Computational design and preparation of water-compatible noncovalent imprinted microspheres.

Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres. The proposed approach involved computational modelling for screening functional monomers and a simple method for preparing monodisperse and highly cross-linked microspheres. The fabricated non-imprinted polymer (NIP) and 2,4-d-imprinted polymer (2,4-d-MIP) were characterised, and their adsorption capabilities in an aqueous environment were evaluated. Results reveal that the pseudo-second-order kinetics model was appropriate for representing the adsorption of 2,4-D on NIP and 2,4-d-MIP, with R2 values of 0.97 and 0.99, respectively. The amount of 2,4-D adsorbed on 2,4-d-MIP (97.75 mg g-1) was considerably higher than those of phenoxyacetic acid (35.77 mg g-1), chlorogenic acid (9.72 mg g-1), spiramycin (1.56 mg g-1) and tylosin (1.67 mg g-1). Furthermore, it exhibited strong resistance to protein adsorption in an aqueous medium. These findings confirmed the feasibility of the proposed approach, providing a reference for the development of water-compatible noncovalent imprinted polymers.

Unveiling the link between inflammasomes and skin cutaneous melanoma: Insights into expression patterns and immunotherapy response prediction.

Skin cutaneous melanoma (SKCM) is one of the most malignant forms of skin cancer, characterized by its high metastatic potential and low cure rate in advanced stages. Despite advancements in clinical therapies, the overall cure rate for SKCM remains low due to its resistance to conventional treatments. Inflammation is associated with the activation and regulation of inflammatory responses and plays a crucial role in the immune system. It has been implicated in various physiological and pathological processes, including cancer. However, the mechanisms of inflammasome activation in SKCM remain largely unexplored. In this study, we quantified the expression level of six inflammasome-related gene sets using transcriptomic data from SKCM patients. As a result, we found that inflammasome features were closely associated with various clinical characteristics and served as a favorable prognostic factor for patients. A functional enrichment analysis revealed the oncogenic role of inflammasome features in SKCM. Unsupervised clustering was applied to identify immune clusters and inflammatory subtypes, revealing a significant overlap between immune cluster 4 and SKCM subtype 2. The CASP1, GSDMD, NLRP3, IL1B, and IL18 features could predict immune checkpoint blockade therapy response in various SKCM cohorts. In conclusion, our study highlighted the significant association between the inflammasome and cancer treatment. Understanding the role of inflammasome signaling in SKCM pathology can help identify potential therapeutic targets and improve patient prognosis.

Clinical Value of the Combination Detection of Captopril Renal Scintigraphy and Plasma Renin Activity in the Diagnosis of Renal Hypertension.

OBJECTIVE: This study aimed to investigate the clinical value of the combination detection of captopril renal scintigraphy (CRS) and plasma renin activity (PRA) in the diagnosis of renal hypertension (RHR). METHODS: Retrospective analysis was conducted on the clinical data of 163 patients with suspected RHR admitted to our hospital from March 2019 to March 2021, and all patients underwent blood pressure, CRS and digital subtraction angiography (DSA). The patients were divided into the positive group (n = 100) and the negative group (n = 63) in accordance with the results of DSA examination. PRA, angiotensin II and aldosterone levels of the two groups were detected and compared. The receiver operating characteristic curve was used to analyse the CRS, PRA and combined diagnostic performance. RESULTS: The uptake ratio value after captopril intervention in the positive group was 36.71% ± 8.79%, which was significantly lower than that in the negative group (56.79% ± 10.09%, p < 0.05). The serum PRA level of the positive group was 4.70 ± 1.67 ng/mLꞏh, which was distinctly higher than that of the negative group (2.12 ± 1.03 ng/mLꞏh, p < 0.05). The sensitivity and Youden index under the combination detection (area under the curve (AUC) = 0.956, p < 0.001) were all higher than those under single detection. CONCLUSION: The combined detection of PRA and CRS can provide considerable evidence for the early diagnosis and treatment of RHR, which has a certain clinical value.

