Fluorescent hyaluronic acid nanoprodrug: A tumor-activated autophagy inhibitor for synergistic cancer therapy.

Autophagy is a process that eliminates damaged cells and malfunctioning organelles via lysosomes, which is closely linked to cancer. Primaquine (PQ) was reported to impede autophagy flow by preventing autophagosomes from fusing with lysosomes at the late stage of autophagy. It will lead to cellular metabolic collapse and programmed cell death. Excessive or extended autophagy enhances the efficacy of chemotherapeutic drugs in cancer prevention. The utilization of autophagy inhibition in conjunction with chemotherapy has become a prevalent and reliable approach for the safe and efficient treatment of cancer. In this work, an acid-sensitive nanoprodrug (O@PD) targeting CD44 receptors was produced using Schiff-base linkages or electrostatic interactions from oxidized hyaluronic acid (OHA), PQ, and doxorubicin (DOX). The CD44-targeting prodrug system in triple-negative breast cancer (TNBC) cells was designed to selectively release DOX and PQ into the acidic tumor microenvironment and cellular endosomes. DOX was employed to investigate the cellular uptake and ex-vivo drug distribution of O@PD nanoprodrugs. PQ-induced autophagy suppression combined with DOX has a synergistic fatal impact in TNBC. O@PD nanoprodrugs demonstrated robust anticancer efficacy as well as excellent biological safety, making them suitable for clinical use.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Modulating the electronic properties and band alignments of the arsenene/MoSi2N4 van der Waals heterostructure via applying strain and electric field.

The two-dimensional (2D) MoSi2N4 monolayer fabricated recently has attracted extensive attention due to its exotic electronic properties and excellent stability for future applications. Using first-principles calculations, we have shown that the electronic properties of the arsenene/MoSi2N4 van der Waals (vdW) heterostructure can be effectively modulated by applying in-plane/vertical strain and vertical electric field. The arsenene/MoSi2N4 vdW heterostructure has type-II band alignment, facilitating the separation of photogenerated electron-hole pairs. The heterostructure is predicted to have an indirect bandgap of about 0.52 eV by using the PBE functional (0.87 eV by using the hybrid functional). Furthermore, under εz = 0.5 Å vertical tensile strain or -0.05 V Å-1 vertical electric field, the arsenene/MoSi2N4 heterostructure can not only experience transition from an indirect to a direct bandgap semiconductor, but also exhibit type-II to type-I band alignment transition. The calculated optical absorption properties reveal that the formation of the vdW heterostructure can effectively enhance the light absorption, and the absorption coefficient in visible and ultraviolet regions is much higher than those of the arsenene and the MoSi2N4 monolayer. Most importantly, based on charge transfer analysis, we proposed the modulation mechanism of the electronic properties of the vdW heterostructure influenced by vertical strain and electric field. Our study provides physical insights into manipulating the electronic and optoelectronic properties of MoSi2N4 based vdW heterostructures, which may be helpful for their practical applications.

First principles study of BAs/MoSi2N4 van der Waals heterostructure: tunable electronic and optical properties via vertical strain.

Constructing van der Waals heterostructures from layered materials can form new optoelectronic devices with superior performance to the individual monolayers. Here, we use first-principles calculations to explore the modulation of a two-dimensional BAs/MoSi2N4 van der Waals heterostructure via strain, including the structure stabilities, electronic properties, charge transfer, and optical properties. Our calculated results reveal that the BAs/MoSi2N4 heterostructure has a direct bandgap of 0.72 eV and type-I band alignment. In addition, the BAs/MoSi2N4 heterostructure exhibits enhanced light absorption in the visible light region. The electronic properties of the BAs/MoSi2N4 heterostructure are tunable by vertical strain, exhibiting a direct to indirect bandgap transition as well as a type-I to type-II band alignment transition when the vertical distance is reduced. Our research provides a comprehensive understanding of the electronic and optical properties of the BAs/MoSi2N4 heterostructure and could be helpful for their potential applications in optoelectronic devices.

Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis.

PURPOSE: To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. RESULTS: After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2-3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0-1 CNN. For patients with grade 0-1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). CONCLUSION: Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0-1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.

