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Background Mycobacterium fortuitum is a rapidly growing non-tuberculous mycobacterium (NTM) with weak pathogenicity. Here, we present a rare case of disseminated M. fortuitum and Talaromyces marneffei coinfection in a human immunodeficiency virus (HIV) negative patient. Case presentation A 28-year-old female was admitted to our hospital due to 2 months of swelling of lymph nodes on the right side of her cervix, accompanied by repeated low fever for more than 1 month. Biopsy of the right cervical lymph node and endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) both suggested granulomatous inflammation. The bacterial culture and mycobacteria examination of the lesion as well as HIV antibody test were all negative. Disseminated T. marneffei infection was diagnosed by the quantitative polymerase chain reaction (qPCR) results from the blood showing 1798 copies/ul. In the meantime, treatment with amphotericin B combined with cefoxitin was administered for suspected NTM infection. However, the once-dropped fever recurred and the lymph nodes continued to swell. Metagenomics next-generation sequencing (mNGS) detection of the lymph nodes indicated M. fortuitum. After combination treatment with amphotericin B, voriconazole, linazolamide, and imipenem, the patient's body temperature returned to normal, the lymph node swelling was gradually reduced, and the lung lesion was absorbed. Conclusion We report the first case of an HIV-negative patient diagnosed with disseminated M. fortuitum and T. marneffei coinfection with nonspecific clinical manifestation, in order to heighten awareness of these infections.

Resistant starch could be degraded by the fermentation of colonic microorganisms in the large intestine of mammals, but not in the small intestine. In this study, we established a novel strategy by using resistant starch as an endogenous marker to determine the glucose absorption of the small intestine of laboratory animals. By optimization of the classical enzymatic method of starch measurement, the demand for the sample weight was reduced by 90%. Moreover, the amount of resistant starch in normal feed was detectable without any extra addition. The value of small intestine glucose absorption of mice was similar when using resistant starch and titanium dioxide as inert markers. The fermentation of resistant starch by intestinal microorganisms in the small intestine was demonstrated not disturbing the detection of glucose absorption significantly. Artificial sweeteners exposed ICR mice showed different glucose absorption which indicated, first, resistant starch can be used as a novel endogenous marker in the small intestine of small animals; second, although glucose tolerance did not change in mice after short-term exposure to artificial sweeteners, there were significant changes in glucose absorption associated with it; third, the short-term exposure resulted in no significant change in glucose tolerance.

In classical microbiology, developing a high-efficiency bacterial consortium is a great challenge for faster biodegradation of petroleum contaminants. In this study, a systematic experimental and mathematical procedure was adopted to establish a bacterial consortium for the effective biodegradation of heavy oil constituents. A total of 27 bacterial consortia were established as per orthogonal experiments, using 8 petroleum-degrading bacterial strains. These bacteria were closer phylogenetic relatives of Brevundimonas sp. Tibet-IX23 (Y1), Bacillus firmus YHSA15, B. cereus MTCC 9817, B. aquimaris AT8 (Y2, Y6 and Y7), Pseudomonas alcaligenes NBRC (Y3), Microbacterium oxydans CV8.4 (Y4), Rhodococcus erythropolis SBUG 2052 (Y5), and Planococcus sp. Tibet-IX21 (Y8), and were used in different combinations. Partial correlation analysis and a general linear model hereafter were applied to investigate interspecific relationships among different strains and consortia. The Y1 bacterial species showed a remarkable synergy, whereas Y3, Y4, and Y6 displayed a strong antagonism in all consortia. Inoculation ratios of different strains significantly influenced biodegradation. An optimal consortium was constructed with Y1, Y2, Y5, Y7, and Y8, which revealed maximum degradation of 11.238 mg/mL OD600 for oil contaminants. This study provides a line of evidence that a functional consortium can be established by mathematical models for improved bioremediation of petroleum-contaminated environment.

Talaromyces (formerly Penicillium) marneffei, a dimorphic fungus, is the most common opportunistic pathogen in human immunodeficiency viruses (HIV)-positive patients, but it rarely appears in HIV-negative individuals. Previously, in 2014, we reported the case of an HIV-negative Chinese woman with disseminated T. marneffei infection within an osteolytic lesion. Subsequently, she was followed up for 6 years, and we present an updated report of her clinical condition during the follow-up period. She presented with T. marneffei infection relapse and nontuberculous mycobacterium (NTM) infection. Laboratory tests showed anti-interferon-gamma (anti-IFN-γ) autoantibody-positive. Antifungals and anti-NTM treatment successfully improved her symptoms and laboratory results. This case highlights the type of infectious diseases that occurs as a result of immunodeficiency syndrome associated with anti-IFN-γ autoantibody. Keywords: Talaromyces marneffei, Osteolytic lesion, Nontuberculous mycobacterium, Anti-interferon-gamma autoantibody