Application of Quantitative Parameters of Computed Tomography Texture Combined with the Detection of Serum Manganese Superoxide Dismutase in the Diagnosis of Adrenocortical Adenoma.

OBJECTIVE: This study aimed to explore the application of quantitative parameters of computed tomography (CT) texture combined with the detection of serum manganese superoxide dismutase (MnSOD) in the diagnosis of adrenocortical adenoma (ACA). METHODS: The study selected 147 patients with suspected ACA received in Yantaishan Hospital from November 2019 to November 2021 as the research objects. These patients were divided into the study group (SG, n = 71, ACA) and the reference group (RG, n = 76, non-ACA) according to the postoperative pathological results to implement CT examination and subsequent serological examination. The quantitative parameters of CT texture and serum MnSOD levels were compared between the two groups, and the receiver operating characteristic curve was used to evaluate the value of single and combined diagnosis of quantitative parameters of CT texture and detection of serum MnSOD. RESULTS: Compared with the RG, the SG had notably lower CT values in the plain scan, venous and delayed phase (p < 0.001) and had overtly higher entropy (p < 0.001). However, no remarkable difference was observed in terms of kurtosis and skewness between the two groups (p > 0.05). The serum MnSOD levels of the SG and RG were 27.26 (24.56, 30.97) U/mL and 43.45 (41.02, 45.08) U/mL, respectively, and the MnSOD level of the SG was significantly lower than that of the RG (p < 0.001). The combined diagnosis of CT entropy parameter and MnSOD detection had higher area under the curve (0.91), sensitivity (88.70%) and specificity (82.90%) than those of each single diagnosis (p < 0.001) and had higher diagnostic efficiency. CONCLUSIONS: The entropy in the quantitative parameters of CT texture and detection of MnSOD can be used for the diagnosis of ACA, and their combined diagnosis effect is good, thus providing a new direction for the clinical identification of the disease.

Identification of distinct gene co-expression modules and specific hub genes in skin lesions of atopic dermatitis and psoriasis by WGCNA.

Atopic dermatitis (AD) and psoriasis are among the most common chronic inflammatory skin diseases. Although AD and psoriasis are distinguished using clinical criteria, the lesions of these two diseases are sometimes highly similar, making diagnosis difficult. In addition, the mechanisms underlying these two diseases are not fully clear. Here, we aimed to identify potential genes and regulatory mechanisms in AD and psoriasis patients to aid in the diagnosis and treatment of AD and psoriasis. The GSE121212 dataset was obtained from the NCBI Gene Expression Omnibus database and weighted gene co-expression network analysis (WGCNA) was applied. The functions of genes in modules of interest were determined using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis with the ggplot2 package of r. The hub genes were obtained using the Search Tool for the Retrieval of Interacting Genes database and then visualized using cytoscape. The MEgreen and MEbrown modules were identified to associate with AD and psoriasis, respectively, and the biological functions and pathways of genes in clinically significant modules were detected and analyzed. Hub genes in these two modules and details on potential protein interactions were also revealed. The genes and modules identified by WGCNA might contribute to our understanding of the molecular mechanisms of AD and psoriasis and aid in their diagnosis and treatment.

Hsa-let-7c-5p, hsa-miR-130b-3p, and hsa-miR-142-3p as Novel miRNA Biomarkers for Melanoma Progression.

