Construction of a novel prognostic scoring model for HBV-ACLF liver failure based on dynamic data.

Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure.

BACKGROUND: The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. METHODS: Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. RESULTS: THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis. CONCLUSIONS: THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies.

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC.

BACKGROUND: Long noncoding RNAs (lncRNAs) are implicated in the tumor immunology of hepatocellular carcinoma (HCC). METHODS: HCC mRNA and lncRNA expression profiles were used to extract immune-related genes with the ImmPort database, and immune-related lncRNAs with the ImmLnc algorithm. The MOVICS package was used to cluster immune-related mRNA, immune-related lncRNA, gene mutation and methylation data on HCC from the TCGA. GEO and ICGC datasets were used to validate the model. Data from single-cell sequencing was used to determine the expression of genes from the model in various immune cell types. RESULTS: With this model, the area under the curve (AUC) for 1-, 3- and 5-year survival of HCC patients was 0.862, 0.869 and 0.912, respectively. Single-cell sequencing showed EREG was significantly expressed in a variety of immune cell types. Knockdown of the EREG target gene resulted in significant anti-apoptosis, pro-proliferation and pro-migration effects in HepG2 and HUH7 cells. Moreover, serum and liver tissue EREG levels in HCC patients were significantly higher than those of healthy control patients. CONCLUSION: We built a prognostic model with good accuracy for predicting HCC patient survival. EREG is a potential immunotherapeutic target and a promising prognostic biomarker.

Effects of Protection Time on Infection of Rice Panicle Blast.

Panicle blast, caused by Magnaporthe oryzae, is a destructive disease of rice worldwide. Clarifying the susceptibility of rice panicles at different stages is of great significance for effective disease management. Field experiments were conducted in two paddy fields at Wuyuan County in 2016 and 2017 to determine the effects of head covering and its timing on the infection of rice panicle blast. Results revealed that panicle blast was reduced significantly by covering rice heads with sulfuric acid paper bags, regardless of the covering time, ranging from initial heading to 15 days afterward, suggesting that rice panicles could be infected by blast pathogen even 15 days after initial heading. Panicle blast incidence was also found to be significantly influenced by plant dates, with higher panicle blast incidence observed in plots planted on early dates, suggesting adjusting plant dates could help rice panicles escape the infection by blast pathogen. The results from this study also highlighted the importance of cultivars and environmental conditions to panicle blast. In conclusion, besides planting blast-resistant cultivars, it is important to protect rice heads from the initial heading to the early dough stages, and fungicides should be applied according to infection warnings based on host, inoculum, and weather conditions.

Modification on Flower Defects and Electronic Properties of Epitaxial Graphene by Erbium.

Manipulating the topological defects and electronic properties of graphene has been a subject of great interest. In this work, we have investigated the influence of Er predeposition on flower defects and electronic band structures of epitaxial graphene on SiC. It is shown that Er atoms grown on the SiC substrate actually work as an activator to induce flower defect formation with a density of 1.52 × 1012 cm-2 during the graphitization process when the Er coverage is 1.6 ML, about 5 times as much as that of pristine graphene. First-principles calculations demonstrate that Er greatly decreases the formation energy of the flower defect. We have discussed Er promoting effects on flower defect formation as well as its formation mechanism. Scanning tunneling microscopy (STM) and Raman and X-ray photoelectron spectroscopy (XPS) have been utilized to reveal the Er doping effect and its modification to electronic structures of graphene. N-doping enhancement and band gap opening can be observed by using angle-resolved photoemission spectroscopy (ARPES). With Er coverage increasing from 0 to 1.6 ML, the Dirac point energy decreases from -0.34 to -0.37 eV and the band gap gradually increases from 320 to 360 meV. The opening of the band gap is attributed to the synergistic effect of substitution doping of Er atoms and high-density flower defects.

Terrace-Like 2D Hierarchically Porous Iron/Cobalt Metal-Organic Framework: Ambient Fast Synthesis and Efficient Oxygen Evolution Reaction Application.

