 6 like (ERCC6L) has been reported to be upregulated in a variety of malignant tumors and plays a critical oncogenic role. However, the role and molecular mechanism of ERCC6L in lung adenocarcinoma (LUAD) remain unclear, and were therefore investigated in the present study. Clinical data of patients with LUAD were obtained and bioinformatics analysis was performed to investigate the expression characteristics, prognostic value, and biological function of ERCC6L. In addition, cell function experiments were performed to detect the effect of ERCC6L silencing on the biological behavior of LUAD cells. The results revealed that ERCC6L expression was significantly higher in LUAD tissues vs. normal lung tissues and closely associated with nodal invasion, advanced clinical stage and survival in LUAD. Overexpression of ERCC6L was an independent prognostic biomarker of overall survival, progression­free interval, and disease­specific survival in patients with LUAD. DNA amplification and low methylation levels of ERCC6L suggested regulation at both the genetic and epigenetic levels. The most significant positive genes co­expressed with ERCC6L were mainly enriched in the cell cycle signaling pathway. The major functions of ERCC6L in LUAD cells were positively correlated with the cell cycle, DNA damage, DNA repair, proliferation, invasion and epithelial­mesenchymal transition (EMT). Knockdown of ERCC6L inhibited the proliferative, migratory and invasive abilities of A549 and PC9 cells. It also promoted cell apoptosis, and led to cell cycle arrest in the S phase. ERCC6L may regulate the EMT process through the Wnt/ß­catenin and Wnt/Notch 3 signaling pathways, thus regulating the tumorigenesis and progression of LUAD. The overexpression of ERCC6L may be a biological indicator for the diagnosis and prognosis of LUAD. ERCC6L may be a novel molecular target for the treatment of lung cancer.

Transmuscular quadratus lumborum block for postoperative pain and recovery after laparoscopic adrenalectomy: a randomized controlled trial.

BACKGROUND: To investigate the role of transmuscular quadratus lumborum block (TMQLB) for postoperative pain control, patient satisfaction and recovery in laparoscopic adrenalectomy. METHODS: Seventy-two patients aged between 18 and 70 years with an ASA I-II and scheduled for laparoscopic adrenalectomy were randomized to receive a single-shot TMQLB with 0.4 ml/kg 0.5 % ropivacaine or 0.4 ml/kg 0.9 % saline as placebo. The primary endpoint was pain on movement at 12 h after surgery evaluated by the numeric rating scale (NRS, 0-10). P-values < 0.05 was considered statistically significant. The secondary outcomes included pain at rest and pain on movement evaluated by the NRS, and postoperative recovery related parameters. RESULTS: NRS on movement at 12 h after surgery was lower in the TMQLB group compared with the control (median 2 vs. 3, p = 0.024). Intraoperative fentanyl consumption was lower in the TMQLB group (247.08 ± 63.54 vs. 285.44 ± 74.70, p = 0.022). The rate of using postoperative rescue tramadol was also lower in the TMQLB group (5.6 vs. 27.8 %, p = 0.027). Similar incidences of nausea and vomiting were observed (11.1 vs. 25 %, p = 0.220). Patient satisfaction of pain service was better in the TMQLB group (83.3 vs. 25 %, p < 0.001) with shorter time to ambulation (16.5 vs. 21 h, p = 0.004) and flatus (18.5 vs. 23.5 h, p = 0.006). CONCLUSIONS: TMQLB showed better control of postoperative pain on movement for laparoscopic adrenalectomy with improved patients' satisfaction of anesthesia, shorter time to ambulation and flatus. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov ( NCT03942237 ; registration date: 08/05/2019; enrollment date: 10/05/2019).

Effects of oxidative modification on the functional, conformational and gelling properties of myofibrillar proteins from Culter alburnus.

Protein oxidation is a critical process in the deterioration and spoilage of fish and related commodities during processing and storage. In this study, the hydroxyl radical generation system (HRGS) was used to simulate the effect of oxidation on the functional, conformational and gelling properties of topmouth culter (Culter alburnus) myofibrillar proteins (MP). Additionally, the effects of oxidation on the gel-forming abilities of MP were also systematically analyzed from the perspective of intermolecular interaction forces. Oxidation was shown to decrease the total sulfhydryl content, increase the surface hydrophobicity, and induce conformational changes in MP. Rheological analysis showed that oxidation reduced the gel strength. Water holding capacity (WHC) and low-field nuclear magnetic resonance (LF-NMR) analyses showed that low oxidation could enhance water binding of protein matrix, while high-degree oxidation could substantially reduce the gelling properties of MP. The selective solubility of MP gel proved that oxidation could reduce the content of ionic and hydrogen bonds and increase hydrophobic interactions. All the results indicate that oxidation could alter the intermolecular interactions between protein-protein and protein-water molecules, due to irregular unfolding and inhibition of the cross-linking of amino acid side chains, leading to reduction in the quality and function of fish and related products.

Characteristics of hepatitis B core antibody level in the natural history of chronic hepatitis B.