This study aimed to screen miRNA biomarkers for melanoma progression. Raw melanoma data were downloaded from the Gene Expression Omnibus (GSE34460, GSE35579, GSE18509, and GSE24996) and the Cancer Genome Atlas (TCGA). Then, all differentially expressed miRNAs (DEmiRNAs) between benign vs. primary, metastatic vs. benign, and metastatic vs. primary groups were obtained in the GSE34460 and GSE35579 datasets, and the miRNAs related to disease progression were further screened. Then, the miRNA-gene network was constructed, followed by enrichment, survival, and cluster analyses. Differentially expressed genes (DEGs), tumor-infiltrating immune cells, and tumor mutation burden (TMB) between subtypes were analyzed. miRNAs were verified in the GSE18509 and GSE24996 datasets. A total of 132 and 209 DEmiRNAs were obtained in the GSE34460 and GSE35579 datasets, respectively, and 27 DEmiRNAs related to disease progression were screened. hsa-miR-106b-5p, hsa-miR-27b-3p, and hsa-miR-141-3p had a higher degree and were regulated by numerous genes in the miRNA-gene network. Moreover, four miRNAs were associated with prognosis: hsa-let-7c-5p, hsa-miR-130b-3p, hsa-miR-142-3p, and hsa-miR-509-3p. Furthermore, the bidirectional hierarchical clustering of 27 miRNAs was classified into three subtypes, and TMB and four types of immune cells, including activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells, showed significant differences among the three subtypes. The expression levels of most miRNAs in the GSE18509 and GSE24996 datasets were consistent with those in the training dataset. These miRNAs, including hsa-let-7c-5p, hsa-miR-130b-3p, and hsa-miR-142-3p, and activated dendritic cells, naïve CD4 T cells, M1 macrophages, and plasma cells may play vital roles in the pathogenesis of melanoma.

Metagenomics next-generation sequencing provides insights into the causative pathogens from critically ill patients with pneumonia and improves treatment strategies.

Background: The metagenomics next-generation sequencing (mNGS) is a promising technique for pathogens diagnosis. However, whether the application of mNGS in critically ill patients with pneumonia could cause anti-infection treatment adjustment and thereby affect the prognosis of these patients has not been explored. Methods: We retrospectively collected the clinical data of patients diagnosed with pulmonary infection in the ICU of the Affiliated Hospital of Qingdao University from January 2018 to January 2021. These patients with pneumonia were divided into mNGS group and no-mNGS group by whether being performed NGS or not. The clinical data, including demographics, illness history, APACHE II score, length of mechanical ventilation, length of stay in the hospital, length of stay in ICU and outcome, were collected. In addition, the data of pathogens and anti-infection treatment before and after NGS were also collected. Propensity score matching was performed to evaluate the mortality and deterioration rate between NGS group and non-NGS group. Results: A total of 641 patients diagnosed with pneumonia were screened, and 94 patients were excluded based on exclusion criteria. Finally, 547 patients were enrolled, including 160 patients being performed NGS. Among these 160 patients, 142 cases had NGS-positive results. In addition, new pathogens were detected in 132 specimens by NGS, which included 82 cases with virus, 18 cases with fungus, 17 cases with bacteria, 14 cases with mycoplasma, and 1 case with mycobacterium tuberculosis. Anti-infection treatments were adjusted in some patients who performed NGS, including 48 anti-bacterial treatments, 20 antifungal treatments and 20 antiviral treatments. There were no significant differences in the mortality and deterioration rate between NGS and non-NGS group, but it exhibited a trend that the mortality and deterioration rate of NGS group was lower than non-NGS group after the propensity score matching analysis (15.8% vs 24.3%, P=0.173; 25.6% vs 37.8%, P=0.093). Conclusion: NGS could affect the anti-infection treatments and had a trend of reducing the mortality and deterioration rate of critically ill patients with pneumonia.

Dynamics of Acquired Resistance to Nivolumab Therapies Varies From Administration Strategies.

