Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-ß (TGF-ß) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-ß pathway.

Phenotypic heterogeneity unveils a negative correlation between antibiotic resistance and quorum sensing in Pseudomonas aeruginosa clinical isolates.

Colonization of Pseudomonas aeruginosa in the lung environments frequently leads to the enrichment of strains displaying enhanced antibiotic resistance and reduced production of quorum-sensing (QS) controlled products. However, the relationship between the emergence of QS deficient variants and antibiotic resistance remains less understood. In this study, 67 P. aeruginosa strains were isolated from the lungs of 14 patients with chronic obstructive pulmonary disease, followed by determining their genetic relationship, QS-related phenotypes and resistance to commonly used antibiotics. The integrity of P. aeruginosa QS system was checked by DNA sequencing. The relationship between the QS system and antibiotic resistance was then assessed by correlation analyses. The function of the LasR protein and bacterial virulence were evaluated through homology modeling and nematode-infection assay. The influence of antibiotic on the development of extracellular protease production ability of P. aeruginosa was tested by an evolutionary experiment. The results showed that P. aeruginosa clinical strains displayed abundant diversity in phenotype and genotype. The production of extracellular proteases was significantly negatively correlated with antibiotic resistance. The strains with enhanced antibiotic resistance also showed a notable overlap with the mutation of lasR gene, which is the core regulatory gene of P. aeruginosa QS system. Molecular docking and Caenorhabditis elegans infection assays further suggested that P. aeruginosa with impaired LasR protein could also have varying pathogenicity. Moreover, in vitro evolution experiments demonstrated that antibiotic-mediated selective pressure, particularly from Levofloxacin contributed to the emergence of extracellular protease-negative strains. Therefore, this study provides evidence for the connection of P. aeruginosa QS system and antibiotic resistance, and holds significance for developing targeted strategies to address antibiotic resistance and improving the management of antibiotic-resistant infections in chronic respiratory diseases.

Resistance Transition of Pseudomonas aeruginosa in SARS-CoV-2-Uninfected Hospitalized Patients in the Pandemic.

Objective: To investigate the impact of coronavirus disease 2019 (COVID-19) specified preventive and control measures on the distribution and resistance transition of Pseudomonas aeruginosa (P. aeruginosa) in uninfected hospitalized patients during the pandemic. Methods: This retrospective study retrieved data from 316 P. aeruginosa isolates in the year pre-COVID-19 (n=131) pandemic and the year under COVID-19 specified preventive and control (post-pandemic year, n=185), compared the general characteristics, laboratory results, and antimicrobial susceptibility tests of P. aeruginosa between the two groups. Results: Compared with the pre-pandemic year, the isolation rate of P. aeruginosa (14.35% vs 22.31%, P<0.001) increased, while the rate of drug resistant P. aeruginosa decreased significantly (29.77% vs 19.45%, P<0.001) in the post-pandemic year; Prescription of ß-Lactams (30.5% vs 50.0%, P<0.01) also increased significantly. The resistance rates of P. aeruginosa isolates to ceftazidime (P<0.01), ciprofloxacin (P<0.01), and gentamicin (P<0.001) increased, whereas the resistance rates to piperacillin/tazobactam (P<0.01) and imipenem (P<0.05) decreased significantly. Conclusion: The COVID-19 specified preventive and control measures have influenced the distribution and resistance transition of P. aeruginosa, further verifications are needed in future research.

Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung.

Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.

Diagnostic and prognostic value of Ang-2 in ARDS: a systemic review and meta-analysis.

BACKGROUND: To investigate the diagnostic and prognostic value of angiopoietin-2 (Ang-2) for acute respiratory distress syndrome (ARDS). METHODS: Seven databases (4 English and 3 Chinese databases) were searched, the quality was evaluated by QUADAS-2 and GRADE profile. The bivariate model was employed to combine area under the curve (AUC), pooled sensitivity (pSEN) and pooled specificity (pSPE), the Fagan's nomogram was employed for evaluating clinical utility. This study was registered in PROSPERO (NO.CRD42022371488). RESULTS: 18 eligible studies comprising 27 datasets (12 diagnostic and 15 prognostic datasets) were included for meta-analysis. For diagnostic analysis, Ang-2 yielded an AUC of 0.82, with a pSEN of 0.78 and a pSPE of 0.74; in clinical utility analysis, a pretest probability of 50% regulated the post probability positive (PPP) of 75% and the post probability negative (PPN) of 23%. In prognostic analysis, Ang-2 yielded an AUC of 0.83, with a pSEN of 0.69, a pSPE of 0.81, and good clinical utility (a pretest probability of 50% regulated the PPP of 79% and the PPN of 28%). Heterogeneity existed in both diagnostic and prognostic analysis. CONCLUSIONS: Ang-2 demonstrates promising diagnostic and prognostic capabilities as a noninvasive circulating biomarker for ARDS, especially in the Chinese population. It is advisable to dynamically monitor Ang-2 in critically ill patients both suspected and with confirmed ARDS.