OBJECTIVE: We aimed to analyze serum antibody to hepatitis B core antigen (anti-HBc) level during different immunological phases in the natural history of patients with chronic hepatitis B (CHB). METHODS: Serum anti-HBc levels in the immune tolerant (IT), immune clearance (IC), low replicative (LR), and HBeAg negative hepatitis (ENH) phases from 634 treatment-naïve CHB patients were measured and compared between phases and with other serum markers. RESULTS: Median serum anti-HBc levels were different between the phases of CHB. Serum anti-HBc level was highest in the ENH phase and lowest in the IT phase. Serum anti-HBc level correlated only with ALT in the IC phase (r = 0.248, p < 0.001). The area under the receiver operating characteristic curve (AUC) of anti-HBc at a cutoff value of 9.03 S/CO for differentiation of IT and IC phases was 0.689 (sensitivity 74.03%, specificity 60.23%). The AUC for differentiation of LR and ENH phases was 0.751 (sensitivity 68.32%, specificity 70.53%) at a cutoff value of 9.74 S/CO for anti-HBc. CONCLUSIONS: Serum anti-HBc levels were significantly different across different phases of CHB and were associated with hepatitis activities.

Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection.

Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.

Irrationality of Allogeneic Red Blood Cell Transfusion in Intraoperative Cell Salvage Patients: a Retrospective Analysis.

Objective Although intraoperative cell salvage (ICS) has been widely used to reduce the demand for allogeneic blood transfusion, patients who use ICS approach still have not completely avoided chances of blood transfusion. This study aims to investigate the rate of allogeneic red blood cell(RBC) transfusion in patients receiving ICS, and to evaluate irrationality of allogeneic RBC transfusion and its risk factors.Methods Medical records of all patients associated with ICS approach from January 2013 to July 2014 were retrospectively reviewed. Theoretical hemoglobin level after reinfusion of salvaged RBC at the end of operations was estimated. Irrational transfusion was defined as initiating allogeneic transfusion with theoretical hemoglobin above 100 g/L. The clinical variables, including the surgical department, gender, age, body weight, ratio of blood loss to estimated blood volume(EBV), salvaged blood volume and preoperative hemoglobin level were subsequently compared between patients who received rational transfusion and those did not. Logistic regression was performed to identify the risk factors for irrationality of allogeneic RBC transfusion in these patients.Results Of 1487 patients with ICS approach in this study, the rate of allogeneic RBC transfusion was 31.4%(467/1487), and the rate of irrational allogeneic RBC transfusion was 26.0% (341/1313). Patients with irrational transfusion were younger (t=4.656, P<0.001), with lower body weight (t=3.910, P<0.001) and slightly lower preoperative HGB level (t=2.822, P=0.005) than those with rational transfusion, but had significantly larger salvaged blood volume (U=-10.926, P<0.001) and higher ratio of blood loss to EBV (U=-17.067, P<0.001), disregarding whether they preoperatively met anemia criteria or not (U=-1.396, P=0.163). Preoperative hemoglobin level (OR=1.975, P=0.005) and the ratio of blood loss/EBV (OR=5.392, P<0.001) were independent risk factors leading to the irrational allogeneic RBC transfusion.Conclusions The irrationality of allogeneic RBC transfusion existed in ICS patients, which may be associated with the preoperative hemoglobin level and the ratio of blood loss to EBV. Determining the HGB levels before transfusion is required to avoid unnecessary blood administration. Doctors should keep their knowledge in blood management updated and improve their awareness of rational transfusion for a better patients care.

Identification of a differentially-expressed gene in fatty liver of overfeeding geese.

In response to overfeeding, geese develop fatty liver. To understand the fattening mechanism, mRNA differential display reverse transcription PCR was used to study the gene expression differences between French Landes grey geese and Xupu white geese in conditions of overfeeding and normal feeding. One gene was found to be up-regulated in the fatty liver in both breeds, and it has a 1797 bp cDNA with 83% identity to chicken SELENBP1. The sequence analysis revealed that its open reading frame of 1413 bp encodes a protein of 471 amino acids, which contains a putative conserved domain of 56 kDa selenium binding protein with high homology to its homologues of chicken (95%), rat (86%), mouse (84%), human (86%), monkey (86%), dog (86%), and cattle (86%). The function of this protein has been briefly reviewed based on published information. In tissue expression analysis, the expression of geese SELENBP1 mRNA was found to be higher in liver or kidney than in other tested tissues. The results showed that overfeeding could increase the mRNA expression level of geese SELENBP1.

[The effect of local vibration on blood-lipids and whole blood viscosity].

OBJECTIVE: To study the effects of local vibration on blood-lipids and whole blood viscosity. METHODS: The total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), whole blood viscosity, apolipoprotein (Apo-), red blood cell (RBC), platelet (PLT), mean corpuscular volume (MCV), serum-protein, postprandial blood sugar (PBS), and serum-protein of experimental and control workers were detected. The difference of the means and abnormal rates of two groups were compared. RESULTS: The means of TG, TC, HDL in exposed group [(1.01 +/- 0.85), (3.25 +/- 0.61), (1.14 +/- 0.20) mmol/L respectively] were significantly lower than that of control group [(1.89 +/- 1.47), (3.87 +/- 0.82), (1.22 +/- 0.26) mmol/L, respectively, P < 0.01 or P < 0.05]. Apo-A was also decreased [(1.13 +/- 0.29) g/L vs (1.23 +/- 0.16) g/L, P < 0.01]. The mean of whole blood viscosity were significantly increased in exposed group [(2.76 +/- 0.42) mPa.s vs (2.54 +/- 0.33) mPa.s, P < 0.01]. The abnormal rate of Apo-A was significantly higher in exposed group (23.30%) than that in control (4.50%, P < 0.01). CONCLUSION: Local vibration may induce decrease in blood lipids, increase in blood viscosity and changes in some other blood parameters.