PURPOSE: The identification of optimal drug administration schedules to overcome the emergence of resistance that causes treatment failure is a major challenge in cancer research. We report the outcomes of a computational strategy to assess the dynamics of tumor progression as a function of time under different treatment regimens. METHODS: We developed an evolutionary game theory model that combined Lotka-Volterra equations and pharmacokinetic properties with 2 competing cancer species: nivolumab-response cells and Janus kinase (JAK1/2) mutation cells. We selected 3 therapeutic schemes that have been tested in the clinical trials: 3 mg/kg Q2w, 10 mg/kg Q2w, and 480 mg Q4w. The simulation was performed under the intervals of 75, 125, and 175 days, respectively, for each regimen. The data sources of the pharmacokinetic parameters used in this study were collected from previous published clinical trials. Other parameters in the evolutionary model come from the existing references. FINDINGS: Predictions under various dose schedules indicated a strong selection for nivolumab-independent cells. Under the 3 mg/kg dose strategy, the reproduction rate of JAK mutation cells was highest, with strongest tumor elimination ability at a 75-day interval between treatments. Prolonged drug intervals to 125 or 175 days delayed tumor evolution but accelerated tumor recurrence. Although 10 mg/kg Q2w had an obvious clinical effect in a short time, it further promotes the progress of resistant population compared with the 3 mg/kg dose. Our model suggests that 480 mg Q4w would be more valuable in terms of clinical efficacy, but complete resistant occurs earlier regardless the interval. IMPLICATIONS: The results of this study emphasize that increasing the dose or shortening the interval between doses accelerates the evolution of heterogeneous populations, although the short-term effect is significant. In practice, the therapeutic regimen should be balanced according to the evolutionary principle.

The effect of PBL combined with comparative nursing rounds on the teaching of nursing for traumatology.

OBJECTIVE: To investigate the effect of problem-based learning (PBL) combined with comparative nursing rounds on the teaching of nursing for traumatology. METHODS: This prospective study was performed in 186 nursing student interns. According to a random number table, these interns were assigned to the control group (n=93) and the experimental group (n=93). In the control group, the interns received traditional teaching methods. Meanwhile, interns in the experimental group received PBL combined with comparative nursing rounds teaching. The level of teaching approval, excellent and good rate of theoretical knowledge, operational ability, medical record writing, and critical thinking disposition inventory-Chinese version scores were compared between the two groups. RESULTS: Teaching approval in learning initiative, problem solving ability, critical thinking, clinical work ability, independent information acquisition ability, and teamwork spirit in the experimental group were improved compared with the control group (all P<0.05). The excellent and good rate of theoretical knowledge, operational ability, and medical record writing in the experimental group were all higher than those in the control group (all P<0.05). Compared with the control group, critical thinking disposition inventory-Chinese version scores in all aspects in the experimental group after training were improved (all P<0.05). CONCLUSION: The application of PBL combined comparative nursing rounds in the teaching of nursing for traumatology is beneficial for a significant improvement in the grasp of theoretical knowledge, operational ability, critical thinking ability, and teaching approval.

Long non-coding RNA in bladder cancer.

Bladder cancer (BC) is the ninth most common malignant disease and ranks fourteenth in cancer mortality worldwide. Moreover, among cancers, the incidence and mortality of BC in males increased to the 6th and 9th place, respectively. The overall survival (OS) declines dramatically as the cancer progresses, especially when urothelial cells transition from noninvasive to invasive. It is well known that epithelial cells can acquire invasive properties and a propensity to metastasize through the epithelial-to-mesenchymal transition (EMT) process in tumourigenesis and progression. However, the potential molecular mechanisms and key pathways are still unclear. As the sequencing technology advances, long non-coding RNAs (lncRNAs) have been proven to play an important role in regulating biological processes and cellular pathways. Here, we reviewed important lncRNAs, such as H19, UCA1 and MALAT1, that participate in the malignant phenotype of BC and regulate EMT signalling networks in the invasion-metastasis cascade during BC development. We further discuss MALAT1, PCAT-1 and SPRY4-IT1, and also urine and blood exosomal H19 and PTENP as potential noninvasive biomarkers. Moreover, antisense oligonucleotides (ASOs) and a double-stranded DNA plasmid (BC-819) have been designed for use in preclinical cancer models and clinical trials in patients. Therefore, the results of investigations have gradually prompted the utility of lncRNAs.

Clinicopathological and Prognostic Role of STAT3/p-STAT3 in Breast Cancer Patients in China: A Meta-Analysis.