Pathogen Distribution, Drug Resistance Risk Factors, and Construction of Risk Prediction Model for Drug-Resistant Bacterial Infection in Hospitalized Patients at the Respiratory Department During the COVID-19 Pandemic.

Objective: To investigate the distribution and drug resistance of pathogens among hospitalized patients in the respiratory unit during the COVID-19 pandemic, analyze the risk factors of drug resistance, construct a risk prediction model. Methods: This study isolated 791 strains from 489 patients admitted to the Affiliated Hospital of Chengdu University, who were retrospectively enrolled between December 2019 and June 2021. The patients were divided into training and validation sets based on a random number table method (8:2). The baseline information, clinical characteristics, and culture results were collected using an electronic database and WHONET 5.6 software and compared between the two groups. A risk prediction model for drug-resistant bacteria was constructed using multi-factor logistic regression. Results: K. pneumoniae (24.78%), P. aeruginosa (17.19%), A. baumannii (10.37%), and E. coli (10.37%) were the most abundant bacterial isolates. 174 isolates of drug-resistant bacteria were collected, ie, Carbapenem-resistant organism-strains, ESBL-producing strains, methicillin-resistant S. aureus, multi-drug resistance constituting 38.51%, 50.57%, 6.32%, 4.60%, respectively. The nosocomial infection prediction model of drug-resistant bacteria was developed based on the combined use of antimicrobials, pharmacological immunosuppression, PCT>0.5 ng/mL, CKD stage 4-5, indwelling catheter, and age > 60 years. The AUC under the ROC curve of the training and validation sets were 0.768 (95% CI: 0.624-0.817) and 0.753 (95% CI: 0.657-0.785), respectively. Our model revealed an acceptable prediction demonstrated by a non-significant Hosmer-Lemeshow test (training set, p=0.54; validation set, p=0.88). Conclusion: K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli were the most abundant bacterial isolates. Antimicrobial resistance among the common isolates was high for most routinely used antimicrobials and carbapenems. COVID-19 did not increase the drug resistance pressure of the main strains. The risk prediction model of drug-resistant bacterial infection is expected to improve the prevention and control of antibacterial-resistant bacterial infection in hospital settings.

Dockey: a modern integrated tool for large-scale molecular docking and virtual screening.

Molecular docking is a structure-based and computer-aided drug design approach that plays a pivotal role in drug discovery and pharmaceutical research. AutoDock is the most widely used molecular docking tool for study of protein-ligand interactions and virtual screening. Although many tools have been developed to streamline and automate the AutoDock docking pipeline, some of them still use outdated graphical user interfaces and have not been updated for a long time. Meanwhile, some of them lack cross-platform compatibility and evaluation metrics for screening lead compound candidates. To overcome these limitations, we have developed Dockey, a flexible and intuitive graphical interface tool with seamless integration of several useful tools, which implements a complete docking pipeline covering molecular sanitization, molecular preparation, paralleled docking execution, interaction detection and conformation visualization. Specifically, Dockey can detect the non-covalent interactions between small molecules and proteins and perform cross-docking between multiple receptors and ligands. It has the capacity to automatically dock thousands of ligands to multiple receptors and analyze the corresponding docking results in parallel. All the generated data will be kept in a project file that can be shared between any systems and computers with the pre-installation of Dockey. We anticipate that these unique characteristics will make it attractive for researchers to conduct large-scale molecular docking without complicated operations, particularly for beginners. Dockey is implemented in Python and freely available at https://github.com/lmdu/dockey.

Identification of a Multidrug Resistant Pseudomonas aeruginosa Isolate Harboring Infrequent Red Fluorescence Plasmid from COPD Patient.