A rare case of severe leptospirosis infection presenting as septic shock in a non-endemic area: a case report and literature review.

BACKGROUND: Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist. CASE PRESENTATION: A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days. CONCLUSION: We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection.

Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers.

BACKGROUND: The diagnostic and economic value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale. AIM: To reassess the diagnostic and economic value of the three tumor biomarkers. METHODS: A retrospective analysis of all 32857 subjects who underwent CEA, CA19-9, CA72-4, gastroscopy and colonoscopy from October 2006 to May 2018 was conducted. Then, we assessed the discrimination and clinical usefulness. Total cost, cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes (gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive). RESULTS: The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer (CRC), while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers (GICs). Regarding early diagnosis, only CEA could be used for early CRC. The combination of biomarkers didn't greatly increase the area under the curve. The economic indicators of CEA were superior to those of CA19-9, CA72-4 and any combination. At the threshold of 1.8 µg/L to 10.4 µg/L, all four indicators of CEA were lower than those in the scheme that conducted gas-trointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable. CONCLUSION: CEA had qualified diagnostic value for CRC and superior economic value for GICs, especially for elderly health checkup subjects. CA72-4 was not suitable as a diagnostic biomarker.

Long-term outcomes of chemoradiotherapy versus radiotherapy alone in patients with intermediate-risk nasopharyngeal carcinoma: a population-based analysis.

PURPOSE: To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT). METHODS: We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004-2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates. RESULTS: A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45-0.71) and CSS (HR 0.55, 95% CI 0.39-0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39-0.92) and CSS (HR 0.60, 95% CI 0.40-0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38-0.70) and T3N0 (HR 0.64, 95% CI 0.42-0.98) rather than T2N0 (HR 1.00, 95% CI 0.51-1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24-0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56-5.97) and T3N0 (HR 0.56, 95% CI 0.28-1.12). CONCLUSION: For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results.

First-principles study of O-functionalized two-dimensional AsP monolayers: electronic structure, mechanical, piezoelectric, and optical properties.

Using density functional theory, we investigated the geometrical properties, electronic structures, carrier mobilities, piezoelectric coefficients, and optical absorption behaviors of three O-functionalizedß-phase AsP structures (b-AsPO-FO, b-AsPO-As-SO and b-AsPO-P-SO). It is shown that three O-functionalized monolayers are all indirect semiconductors with bandgaps of 0.21, 0.67, and 0.80 eV, respectively. Our calculations demonstrated that the pristine AsP monolayer and these O-functionalized AsP monolayers have strongly anisotropic carrier mobilities, allowing their potential applications for in-plane anisotropic electronic device. The bandgaps of three functionalized nanomaterials exhibit non-monotonic variations under the biaxial strains changing from -0.10 to +0.10, all experiencing metal-indirect bandgap-direct bandgap transition. The calculated in-plane Young's modulus results suggest that they are fairly flexible to allow the application of large elastic strains on the chemically functionalized AsP monolayers. Furthermore, the b-AsPO-FO monolayer exhibits excellent anisotropic light-harvesting behavior (absorption peak: 2.36 and 2.76 eV alongxand 2.37 eV alongydirection) in visible light region. The b-AsPO-As-SO and b-AsPO-P-SO monolayers have strong absorption peak at 2.60 eV and 2.87 eV, respectively. The tunable electronic structures, anisotropic carrier mobility, and excellent optical absorption properties may facilitate practical applications of O-functionalized b-AsP monolayers in nanoelectronics and photovoltaics.

[Kirschner wire retractor-assisted reduction and inverted insertion of elastic nail in the treatment of children's irreducible subradial 1/3 fractures].