In order to explore the important factors in the diagnosis of breast cancer in China, meta-analysis of previous studies was performed to understand the association between STAT3/p-STAT3 and breast cancer. Information about STAT3/p-STAT3 expression and clinical data about breast cancer in China in particular were gathered from PubMed, Web of Science, CNKI and WanFang databases. RevMan 5.3 and STATA 14.0 were used to analyze the occurrence, development and metastasis of breast cancer for 2818 patients in 18 studies. STAT3/p-STAT3 expression was higher in breast cancer tissue than in normal ones (OR = 7.48, 95% CI = 5.64-9.94), in highly differentiated breast cancer tissue than in lowly differentiated cancer tissues (OR = 2.13, 95% CI = 1.53-2.98), in III/IV stage breast cancer than in I/II stage breast cancer (OR = 3.58, 95% CI = 2.44-5.25), and in tissue with lymphatic metastasis than in normal tissues (OR = 3.72, 95% CI = 2.59-5.35), respectively. Thus, the expression of STAT3/p-STAT3 plays a clinicopathological and prognostic role in the diagnosis and treatment of Chinese breast cancer patients.

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade.

BACKGROUND/AIMS: Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. METHODS: We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. RESULTS: We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. CONCLUSION: Our findings revealed the significant role of lncRNAs in the development process of bladder cancer.

Effects of early enteral nutrition on T helper lymphocytes of surgical septic patients: A retrospective observational study.

The aim of this study was to investigate the effects of early enteral nutrition (EEN) on T helper lymphocytes and the subpopulations ratios of surgical septic patients.We performed a retrospective study including 107 eligible patients from February 2014 to December 2015. Patients were divided into EEN, delayed enteral nutrition (DEN), or total parenteral nutrition (TPN) group according to the duration before enteral feeding. Th1, Th2, Th17, and Treg lymphocyte percentages were collected on days 3, 7, and 14 after admission. The disease severity and clinical outcome variables were also recorded.The Th1, Th17 percentages, and Th1/Th2, Th17/Treg ratios of EEN group were significantly lower than those of DEN or TPN group on the 14th day after admission (P < .05). Compared with TPN, DEN might have a tendency to decrease the Th1 and Th17 percentages. EEN could improve the disease severity and clinical outcomes of septic patients, however, no difference on 28-day mortality was found between EEN and DEN group.EEN could improve the dysregulation of Th1/Th2 and Th17/Treg ratios during early stage of sepsis. Compared with DEN, EEN could improve the disease severity and clinical outcomes, but not decrease the 28-day mortality of surgical septic patients.

Adenosine effectively restores endotoxin-induced inhibition of human neutrophil chemotaxis via A1 receptor-p38 pathway.

Neutrophil chemotaxis plays an essential role in recruiting neutrophils to sites of inflammation. Neutrophil chemotaxis is suppressed both after exposure to lipopolysaccharide (LPS) in vitro and during clinical and experimental endotoxemia, leading to serious consequences. Adenosine (ADO) is a potent anti-inflammatory agent that acts on a variety of neutrophil functions. However, its effects on human neutrophil chemotaxis during infection have been less well characterized. In the present study, we investigated the effect of ADO and its receptor-specific antagonist and agonist on neutrophil chemotaxis in an in vitro LPS-stimulated model. The results showed that increasing the concentration of ADO effectively restored the LPS-inhibited neutrophil chemotaxis to IL-8. A similar phenomenon occurred after intervention with a selective A1 receptor agonist but not with a selective antagonist. Pre-treatment with cAMP antagonist failed to restore LPS-inhibited chemotaxis. Furthermore, protein array and western blot analysis showed that the activation of A1 receptor significantly decreased LPS-induced p38 MAPK phosphorylation. However, the surface expression of the A1 receptor in LPS-stimulated neutrophils was not significantly changed. Taken together, these data indicated that ADO restored the LPS-inhibited chemotaxis via the A1 receptor, which downregulated the phosphorylation level of p38 MAPK, making this a promising new therapeutic strategy for infectious diseases.

miR-21 predicts poor prognosis in patients with osteosarcoma.