It is urgent to design a low-cost electrocatalyst with high activity to enhance the efficiency of oxygen evolution reaction (OER), which is limited by the slow four-electron transfer kinetics process. Nevertheless, traditional synthetic methods, including calcination and solvothermal, of the electrocatalysts are high-cost, low-yield, and energy-hogging, which limits their industrial application. Herein, an ambient fast synthetic method is developed to prepare terrace-like Fe/Co bimetal-organic framework (TFC-MOF) electrocatalyst materials in gram scale in 1 h. The method in this paper is designable based on coordination chemistry. Fe and Co ions can coordinate with the carboxyl groups on benzene-1,3,5-tricarboxylic acid (H3 BTC) to form a 2D-MOF structure. Structural characterizations, including SEM, TEM, and XRD are conducted to verify that the TFC-MOF is a terrace-like layered structure with uniform-sized mesoporous, which reduces the adsorption steric hindrance and facilitates the mass and electron transfer efficiency of OER. The TFC-MOF shows low overpotential, 255 mV at a current density of 10 mA cm-2 , and a low Tafel slope of 49.9 mV dec-1 , in an alkaline solution. This work provides a planar coordination strategy to synthesize 2D-MOF OER electrocatalyst on a large scale with low cost and low energy consumption, which will promote its practical OER applications.

Efficacy and safety of vedolizumab in the treatment of patients with inflammatory bowel disease: A systematic review and meta­analysis of randomized controlled trials.

Few studies have thoroughly assessed the efficacy and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD). Therefore, this systematic review and meta-analysis was performed to further evaluate this association. PubMed, Embase, and the Cochrane databases were searched until April 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of VDZ in the treatment of IBD were included. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome using a random effects model. A total of 12 RCTs, including 4,865 patients, met the inclusion criteria. In the induction phase, VDZ was more effective than placebo for patients with ulcerative colitis and Crohn's disease (CD) in clinical remission (RR=2.09; 95% CI=1.66-2.62) and clinical response (RR=1.54; 95% CI=1.34-1.78). In the maintenance therapy group, VDZ reached higher clinical remission (RR=1.98; 95% CI=1.58-2.49) and clinical response (RR=1.78; 95% CI=1.40-2.26) rates compared with the placebo group. VDZ particularly improved clinical remission (RR=2.07; 95% CI=1.48-2.89) and clinical response (RR=1.84; 95% CI=1.54-2.21) in patients with TNF antagonist failure. In terms of corticosteroid-free remission, VDZ was also more effective than placebo in patients with IBD (RR=1.98; 95% CI=1.51-2.59). In Crohn's patients, VDZ was more effective than placebo in terms of mucosal healing (RR=1.78; 95% CI=1.27-2.51). With respect to adverse events, VDZ significantly reduced the risk of IBD exacerbation compared with the placebo (RR=0.60; 95% CI=0.39-0.93; P=0.023). However, when compared with the placebo, VDZ increased the risk of nasopharyngitis in patients with CD (RR=1.77; 95% CI=1.01-3.10; P=0.045). No significant differences in other adverse events were observed. Although there might be underlying risk, such as selection bias, in the present study it can be safely concluded that VDZ is a safe and effective biological agent for IBD, particularly for patients with TNF antagonist failure.