OBJECTIVE: To explore the clinical effect of Kirschner wire retractor-assisted reduction and inverted insertion of elastic nail in the treatment of children's irreducible subradial 1/3 fractures. METHODS: A total of 34 children with irreducible subradial 1/3 fractures treated by surgery from August 2016 to December 2020 were retrospective analyzed. Among them, 16 cases underwent Kirschner wire retractor-assisted closed reduction and percutaneous elastic intramedullary nailing with inverted insertion(observation group), 10 males and 6 females, aged from 4 to 10 years old with an average of(6.0±0.4)years;18 cases underwent open reduction and plate internal fixation (control group), 11 males and 7 females, the age from 3 to 10 years with an average of(7.0±0.5) years. The operation time, intraoperative blood loss, hospital stay, incision length, fracture healing time and complications of the two groups were observed and the wrist function was evaluated by Cooney wrist joint score. RESULTS: All patients were followed up for 3-12 years old with an average of (11.40±0.48) months in the observation group and 4-13 months with an average of (11.50±0.39) months in the control group. Bone healing was achieved in all patients, and there was no incision infection in both groups. The operation time, intraoperative blood loss, hospital stay and incision length in observation groups were lower than those of control group (P<0.05). There was no significant difference in the fracture healing time between two groups(P>0.05). There was no significant difference in postoperative healing and recovery of wrist function between groups(P>0.05). CONCLUSION: Compared with open reduction and plate internal fixation, Kirschner wire retractor-assisted reduction and percutaneous elastic intramedullary nail fixation for irreducible subradial radial 1/3 fractures has the advantages of less trauma, shorter operation time, less blood loss, and satisfactory short-term clinical results.

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma.

Purpose: The role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT). Methods: We searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3-4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy. Results: Nine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44-0.82), LRFS (HR = 0.62, 95% CI 0.50-0.78), and PFS (HR = 0.65, 95% CI 0.54-0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46-1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62-1.15), LRFS (HR = 0.85, 95% CI 0.54-1.34), DMFS (HR = 0.96, 95% CI 0.60-1.54), and PFS (HR = 0.96, 95% CI 0.66-1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37-2.96), LRFS (HR = 0.70, 95% CI 0.34-1.45), DMFS (HR = 1.03, 95% CI 0.53-2.00), and PFS (HR = 1.04, 95% CI 0.58-1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3-4 leukopenia (RR = 4.00, 95% CI 2.29-6.97), mucositis (RR = 1.43, 95% CI 1.16-1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63-29.12). No significant differences of grade 3-4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85-13.94) was found between the two groups. Conclusion: For unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

Saikosaponin D Inhibited IL-1ß Induced ATDC 5 Chondrocytes Apoptosis In Vitro and Delayed Articular Cartilage Degeneration in OA Model Mice In Vivo.

Osteoarthritis (OA) is the most common joint disease in the elderly, characterized by cartilage degradation and proliferation of subchondral bone. The pathogenesis of OA involves a variety of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß. From the molecular mechanism, the nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway and the expression of ROS regulated the production of the above inflammatory mediators. Saikosaponin D (SSD), which is an active ingredient isolated from Bupleurum, has various biological functions. In this study, IL-1ß was used as a pro-inflammatory factor to create an in vitro OA model. According to the results of high-density culture, qPCR, ROS measurement, Western blot, and immunofluorescence, SSD activated the Nrf2/HO-1/ROS axis, inhibited the production of inflammatory mediators, and protected against ECM destruction. The DMM mouse model was used as a model of OA in mice. From the results of safranin O/fast green staining, hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and OARSI scores, SSD protected against the mice knee articular cartilage degeneration and reduced the number of osteoclasts in the subchondral bone. Experimental results found that SSD suppressed IL-1ß-induced differentiated ATDC 5 chondrocytes apoptosis via the Nrf2/HO-1/ROS axis in vitro. SSD delayed the progression of OA in DMMs model mice in vivo. Therefore, SSD has the potential to become a drug for clinical treatment of OA.

Effects of Air Pollutant Exposure on Exacerbation Severity in Asthma Patients with or without Reversible Airflow Obstruction.