Pseudomonas aeruginosa is a notorious Gram-negative opportunistic pathogen that normally causes acute and chronic infections in a wide range of hosts. In this study, a multi-resistant P. aeruginosa isolate L1a harboring an infrequent plasmid with red fluorescence was obtained from the bronchoalveolar lavage fluid of a patient with chronic obstructive pulmonary disease. The results of susceptibility testing and virulence-related phenotypic identification revealed that P. aeruginosa L1a was resistant to levofloxacin, cefepime, aztreonam, and imipenem and showed significantly stronger capacities for swimming and pyocyanin production than the reference strain PAO1. The genome of P. aeruginosa L1a was assembled into one circular chromosome (6,216,913 bp) and one circular plasmid (9111 bp). P. aeruginosa L1a was found to belong to the multilocus sequence type ST549, and serotype O5, and carried 8 drug resistance genes and 18 multidrug efflux pump-related genes in the chromosomal DNA. The plasmid pL1a harbored a tetracycline resistant gene tetA and a functional red fluorescence protein. This study reports a multidrug resistant P. aeruginosa clinical isolate harboring an infrequent red fluorescence plasmid for the first time.

Repurposing Dimetridazole and Ribavirin to disarm Pseudomonas aeruginosa virulence by targeting the quorum sensing system.

Pseudomonas aeruginosa relies on its complex cellular regulatory network to produce a series of virulence factors and to cause various acute and chronic infections in a wide range of hosts. Compared with traditional antibiotics which frequently accompany with widespread antibiotic resistance, crippling the virulence system of bacteria is expected to be a promising anti-infective strategy. In this study, Dimetridazole and Ribavirin, which had poor antibacterial activities on P. aeruginosa reference isolate PAO1 in nutrient medium but significantly inhibited the growth of P. aeruginosa PAO1 in M9-adenosine, were selected from 40 marketed compounds with similar core structure (furan, benzofuran, or flavonoids) to the acyl-homoserine lactone signals of P. aeruginosa quorum sensing (QS) system. The production of QS-controlled proteases, pyocyanin, and biofilm formation of P. aeruginosa PAO1 and the clinical isolates were significantly decreased by the presence of Dimetridazole or Ribavirin. Correspondingly, the majority of QS-activated genes in P. aeruginosa, including the key regulatory genes lasR, rhlR, and pqsR and their downstream genes, were significantly inhibited by Ribavirin or Dimetridazole, as determined by RNA-sequencing and quantitative PCR. Furthermore, the susceptibilities of drug-resistant P. aeruginosa isolates to polymyxin B, meropenem, and kanamycin were remarkably promoted by the synergistic application of Dimetridazole or Ribavirin. Finally, the treatment of Ribavirin or Dimetridazole effectively protected Caenorhabditis elegans and mice from P. aeruginosa infection. In conclusion, this study reports the antivirulence potentials of Dimetridazole and Ribavirin on P. aeruginosa and provides structural basis and methodological reference for the development of anti-pseudomonal drugs.

Primary or metastatic lung cancer? Sebaceous carcinoma of the thigh: A case report.

BACKGROUND: Sebaceous carcinoma (SC), a malignancy primarily characterized by aggressive growth, affects cutaneous tissues of the periocular region. Extraocular SC is extremely rare, especially in the extremities, as evidenced by only a handful of reported cases. CASE SUMMARY: A 65-year-old man presented with a rapidly enlarging swelling on the left inner thigh, which was initially misdiagnosed as a subcutaneous abscess. The lesion had appeared two months prior to admission. Clinical examination revealed a cauliflower-like swollen content, with an ulcerated and infected mass located on his left thigh. At the same time, we observed solitary nodular lesions in his lungs and brain, with biopsy pathology of the lung lesions found to be consistent with the mass in the thigh. The patient received chemotherapy comprising cis-platinum with fluorouracil, followed by targeted therapy with anlotinib hydrochloride and chemotherapy with vinorelbine, implantation of iodine-125 seeds in the thigh and pulmonary tumor. The initial stage intervention achieved partial remission. The efficacy of maintenance treatment was evaluated as stable disease after the first 5 cycles; however, the patient developed a new brain lesion after the sixth cycle of treatment, which resulted in progressive disease and he received whole brain gamma knife radiotherapy. CONCLUSION: We analyzed the clinical presentation, imaging features, pathology and treatment of a rare case of lung, brain and lymph node metastasis of SC located in the thigh. It is evident that cis-platinum combined with fluorouracil, vinorelbine combined with anlotinib hydrochloride may be an effective therapeutic regimen in advanced SC. However, brain metastatic lesions should receive early radiotherapy.