BACKGROUND AND AIMS: miR-21 has been demonstrated to play an important role in tumour progression. The aim of the present study was to analyse the correlation between miR-21 expression level and clinicopathologic features, as well as to assess the prognostic significance of miR-21 in osteosarcoma. METHODS: Eighty-four pairs of osteosarcoma and corresponding non-cancerous bone tissues were obtained, and miR-21 expression levels were detected using quantitative real-time PCR (qRT-PCR). A χ2 test was used to assess the relationship between miR-21 expression and clinicopathological features. Overall survival (OS) and disease-free survival (DFS) rates were determined by the Kaplan-Meier method and analysed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis. RESULTS: qRT-PCR indicated that miR-21 expression in tumour tissues was strongly elevated compared with the adjacent corresponding non-cancerous bone tissue (7.88 ± 1.04 vs. 1.12 ± 0.37, respectively; P < 0.001). High miR-21 expression levels were linked to advanced clinical stage (P = 0.001), distant metastasis (P = 0.001), high tumour grade (P = 0.032) and large-sized tumours (P = 0.013). A higher miR-21 expression was significantly linked to shorter OS and DFS (both P < 0.001). Furthermore, a multivariate analysis confirmed that miR-21 was an independent and significant prognostic factor to predict poor OS and DFS (both P < 0.001). CONCLUSIONS: Upregulation of miR-21 was associated with poor clinicopathological characteristics. It is used as a marker of poor prognosis in patients with osteosarcoma.

Effects of Varieties, Producing Areas, Ears, and Ear Positions of Single Maize Kernels on Near-Infrared Spectra for Identification and Traceability.

The effects of varieties, producing areas, ears, and ear positions of maize on near-infrared (NIR) spectra were investigated to determine the factors causing the differences in NIR fingerprints of maize varieties. A total of 130 inbred lines were grown in two regions in China, and 12,350 kernel samples were analyzed through NIR spectroscopy. Spectral differences among varieties, producing areas, ears, and ear positions were determined and compared on the basis of pretreated spectra. The bands at 1300-1470, 1768-1949, 2010-2064, and 2235-2311 nm were mainly affected by the producing area. Band selection and principal component analysis were applied to improve the influence of variety on NIR spectra by processing the pretreated spectra. The degrees of the influence of varieties, producing areas, ears, and ear positions were calculated, and the percentages of the influence of varieties, producing areas, ears, and ear positions were 45.40%, 42.66%, 8.22%, and 3.72%, respectively. Therefore, genetic differences among maize inbred lines are the main factors accounted for NIR spectral differences. Producing area is a secondary factor. These results could provide a reference for researchers who authenticate varieties, perform geographical origin traceabilities, and conduct maize seed breeding.

Role of α-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury.

αII-spectrin breakdown products are regarded as potential biomarkers for traumatic brain injury (TBI). The aim of the present study was to further evaluate these biomarkers by assessing their clinical utility in predicting the severity of injury and clinical outcome of patients with TBI. Eligible patients with acute TBI (n=17), defined by a Glasgow Coma Scale (GCS) score of ≤8, were enrolled. Ventricular cerebrospinal fluid (CSF) was sampled from each patient at 24, 72 and 120 h following TBI. An immunoblot assay was used to determine the concentrations of SBDPs in the CSF samples. The concentrations of SBDPs combined with the GCS score at 24 h after injury and the Glasgow Outcome Score (GOS) at 30 days after injury were compared and analyzed. The levels of SBDPs in CSF were markedly increased following acute TBI in comparison with those in the control group. In the early period after TBI, the levels of SBDPs were closely associated with GCS score. Comparisons of the SBDP levels with the severity of injury revealed significant differences between patients with the most severe brain injury and patients with severe brain injury in the first 24 h post-injury (P<0.05). The levels and dynamic changes of SBDPs in CSF exhibited a close association with GOS at 30 days after injury. The levels of SBDPs differed significantly between patients grouped according to prognosis (P<0.05). These results suggest that in the early period after TBI, the levels and dynamic changes of SBDPs in CSF can be useful in the prediction of the severity of injury and clinical outcome of patients.

SERPINE1 rs1799768 polymorphism contributes to sepsis risk and mortality.