ETS2 alleviates acute-on-chronic liver failure by suppressing excessive inflammation.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with high short-term mortality. The mechanism of the transcription factor ETS2 in ACLF remains unclear. This study aimed to clarify the molecular basis of ETS2 in ACLF pathogenesis. Peripheral blood mononuclear cells from patients with HBV-ACLF (n = 50) were subjected to RNA sequencing. Transcriptome analysis showed that ETS2 expression was significantly higher in ACLF patients than in patients with chronic liver diseases and healthy subjects (all p < 0.001). Area-under-ROC analysis of ETS2 demonstrated high values for the prediction of 28-/90-day mortality in ACLF patients (0.908/0.773). Significantly upregulated signatures of the innate immune response (monocytes/neutrophils/inflammation-related pathways) were observed in ACLF patients with high ETS2 expression. Myeloid-specific ETS2 deficiency in liver failure mice resulted in deterioration of biofunctions and increased expression of pro-inflammatory cytokines (IL-6/IL-1ß/TNF-α). Knockout of ETS2 in macrophages confirmed the downregulation of IL-6 and IL-1ß caused by both HMGB1 and lipopolysaccharide, and an NF-κB inhibitor reversed the suppressive effect of ETS2. ETS2 is a potential prognostic biomarker of ACLF patients that alleviates liver failure by downregulating the HMGB1-/lipopolysaccharide-triggered inflammatory response and may serve as a therapeutic target for ACLF.

Base-Controlled Synthesis of Fluorescent Acridone Derivatives via Formal (4 + 2) Cycloaddition.

A transition-metal-free formal (4 + 2) cycloaddition for the direct assembly of acridone derivatives has been developed from simple and easily accessible o-aminobenzamides and 2-(trimethylsilyl)aryl triflates. The base played an important role in the selective controlled synthesis of N-H and N-aryl acridones. A preliminary study on the fluorescence properties of N-aryl acridones demonstrated that they could be used as fluorescent materials with a broad emission range.

Variations in Growth and Photosynthetic Traits of Polyploid Poplar Hybrids and Clones in Northeast China.

To evaluate differences among 19 different ploidy hybrid poplar clones grown in northeast China, 21 traits related to growth traits and photosynthetic characteristics were detected and analyzed. Abundant phenotypic variations exist among and within populations, and these variations are the basis of forest tree genetic improvements. In this research, variance analysis showed that the traits except the net photosynthesis rate among the different ploidies and all the other traits exhibited significant differences among the ploidies or clones (p < 0.01). Estimation of phenotypic coefficients of variation, genotypic coefficients of variation, and repeatability is important for selecting superior materials. The larger the value, the greater the potential for material selection improvement. The repeatability of the different traits ranged from 0.88 to 0.99. The phenotypic and genotypic coefficients of variation of all the investigated traits ranged from 6.88% to 57.40% and from 4.85% to 42.89%, respectively. Correlation analysis showed that there were significant positive correlations between tree height, diameter, and volume. Transpiration rate, intercellular carbon dioxide concentration, and stomatal conductance were significantly positively correlated with each other but negatively correlated with instantaneous water use efficiency. Growth traits were weakly correlated with photosynthetic indexes. The rank correlation coefficient showed that most of the growth indicators reached a significant correlation level among different years (0.40-0.98), except 1-year-old tree height with 4-year-old tree height and 1-year-old ground diameter with 3-year-old tree height, which indicated the potential possibility for early selection of elite clones. Principal analysis results showed that the contribution rate of the first principal component was 46.606%, and 2-year-old tree height, 2-year-old ground diameter, 3-year-old tree height, 3-year-old ground diameter, 3-year-old diameter at breast height, 3-year-old volume, 4-year-old tree height, 4-year-old ground diameter, 4-year-old diameter at breast height, and 4-year-old volume showed higher vector values than other traits. With the method of multiple-trait comprehensive evaluation to evaluate clones, SX3.1, SY3.1, and XY4.2 were selected as elite clones, and the genetic gains of height, basal diameter, diameter at breast height, and volume of selected clones ranged from 12.85% to 64.87% in the fourth growth year. The results showed fundamental information for selecting superior poplar clones, which might provide new materials for the regeneration and improvement of forests in Northeast China.

Light-Activated Reactive Oxygen Species-Responsive Nanocarriers for Enhanced Photodynamic Immunotherapy of Cancer.