IL-1ß-Triggered Long Non-coding RNA CHRF Induces Non-Small Cell Lung Cancer by Modulating the microRNA-489/Myd88 Axis.

Background: Long noncoding RNAs (LncRNAs) possess crucial roles in carcinogenesis. The current study aims to evaluate the effects of interleukin-1ß (IL-1ß)-mediated lncRNA cardiac hypertrophy-related factor (CHRF)/microRNA-489 (miR-489)/myeloid differentiation factor 88 (Myd88) on non-small-cell lung cancer (NSCLC). Methods: Initially, the expression of IL-1ß and lncRNA CHRF in NSCLC cells and tissues was determined, respectively. H460 cell line with highest lncRNA CHRF expression was selected for in vitro experimentations. Afterward, the interaction among lncRNA CHRF, miR-489, and Myd88 was verified with their significance in cell functions and tumorigenicity and lung metastasis analyzed following. Results: IL-1ß and lncRNA CHRF was remarkably upregulated in NSCLC. IL-1ß was able to elevate lncRNA CHRF expression. Additionally, lncRNA CHRF targeted miR-489 and miR-489 targeted Myd88. Moreover, functional assay results suggested that under IL-1ß treatment, lncRNA CHRF induced NSCLC cell malignant properties and tumorigenicity and lung metastasis through modulation of miR-489/Myd88 axis. Conclusion: Taken together, our findings revealed that IL-1ß-induced elevation of lncRNA CHRF aggravated NSCLC through modulation of miR-489/Myd88 axis, which provides a novel direction for NSCLC therapy development.

Subinhibitory Cefotaxime and Levofloxacin Concentrations Contribute to Selection of Pseudomonas aeruginosa in Coculture with Staphylococcus aureus.

Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental cues. Pseudomonas aeruginosa and Staphylococcus aureus are two common bacterial pathogens frequently coisolated from patients with burns and respiratory disease. Whether the application of commonly used antibiotics influences the interaction dynamics of the two species still remains largely unexplored. By performing a series of on-plate competition assays and RNA sequencing-based transcriptional profiling, we showed that the presence of the cephalosporin antibiotic cefotaxime or the quinolone antibiotic levofloxacin at subinhibitory concentration contributes to selecting P. aeruginosa from the coculture with S. aureus by modulating the quorum-sensing (QS) system of P. aeruginosa. Specifically, a subinhibitory concentration of cefotaxime promotes the growth suppression of S. aureus by P. aeruginosa in coculture. This process may be related to the increased production of the antistaphylococcal molecule pyocyanin and the expression of lasR, which is the central regulatory gene of the P. aeruginosa QS hierarchy. On the other hand, subinhibitory concentrations of levofloxacin decrease the competitive advantage of P. aeruginosa over S. aureus by inhibiting the growth and the las QS system of P. aeruginosa. However, pqs signaling of P. aeruginosa can be activated instead to overcome S. aureus. Therefore, this study contributes to understanding the interaction dynamics of P. aeruginosa and S. aureus during antibiotic treatment and provides an important basis for studying the pathogenesis of polymicrobial infections. IMPORTANCE Increasing evidence has demonstrated the polymicrobial characteristics of most chronic infections, and the frequent communications among bacterial pathogens result in many difficulties for clinical therapy. Exploring bacterial interspecific interaction during antibiotic treatment is an emerging endeavor that may facilitate the understanding of polymicrobial infections and the optimization of clinical therapies. Here, we investigated the interaction of cocultured P. aeruginosa and S. aureus with the intervention of commonly used antibiotics in clinic. We found that the application of subinhibitory concentrations of cefotaxime and levofloxacin can select P. aeruginosa in coculture with S. aureus by modulating P. aeruginosa QS regulation to enhance the production of antistaphylococcal metabolites in different ways. This study emphasizes the role of the QS system in the interaction of P. aeruginosa with other bacterial species and provides an explanation for the persistence and enrichment of P. aeruginosa in patients after antibiotic treatment and a reference for further clinical therapy.

Eosinophilic phenotype was associated with better early clinical remission in elderly patients but not middle-aged patients with acute exacerbations of COPD.