BACKGROUND: Reversible airflow obstruction (RO) and fixed airflow obstruction (FO) are two important clinical phenotypes of asthma. However, the relationship between air pollutant exposure and exacerbation of the two phenotypes is unknown. OBJECTIVE: To study the effects of air pollutant exposure on exacerbation severity in asthma patients with or without FO. METHODS: A total of 197 severe asthma patients were enrolled, and divided into two groups: the FO group (n=81) and the RO group (n=116). We collected the demographic data, laboratory parameters, pulmonary function test parameters, and the daily average concentrations of different air particles in Shenzhen on the different lag days of each subject. The receiver operating characteristic (ROC) curve was used to identify the effects of major air pollutants on the severity of asthma patients with RO. RESULTS: Compared with the RO group, the FO group had fewer women, lower body mass index (BMI), longer disease duration, higher smoking history rate, allergic family history rate, FeNO level, and lower levels of large airway parameters. The median exposure levels of PM10 and PM2.5 in the severe RO subgroup were both higher than those in the mild-to-moderate RO subgroup on Lag0, 1 and 3, and the median exposure level of PM1 on Lag0 in the severe RO subgroup was significantly higher than that in the mild-to-moderate RO subgroup. Logistic regression modeling indicated exposure to PM2.5 and PM1.0 on Lag0, and PM10 on Lag0-2 were the independent risk factors for hospital admissions for asthma patients with RO. By performing an ROC curve analysis, PM2.5 on Lag0 (AUC = 0.645, p = 0.027) provided a best performance to predict severe asthma exacerbations with RO, with a sensitivity of 36.0% and a specificity of 91.2%. CONCLUSION: Short-term exposure to PM10, PM2.5 and PM1 may play a role in exacerbation severity among asthma patients with RO.

Increased levels of serum IL-17 and induced sputum neutrophil percentage are associated with severe early-onset asthma in adults.

BACKGROUND: Differences between adult patients with severe early-onset and late-onset asthma have not been well studied. OBJECTIVES: To determine the phenotypic distinction regarding age at onset in patients with severe asthma. METHODS: The present study enrolled thirty-two patients with severe early-onset (onset age < 12 years) asthma and thirty-two patients with severe late-onset (onset age > 12 years) asthma. Severe asthma was defined according to Global Initiative for Asthma criteria. The clinical, spirometric, and laboratory parameters were collected for group comparisons. RESULTS: Among the 64 patients included (mean age, 46.22 ± 13.90 years; 53.1% male), the mean percent of predicted forced expiratory volume in 1 s (FEV1) was 68.43 ± 20.55%. Patients with severe early-onset asthma had a younger age, longer duration of asthma, higher rate of family history, and better small-airway function (MEF25% and MMEF75/25%) compared with severe late-onset asthma. Furthermore, levels of serum IL-17 and sputum neutrophil percentage were significantly higher for patients with severe early-onset asthma (P = 0.016, 0.033, respectively). Multiple logistic regression analysis revealed that increased serum IL-17 (odds ratio = 1.065, P = 0.016) was independently associated with severe early-onset asthma. The combination of serum IL-17 and sputum neutrophil percentage yielded a sensitivity of 80.0% and a specificity of 86.7% for identifying patients with severe early-onset asthma. CONCLUSIONS: Patients with severe early-onset asthma exhibit elevated levels of serum IL-17 and sputum neutrophil percentage, suggesting a potential role in the pathogenesis of severe early-onset phenotype.

Optimized combination of circulating biomarkers as predictors of prognosis in AECOPD patients complicated with Heart Failure.