Exploring polymeric nanoplatforms combined with reactive oxygen species (ROS) responsiveness with mitochondria targeting has emerged as an effective strategy for enhanced photodynamic therapy (PDT). Amphiphilic copolymers were synthesized by reacting acrylamide thioketal (TK) linkers with amino-terminated triphenylphosphonium-polyethylene glycol and dodecylamine for encapsulating chlorin e6 (Ce6) via self-assembly. Then, anionic cladding with tumor targeting deshelled in tumor acidic microenvironments was surface-anchored by electrostatic forces (BioPEGDMA@RM). After sequential targeting to the mitochondria of cancerous cells, BioPEGDMA@RM could be light-activated with Ce6 released upon ROS cleavage of TK linkages. It was found that Ce6-loaded BioPEGDMA@RM exhibited higher cytotoxicity on CT26 cells and performed stronger ability on the production of ROS than that without TK linkers. Moreover, a minimum illumination of 3 and 5 min could be required for achieving the maximum release of Ce6 and high in vitro cytotoxicity for Ce6-loaded BioPEGDMA@RM, respectively. Furthermore, Ce6-loaded BioPEGDMA@RM showed 1.29-fold and 1.21-fold higher tumor inhibition on BALB/c nude mice and Kunming mice and stimulated immunologic reactions with more generation of IFN-γ and TNF-α and activation of CD3+, CD4+, and CD8+ T-lymphocytes and DCs than that of Ce6-loaded nanoparticles without TK bonds. This work provided an academic reference for the development of ROS-responsive drug delivery systems for advanced PDT efficiency.

An Outbreak of Coxsackievirus A6 Infection in Adults of a Collective Unit, China, 2019.

Outbreaks/epidemics caused by coxsackievirus A6 (CVA6) have been reported continuously since 2008. However, outbreaks of ocular conjunctival hemorrhage caused by CVA6 in adults in a collective unit have not been reported. Methods. The epidemiological investigations were carried out according to the monitoring program, and the clinical data were collected from the treated hospitals. The nasopharyngeal swab specimens were collected to extract the total nucleic acid (DNA/RNA). The pathogen was determined using nucleic acid detection kits for 22 respiratory pathogens. The VP1 gene of this pathogen was amplified and sequenced. Sequence alignment and analysis were performed using BioEdit 7.0. The gene phylogenetic tree was constructed with MEGA4.0. Results. The factory emerged patients in succession from February 14 and reached the peak on the 18th. A total of 19 workers had symptoms in this factory up to March 31, 2019, giving an attack rate of 8.26%. The main symptoms were rash, ocular conjunctival hemorrhage, fever, and sore throat. The laboratory results showed that coxsackievirus A6 was the main pathogen causing this outbreak. The risk of taking a bath in the bathroom was 7.37 times higher than that of not taking a bath (95% confidence interval (CI): 1.67-32.79). Conclusion. This manuscript further enriched the infection-related information of CVA6, which was helpful to better identify and deal with the epidemic in the future.

Prognostic model of immune-related genes for patients with hepatocellular carcinoma.

Background: Immune-related genes (IRGs) are closely connected to the occurrence and development of tumors. Their influence on the prognosis of patients with HCC, however, remains unclear. Methods: From the TCGA database, we integrated 365 liver cancer tissues and 50 normal tissues to identify differential immune genes related to prognosis. Multivariate COX analysis was used to establish a new prognostic index on account of IRGs, whereby risk score = (Expression level of HSPA4*0.022) + (Expression level of PSMD14*0.042) + (Expression level of RBP2*0.019) + (Expression level of MAPT*0.197) + (Expression level of TRAF3*0.146) + (Expression level of NDRG1*(0.006) + (Expression level of NRAS*0.027) + (Expression level of IL17D*0.075). Results: The risk score was clearly correlated with an unfavorable survival rate and with clinical characteristics. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1-, 3- and 5-year AUC of 0.721, 0.747 and 0.781, respectively). Conclusion: We have established a valuable prognostic risk score for HCC patients that may be a better predictor of survival than the present method. With the risk score's strong predictive value for immune cells and functions, it may provide clinical guidance for the diagnosis and prognosis of different immunophenotypes, and provide multiple therapeutic targets for the treatment of HCC patients based on subtype-specific immune molecules.