INTRODUCTION: The present meta-analysis aimed to investigate whether there is an association between SERPINE1 rs1799768 polymorphism and sepsis risk and mortality. MATERIALS AND METHODS: Published reports were searched in PubMed, PubMed Central, Gene, PubChem and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed in a random-effects model. RESULTS: The results of the overall meta-analysis indicated that an increased sepsis risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.30; 95% CI 1.08-1.56; p = 0.006). When studies were stratified by ethnicity, no significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk in the Asian group. As for the Caucasian population, overall OR was 1.24 (95% CI 1.02-1.51; p = 0.03). The results of the overall meta-analysis indicated that an increased sepsis mortality risk was evidently associated with SERPINE1 rs1799768 polymorphism (OR = 1.73; 95% CI 1.31-2.28; p < 0.0001). When studies were stratified by ethnicity, significant association was observed between SERPINE1 rs1799768 polymorphism and sepsis risk mortality in the Asian group and the Caucasian population. CONCLUSIONS: In conclusion, the meta-analysis suggests that there are significant associations between SERPINE1 rs1799768 polymorphism and risk of sepsis and sepsis mortality.

Risk factors and prognosis of hypoalbuminemia in surgical septic patients.

The aim of this study was to investigate the risk factors of hypoalbuminemia and effects of different albumin levels on the prognosis of surgical septic patients. We preformed a retrospective clinical study including 135 adult patients from September 2011 to June 2014. The albumin levels and severity markers were recorded during the first 48 h after enrollment, and logistic regression analyses were used to determine the risk factors. The outcomes of patients with different albumin levels were also compared. The acute physiology and chronic health evaluation II (APACHE II) score (OR 1.786, 95% CI [1.379-2.314], P < 0.001), C-reactive protein (CRP) (OR 1.016, 95% CI [1.005-1.027], P = 0.005), and blood lactate (OR 1.764, 95% CI [1.141-2.726], P = 0.011) were established as the independent risk factors of hypoalbuminemia in patients with surgical sepsis. The severity markers and outcomes of patients with albumin levels ≤20 g/L were significantly worse than that of 21-25 g/L and ≥26 g/L, whereas the latter two groups had similar prognosis. Every 1 g/L decrease of albumin level below the optimal cut-off (23 g/L) was associated with a 19.4% increase in hospital mortality and a 28.7% increase in the incidence of multiple organ dysfunction syndrome. In conclusion, APACHE II score (≥14.5), CRP (≥34.25 mg/L), and blood lactate (≥.35 mmol/L) were established as the independent risk factors of hypoalbuminemia in the early stage of surgical sepsis. Patients with baseline albumin level ≤20 g/L had worse prognosis than that of albumin level ≥21 g/L. Albumin levels were negatively correlated the prognosis of surgical sepsis when below about 23 g/L.

Circulating Histone Levels Reflect Disease Severity in Animal Models of Acute Pancreatitis.

OBJECTIVES: Extracellular histones are rapidly cleared by the liver and rarely detectable in the circulation unless there is extensive cell death, as in severe trauma and sepsis. This study investigated whether circulating histones are elevated in experimental acute pancreatitis models and correlate to disease severity. METHODS: Acute pancreatitis was induced in mice by: (1) 4 or (2) 12 intraperitoneal injections of cerulein (50 µg/kg) at 1 hour apart; (3) retrograde infusion of 3.5% sodium taurocholate into the biliopancreatic duct. Mice were sacrificed at various time points to collect blood and tissues. Severity of pancreatitis was assessed by biochemical markers and histopathology. Circulating histones were determined by Western blotting. RESULTS: Four cerulein injections induced edematous pancreatitis, whereas 12 cerulein injections and ductal taurocholate infusion caused necrotizing pancreatitis. Circulating histones were barely detectable in the blood of animals with edematous pancreatitis but significantly increased in necrotizing pancreatitis. The levels of circulating histones were strongly correlated to histopathological scores of necrosis of the pancreas. CONCLUSIONS: Circulating histones increased significantly in necrotizing pancreatitis due to extensive pancreatic acinar cell death. Levels of circulating histones may have translational potential as a biomarker of disease severity.