Background: Systematic inflammation, nutritional status, and cardiovascular function have been associated with the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with heart failure (HF). However, the value of their relevant biomarkers in predicting mortality has not been well defined yet. We aimed to investigate the prognostic value of circulating biomarkers including C-reaction protein (CRP)/albumin (ALB), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and N-terminal pro-brain natriuretic peptide (NT-proBNP) for AECOPD patients with HF. Methods: A retrospective study was carried out in the Second Clinical College of Jinan University from January 1, 2013 to January 31, 2019. A total of 146 cases of AECOPD complicated with HF were enrolled and classified into survivor group (n=94) and non-survivor group (n=52). The baseline characteristics, CRP/ALB ratio, NLR, PLR, serum levels of NT-proBNP, and other indicators were collected. The predictors for prognosis were analyzed by multivariate logistic regression, and the ability to predict 28-day mortality was evaluated by receiver operating characteristics curve (ROC) and the area under the curve (AUC). Results: The patients in non-survivors had significantly higher levels of CRP, CRP/ALB, NLR, PCT and NT-proBNP, but lower ALB levels compared to the survivors [111.7 (56.9, 186.5) VS. 43.8 (10.3, 96.1) mg/L, 4.6 (2.0, 8.0) VS. 1.4 (0.3, 3.4), 22.2 (11.1, 40.1) VS. 12.0 (6.2, 24.8), 2.6 (0.2, 10.3) VS. 0.08 (0.1, 0.5) ng/ml, 17912.5 (9344.0, 34344.5) VS. 9809.0 (4415.9, 16387.2) ng/ml, 25.8 (23.2, 30.5) VS. 30.7 (27.9, 34.1) g/L; P < 0.001, <0.001, 0.001, <0.001, <0.001, and < 0.001, respectively]. No significant difference in PLR was found between the two groups (P=0.413). The logistic analysis revealed that CRP/ALB (OR=1.303, 95%CI: 1.145-1.483, P<0.001), NT-proBNP (OR=1.041, 95%CI: 1.010-1.073, P=0.009) and NLR (OR=1.010, 95%CI: 0.999-1.022, P<0.001) are independent risk factors for predicting the 28-day mortality. The AUC of the ROC curves were 0.768, 0.767, 0.757, 0.723, 0.716, and 0.668 for CRP/ALB, PCT, CRP, NT-proBNP, ALB, and NLR, respectively. The combination of CRP/ALB, NLR and NT-proBNP as biomarkers was shown to have better accuracy for predicting prognosis (AUC=0.830, 95%CI: 0.761-0.899, P<0.001), with a higher specificity of 80.8% and specificity of 77.7% as compared with each single biomarkers. Conclusions: High levels of NLR, CRP/ALB and NT-proBNP may be clinical usefully predictors for death in AECOPD patients with HF. Combination of NLR with CRP/ALB and NT-proBNP can provide a higher accuracy for predicting 28-day mortality in these patients.

Combining Blood-Based Biomarkers to Predict Mortality of Sepsis at Arrival at the Emergency Department.

BACKGROUND Our aim was to determine a useful combination of blood biomarkers that can predict 28-day mortality of sepsis upon arrival at the Emergency Department (ED). MATERIAL AND METHODS Based on Sepsis-3.0, 90 sepsis patients were enrolled and divided into survivor and nonsurvivor groups with day 28 as the study end point. After comparing the demographic data and clinical characteristics of patients, we evaluated the predictive validity of a combination of markers including interleukin-6 (IL-6), procalcitonin (PCT), and lactate at arrival at the ED. Independent risk factors were found by using univariate and multivariate logistic regression analyses, and the prognostic value of markers was determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS There were 67 (74.4%) survivors and 23 (25.6%) nonsurvivors. The levels of IL-6 (survivors vs nonsurvivors: median 205.30 vs 3499.00 pg/mL, P=0.012) and lactate (survivors vs. nonsurvivors: median 2.37 vs 5.77 mmol/L, P=0.003) were significantly lower in survivor group compared with the nonsurvivor group. Markers including IL-6, PCT, lactate, and neutrophil-to-white blood cell ratio (NWR) were independent risk factors in predicting 28-day mortality due to sepsis. The combination of these 4 markers provided the best predictive performance for 28-day mortality of patients with sepsis, on arrival at the ED (AUC of 0.823, 95% confidence interval [CI] 0.723-0.924), and its accuracy, specificity, and sensitivity were 74.4% (95% CI 64.0-82.8%), 91% (95% CI 80.9-96.3%), and 65% (95% CI 42.8-82.8%), respectively. CONCLUSIONS The combination of IL-6, PCT, lactate, and NWR measurements is a potential predictor of 28-day mortality for patients with sepsis, at arrival at the ED. Further research is needed to confirm our findings.

Mortality prediction using a novel combination of biomarkers in the first day of sepsis in intensive care units.