The protective effect of MiR-27a on the neonatal hypoxic-ischemic encephalopathy by targeting FOXO1 in rats.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE), a kind of hypoxic-ischemic brain damage caused by perinatal asphyxia, is the most crucial cause of neonatal death and long-term neurological dysfunction in children. We aimed to investigate the protective effects of micro (mi)R-27a on HIE in neonatal rats. Methods: A rat model of neonatal HIE was constructed by modification of the Rice-Vannucci model. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the expressions of miR-27a, FOXO1 messenger RNA (mRNA), interleukin-1ß (IL-1ß) mRNA, and tumor necrosis factor-α (TNF-α) mRNA, and western blot was applied to test the expression of FOXO1. In order to overexpress miR-27a, an intracerebroventricular injection (i.c.v) of miR-27a mimic was administered. We adopted 2,3,5-triphenytetrazolium chloride (TTC) staining and brain water content measurement to test the effects of miR-27a on the infarcted volume and edema in brain after HIE. Flow cytometry (FCM) analysis was applied to test the effects of miR-27a on the infiltrated peripheral immune cells in the rat brains after HIE. Results: We successfully established a rat model of neonatal HIE. It was revealed that the expressions of miR-27a decreased gradually after HIE, however, the expressions of FOXO1 mRNA increased. After injection of the miR-27a mimic, the expression of miR-27a in the rat HIE model brains was significantly upregulated, however, the expression of FOXO1 was robustly downregulated. Both TTC staining and brain water content showed that the infarcted volume and brain edema was markedly increased after HIE. Interestingly, the overexpression of miR-27a reduced the infarcted volume and edema induced by HIE. Additionally, RT-qPCR and FCM analysis showed that HIE lead to increases of IL-1ß, TNF-α, and infiltrated immune cells. Overexpression of miR-27a could reduce the expressions of IL-1ß mRNA and TNF-α mRNA, and the cell numbers of infiltrated peripheral macrophages and neutrophils in the brain. Conclusions: MiR-27a plays protective roles by reducing infarct volume and brain edema, and inhibiting inflammatory factors and infiltrated peripheral immune cells by targeting FOXO1 in neonatal HIE rats.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia.

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.

Clinical application value of serum neutrophil gelatinase-associated lipocalin in neonatal sepsis.

BACKGROUND: To explore the value of serum neutrophil gelatinase-associated lipocalin (sNGAL) in the diagnosis and follow up of neonatal late-onset sepsis. METHODS: A total of 69 infants were enrolled in this prospective study, including 49 infants of late-onset neonatal sepsis in the observation group, and 20 infants without infection serving as the control group. The sNGAL, C-reactive protein (CRP), and procalcitonin (PCT) concentrations were determined in both groups and compared at different time points. A receiver operating characteristic (ROC) curve was drawn to evaluate the values of the 3 parameters in the forecast of neonatal late-onset sepsis. RESULTS: The levels of sNGAL, CRP, and PCT were all increased obviously (P<0.05) in the observation group on the first and second day following onset, compared to the control group. The sNGAL level was associated with the time of treatment. Surprisingly, the sNGAL level started to drop in the observation group with effective treatment on the 7th day following onset. A correlation was found between the concentration of sNGAL and inflammatory markers, such as CRP and PCT, on the first day. The area under the ROC curve (AUC) for sNGAL, CRP, and PCT was: 0.964, 0.925, and 0.94, respectively. CONCLUSIONS: Increased sNGAL levels could reflect the inflammatory status in the acute stage of neonatal sepsis. When combined with other sepsis markers, such as CRP and PCT, the sNGAL is a useful marker in the rapid diagnosis and follow up of neonatal sepsis.

[Effects of Long-term Fertilization on Soil Nutrient Characteristics and Microbial Resource Restrictions in a Terrace on the Loess Plateau].