BACKGROUND: There is limited evidence of the relationship between peripheral blood eosinophils and clinical remission of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) at different ages, especially in elderly patients, which was the objective of the present study. METHODS: This retrospective study stratified patients by age (elderly patients >65 years old or middle-aged patients between 45 and 65 years old) and analysed the relationship between blood eosinophils (≥2% or <2%) and AECOPD clinical remission at observing time points of 7, 14, 21 and 28 days of hospitalisation. Student's t tests, Mann-Whitney U tests, Chi-squared or Fisher's exact tests were conditionally used to compare difference between groups. The unadjusted or adjusted Cox proportional hazards model was used to analyse the association between blood eosinophilic levels and cumulative clinical remission. RESULTS: Of 703 AECOPD cases analysed, 616 were elderly people (>65 years), 312 of whom had eosinophilic exacerbations. There were statistically significant differences in leucocytes, eosinophils, neutrophils, lymphocytes, monocytes, high-sensitivity C-reactive protein levels (hs-CRP), and hospital costs between groups (P < .05, respectively). According to the chi-square analysis, eosinophilic exacerbation had a higher clinical remission rate at 7, 14 and 21 days (all P < .05), but not 28 days (P > .05). Among analysis through adjusted Cox proportional hazards model, eosinophilic exacerbation was significantly associated with a higher cumulative remission rate in elderly patients at 7, 14, 21 days (all P < .05), but not 28 days (P > .05). No significant association was observed in meddle-aged patients at any time points (all P > .05). CONCLUSION: Eosinophilic exacerbation was associated with better early clinical remission of AECOPD patients during hospitalisation. As stratified by ages, similar results were observed in elderly patients but not middle-aged patients. Blood eosinophils at different ages may be valuable in personalised management for AECOPD.

Circulating microRNA-145 as a diagnostic biomarker for non-small-cell lung cancer: A systemic review and meta-analysis.

BACKGROUND: MicroRNAs (miRNAs), a class of small non-coding, highly stable RNAs, have been reported to have diagnostic value for variety types of cancers. OBJECTIVES: To assess the diagnostic value of circulating miR-145 for non-small cell lung cancer (NSCLC) by using systemic review and meta-analysis. METHODS: A systematic literature search was conducted in five databases until 20 February 2020 to identify diagnostic trials of miR-145 in the diagnosis of NSCLC. The quality of included studies was assessed by the QUADAS-2 tool with Review Manager 5.3, and the summary receiver operating characteristic (SROC) curve was plotted by STATA 13.1 software. RESULTS: A total of 1394 patients from 11 data sets in trials (published in nine studies) were recruited. The area under the curve of the SROC was 0.83. According to the meta regression, the specimen selection was considered the source of heterogeneity, the SROC in serum (0.90 (95% CI 0.87, 0.92), the sensitivity was 0.84 (95% CI 0.79, 0.89), and the specificity was 0.80 (95% CI 0.71, 0.89)) was obviously higher than that in plasma (SROC=0.75). CONCLUSION: Serum miR-145 might be served as a potentially useful biomarker for NSCLC diagnosis. However, due to the existing limited-quality research, more large-scale and multicenter studies are required for further verification.

Serum Endostatin Is a Novel Marker for COPD Associated with Lower Lung Function, Exacerbation and Systemic Inflammation.

Backgrounds and Aims: It is well known that angiogenesis contributes to the progression of chronic obstructive pulmonary disease (COPD) by initiating the remodeling of bronchial vasculature. However, the specific molecular mechanisms are incompletely understood. This research aimed to explore whether endostatin, a member of endogenous antiangiogenic proteins, is a biomarker in COPD and plays a role in the angiogenesis of COPD. Methods: 100 stable COPD patients, 130 patients with acute exacerbation (AECOPD) and 68 healthy volunteers were recruited in this research. Lung function test was conducted in the healthy people and stable COPD patients. Serum endostatin, C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) of all the subjects were measured by Human Magnetic Luminex Screening Assay. Results: Serum endostatin level was significantly higher in stable COPD compared with healthy control and even more in AECOPD patients (P<0.001). Besides, stable COPD patients with frequent exacerbation (≥2 exacerbations per year) in the last 1 year had a higher concentration of endostatin in the circulation compared to the patients with less exacerbation (P=0.037). Furthermore, circulatory endostatin was negatively associated with forced expiratory volume in 1 s % predicted (FEV1%pre), an index of lung function in the stable COPD group (P=0.009). Finally, endostatin was positively correlated to serum CRP in COPD group (including stable and AECOPD) (P=0.005) and all the subjects (P<0.001), but only associated with VEGF in the total participants (P=0.002), not in the COPD group. Conclusion: These results suggested that endostatin is a biomarker for COPD and associated with lower lung function, exacerbation, and systemic inflammation. Endostatin potentially contributes to the pathogenesis of COPD.

Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD.

Introduction: Patients with COPD often show increased systemic inflammation which is associated with lower functional status, greater exacerbation risk, and worse clinical outcomes. Syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs), have been found to involve in inflammatory processes in many chronic inflammatory diseases. The aim of this preliminary clinical study was to investigate the possible association between two SDCs, SDC-1 and SDC-4, with lung function, systemic inflammation, and risk of exacerbations in COPD patients. Method: Serum SDC-1 and SDC-4 levels were measured in 101 COPD patients and 57 health controls. Correlations between SDCs and other parameters were analyzed using Spearsman's rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. Results: Although both serum SDC-1 and SDC-4 showed a downward trend in COPD patients, only SDC-1 levels were correlated positively with the ratio of FEV1/FVC and parameters of small airway obstruction. Besides, SDC-1 but not SDC-4, was negatively correlated with C-reactive protein (CRP) in COPD patients and downregulated in frequent exacerbators (FEs) of COPD. Using a cutoff value of 2.08 ng/mL, the sensitivity and specificity of SDC-1 to differentiate FE were 44% and 93.4%, respectively. Conclusion: In conclusion, circulating SDC-1 may be a novel inflammatory biomarker associated with lung function and systemic inflammation in patients with COPD, which could also be useful to identify the risk of COPD exacerbation. Further studies should be performed to clarify the influences of SDC-1 on the pathogenesis and outcomes of COPD.

Time series analysis of temporal trends in the pertussis incidence in Mainland China from 2005 to 2016.

Short-term forecast of pertussis incidence is helpful for advanced warning and planning resource needs for future epidemics. By utilizing the Auto-Regressive Integrated Moving Average (ARIMA) model and Exponential Smoothing (ETS) model as alterative models with R software, this paper analyzed data from Chinese Center for Disease Control and Prevention (China CDC) between January 2005 and June 2016. The ARIMA (0,1,0)(1,1,1)12 model (AICc = 1342.2 BIC = 1350.3) was selected as the best performing ARIMA model and the ETS (M,N,M) model (AICc = 1678.6, BIC = 1715.4) was selected as the best performing ETS model, and the ETS (M,N,M) model with the minimum RMSE was finally selected for in-sample-simulation and out-of-sample forecasting. Descriptive statistics showed that the reported number of pertussis cases by China CDC increased by 66.20% from 2005 (4058 cases) to 2015 (6744 cases). According to Hodrick-Prescott filter, there was an apparent cyclicity and seasonality in the pertussis reports. In out of sample forecasting, the model forecasted a relatively high incidence cases in 2016, which predicates an increasing risk of ongoing pertussis resurgence in the near future. In this regard, the ETS model would be a useful tool in simulating and forecasting the incidence of pertussis, and helping decision makers to take efficient decisions based on the advanced warning of disease incidence.

VIKOR method with enhanced accuracy for multiple criteria decision making in healthcare management.

Visekriterijumsko kompromisno rangiranje (VIKOR) method is one of the commonly used multi criteria decision making (MCDM) methods for improving the quality of decision making. VIKOR has an advantage in providing a ranking procedure for positive attributes and negative attributes when it is used and examined in decision support. However, we noticed that this method may failed to support an objective result in medical field because most medical data have normal reference ranges (e.g., for normally distributed data: NRR ∈ [µ ± 1.96σ], this limitation shows a negative effect on the acceptance of it as an effective decision supporting method in medical decision making. This paper proposes an improved VIKOR method with enhanced accuracy (ea-VIKOR) to make it suitable for such data in medical field by introducing a new data normalization method taking the original distance to the normal reference range (ODNRR) into account. In addition, an experimental example was presented to demonstrate efficiency and feasibility of the ea-VIKOR method, the results demonstrate the ability of ea-VIKOR to deal with moderate data and support the decision making in healthcare care management. For this reason, the ea-VIKOR should be considered for use as a decision support tool for future study.