Early identification of infection severity and organ dysfunction is crucial in improving outcomes of patients with sepsis. We aimed to develop a new combination of blood-based biomarkers that can early predict 28-day mortality in patients with sepsis or septic shock. We enrolled 66 patients with sepsis or septic shock and compared 14 blood-based biomarkers in the first 24 h after ICU admission. The serum levels of interleukin-6 (IL-6) (median 217.6 vs. 4809.0 pg/ml, P = 0.001), lactate (median 2.4 vs. 6.3 mmol/L, P = 0.014), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (median 1596.5 vs. 32,905.3 ng/ml, P < 0.001), prothrombin time (PT) (median 15.6 vs. 20.1 s, P = 0.030), activated partial thrombin time (APTT) (median 45.1 vs. 59.0 s, P = 0.026), and international normalized ratio (INR) (median 1.3 vs. 1.8, P < 0.001) were significantly lower in the survivor group. IL-6, NT-proBNP, and INR provided the best individual performance in predicting 28-day mortality of patients with sepsis or septic shock. Furthermore, the combination of these three biomarkers achieved better predictive performance (AUC 0.890, P < 0.001) than conventional scoring systems. In summary, the combination of IL-6, NT-proBNP, and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock.

Expression of herpesvirus entry mediator gene as a potential biomarker for disease severity in patients with persistent asthma.

Objectives: Herpes virus entry mediator (HVEM) is a costimulatory molecule, and has been proved to play an important role in airway inflammatory and remodeling processes of asthma. We aimed to investigate the expression of HVEM gene in patients with asthma as a means of assessing disease severity.Methods: This study was carried out on 59 subjects, 16 patients with mild persistent asthma, 11 patients with moderate persistent asthma, 13 patients with severe persistent asthma, and 19 age and gender matched healthy controls. The HVEM mRNA expressions of all subjects were determined by real time PCR. Correlations between HVEM mRNA expression and fractional exhaled nitric oxide (FeNO), pulmonary function test values, total blood white cell count and differential, total immunoglobulin E (IgE) level, and Asthma Control Test (ACT) score were analyzed, respectively. The discrimination abilities of HVEM mRNA between different groups were tested using receiver operating characteristics (ROC) curve analyses.Results: This study showed the expressions of HVEM mRNA were significantly higher in the patients with severe and moderate persistent asthma than in patients with mild persistent asthma and healthy subjects (2.97 ± 1.23 vs. 1.17 ± 0.42 vs. 0.62 ± 0.38 vs. 0.46 ± 0.18/NAPDH, p < 0.001), but there was no significant difference between patients with mild persistent asthma and health controls (0.62 ± 0.38 vs. 0.46 ± 0.18/NAPDH, p = 0.557). HVEM mRNA expression at cut off point [1.01/NAPDH, area under the ROC curve (AUC) = 0.99] is sufficient to discriminate severe patients from mild-to-moderate patients, and at cut off point (0.93/NAPDH, AUC = 0.91) for discrimination of moderate-to-severe patients from mild ones, while at cut off point (0.76/NAPDH, AUC = 0.75) for discrimination of asthmatic patients from controls. Furthermore, HVEM mRNA expression was positively correlated with FeNO level (r = 0.524, p = 0.015), and total lymphocyte count (r = 0.426, p = 0.017) in patients with persistent asthma.Conclusions: HVEM gene expressions can be used as a potential biomarker for evaluating the severity of patients with persistent asthma.

Information Flow Analysis between EPU and Other Financial Time Series.

We investigate the strength and direction of information flow among economic policy uncertainty (EPU), US imports and exports to China, and the CNY/US exchange rate by using the novel concept of effective transfer entropy (ETE) with a sliding window methodology. We verify that this new method can capture dynamic orders effectively by validating them with the linear transfer entropy (TE) and Granger causality methods. Analysis shows that since 2016, US economic policy has contributed substantially to China-US bilateral trade and that China is making passive adjustments based on this trade volume. Unlike trade market conditions, China's economic policy has significantly influenced the exchange rate fluctuation since 2016, which has, in turn, affected US economic policy.