Long-term fertilization has an important effect on soil fertility and soil microbial activity. In order to explore the effects of long-term fertilization on soil extracellular enzyme activities and nutrient characteristics in a terrace on the Loess Plateau, we based our investigation on the long-term nutrient localization plot of Ansai Soil and Water Conservation Experimental Station, Chinese Academy of Sciences. We measured the soil physicochemical properties, microbial biomass, and extracellular enzyme activities of six fertilization treatments, which included no fertilization (CK); manure and nitrogen fertilization (MN); manure and phosphate fertilization (MP); manure, nitrogen, and phosphate fertilization (MNP); manure (M); and nitrogen and phosphate fertilization (NP). The results showed that all fertilization treatments significantly increased soil nutrient content and soil extracellular enzyme activities compared with that in CK. Correlation analysis showed that extracellular enzyme activity and soil physicochemical properties had an extremely significant correlation. The redundancy analysis indicated that soil nutrient and soil microbial biomass could explain 79.66% and 74.87% of the variation in soil extracellular enzyme activity and its stoichiometric ratio, respectively. Thus, the effects of fertilization on soil fertility were primarily through influencing soil extracellular enzyme activities indirectly. M, MN, MP, and MNP significantly improved soil organic carbon (SOC); soil total nitrogen (STN); and carbon (C), nitrogen (N), and phosphorus (P) source enzyme content; however, MNP changed the soil pH, which had an inhibitory effect on microbial activities. Vector analysis showed that the microbial communities of all treatments were in the condition of P limitation. Although MNP could alleviate the extent of P limitation, there was no significant difference between M and MP. Our study indicated that long-term application of manure[7500 kg·(hm2·a)-1]could meet the nutrient requirements of dryland crop growth, and long-term application of manure combined with phosphorus fertilization could alleviate the resource constraints faced by microorganisms. Consequently, our results provide a new insight into improving regional nitrogen excess.

PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF.

OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats.

Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis-based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune-related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune-related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them THBS1, IL-10, and NR4A3 expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.

Analysis of malaria cases re-examination results of malaria diagnostic reference laboratory in Nantong, Jiangsu / 中国热带医学

@#Abstract: Objective　To analyze the laboratory microscopic re-examination results of malaria cases in Nantong of the National Notifiable Disease Report System from 2014 to 2021 by Nantong Malaria Diagnostic Reference Laboratory, so as to evaluate the malaria diagnosis ability of Nantong Malaria Diagnostic Reference Laboratory. Methods　The blood smear and blood samples of malaria cases in Nantong from 2014 to 2021 of the National Notifiable Disease Report System were collected. Nantong Malaria Diagnostic Reference Laboratory and Jiangsu Institute of Parasitic Diseases carried out the re-examination of municipal and provincial laboratories, taking the results of provincial laboratory as the standard to compare and analyze the re-examination results of Nantong Malaria Diagnostic Reference Laboratory. Results　From 2014 to 2021, the two-level laboratories in Nantong city and Jiangsu Province re-examined the blood samples of 297 malaria cases. The microscopic examination and PCR re-examination results at the provincial level were the same：292 positive cases and 5 negative cases. The qualitative coincidence rate between Nantong microscopic re-examination results and the provincial re-examination results was 100% (297/297), without misjudgment and omission. The coincidence rate of Plasmodium typing was 96.23% (281/292). The coincidence rate of P. falciparum, P. vivax, P. ovale and P. malaria were 99.57% (234/235), 62.50% (5/8), 89.47% (34/38) and 72.73% (8/11) respectively. The consistency test results showed that the Kappa value of Plasmodium typing results between municipal and provincial laboratories was 0.89. The Kappa values of P. falciparum, P. vivax， P. ovale and P. malaria were 0.98, 0.58, 0.87 and 0.79 respectively. Conclusion　The malaria diagnosis ability of Nantong Malaria Diagnostic Reference Laboratory is generally good, and it is necessary to improve the ability of Plasmodium typing.