BACKGROUND Primary pulmonary mucosa-associated lymphoma tissue lymphoma is rare and is often misdiagnosed because of its diverse and nonspecific clinical features. The aim of this study was to raise awareness among clinicians and to share our experience of treating and managing such patients. MATERIAL AND METHODS This retrospective study was conducted between 1 January 2009 and 31 October 2017 at the First Affiliated Hospital of Guangxi Medical University. All cases were confirmed via pathology and immunohistochemistry. In addition, we reviewed all relevant literature. RESULTS Altogether, 21 patients (7 female, 14 male) with a median age of 54 (range, 19-84) years were diagnosed with primary pulmonary mucosa-associated lymphoma. Expiratory dyspnea, repeated cough and expectoration, and weight loss were the most common symptoms. Pulmonary lesions were found via physical examination in 10 patients who had no obvious symptoms. Chest computed tomography showed nodules, pulmonary consolidation, bronchial bronchogram, ground-glass opacity, and mediastinal lymph node enlargement. Some patients were misdiagnosed with tuberculosis and pneumonia, while others were initially diagnosed with cancer. Tumor pathology and immunocytochemistry indicated primary pulmonary mucosa-associated lymphoma tissue lymphoma. Six patients underwent chemotherapy, 5 underwent surgery, 4 underwent surgery and chemotherapy, 3 were only observed, and 3 refused treatment. CONCLUSIONS The development of primary pulmonary mucosa-associated lymphoid tissue lymphoma is slow and insidious. Having no specific clinical symptoms and imaging findings, it is easily misdiagnosed. Final diagnosis is made via pathologic evaluation and immunohistochemistry. Surgery and chemotherapy are the primary treatment modalities and yield a good prognosis.

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naive CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.

Background: To observe the effects of inhaled corticosteroids (ICS) and systemic corticosteroids (SCS) on the sputum microbiology of patients with AECOPD.Methods: The 16S rRNA sequencing results for sputum samples from 36 admitted AECOPD patients were analyzed using ICS or SCS on the basis of standard treatment; sputum samples were collected before and after treatment for 1 day, 7, and 14 days.Results: After 7 days of SCS treatment, the bacterial abundance of Sorangium, Acidibacter, and Fretibacterium decreased at the genus level. After 14 days of SCS treatment, the bacterial abundance of Prevotella_2, Bergeyella, Corynebacterium_1, and Ruminococcaceae_UCG-014 was decreased at the genus level, and an increase in the bacterial abundance of the Clostridiales_vadinBB60_group was observed at the family level. The linear discriminant analysis effect size (LEfSe) algorithm showed that after treatment for 14 days, Sphingobacterium increased in the SCS group, and Corynebacterium_1 (genus level), Bacillales (order level), and Lactobacillales (order level) decreased in the ICS group. However, the abundance of the above bacteria in each group of samples was Conclusions: Our results show that ICS and SCS have remarkably similar effects on the sputum microbiome of AECOPD patients.

Background and purposeAsthma has become the most common chronic respiratory disease in the world. Xiaoqinglong decoction (XQLD) is described as a commonly used drug for treatment and prevention of asthma for thousands of years, however, its underlying molecular mechanisms have not been clarified completely. Therefore, a network pharmacology and molecular docking technology were used to uncover the active compounds and pharmacological mechanism of XQLD on asthma.MethodsBioactive ingredients and targets of XQLD, asthma-related targets were obtained from public databases. Cytoscape software was used to construct biological networks. DAVID database was used to perform Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was performed to further verify the internal relationship between the active ingredients and key targets.ResultsA total of 169 bioactive ingredients and 127 gene targets of XQLD were identified. The network analysis indicated that quercetin, kaempferol, stigmasterol, β-sitosterol, and luteolin may be candidate agents. The IL6, VEGFA, NFKBIA, ICAM1, VCAM1, PPARG, IRF1, CYP3A4, CYP1B1 and CYP1A1 could become potential drug targets. The KEGG suggested that PI3K-AKT, Estrogen, FoxO, MAPK, HIF-1 signaling pathway may play a significant role in treating asthma. Molecular docking showed that quercetin, kaempferol, stigmasterol, β-sitosterol, and luteolin combined well with IL6, VEGFA, PPARG, CYP3A4.ConclusionThis study predicted the main ingredients, potential drug targets and pharmacological mechanism of XQLD on asthma from a new sight, as well as provided a promising approach for the research of chemical basis and pharmacology in Traditional Chinese medicine (TCM).

Introduction: Diffuse pulmonary lymphangiomatosis (DPL) is a rare condition. Most patients with DPL present dyspnea, cough, expectoration, and hemoptysis. There are few reports of DPL accompanied by thrombocytopenia, whose cause remains unknown. Patient concerns: An 18-year-old male patient presented with recurrent cough, expectoration, and dyspnea for 5 years, and thrombocytopenia was observed during a 2-month follow-up. Diagnosis: Chest computed tomography showed diffuse patchy shadows in both lungs, and pleural and pericardial effusions. Immunohistochemical lung tissue staining showed lymphatic and vascular endothelial cells positive for D2-40, CD31 and CD34. Routine blood test revealed platelets at 62 × 109 cells/L during follow-up. Bone marrow biopsy was normal. Ultrasound revealed no hepatosplenomegaly. Finally, the patient was diagnosed with DPL accompanied by thrombocytopenia. Interventions: He was treated by subtotal pericardial resection, thoracocentesis, and anti-infective therapy. Oral prednisone was administered for 2 months. Outcomes: The symptoms of cough and shortness of breath were improved, but thrombocytopenia persisted. We investigated the cause of thrombocytopenia. Whole-exome sequencing identified a mutation in exon 3 of the TNFRSF13B gene in this patient. Conclusion: DPL may present with thrombocytopenia and DIC. Patients with thrombocytopenia but not DIC and splenomegaly should be screened for gene mutations.

Asthma is a serious immune-mediated respiratory airway disease. Its pathological processes involve genetics and the environment, but it remains unclear. To understand the risk factors of asthma, we combined genome-wide association study (GWAS) risk loci and clinical data in predicting asthma using machine-learning approaches. A case–control study with 123 asthma patients and 100 healthy controls was conducted in Zhuang population in Guangxi. GWAS risk loci were detected using polymerase chain reaction, and clinical data were collected. Machine-learning approaches (e.g., extreme gradient boosting [XGBoost], decision tree, support vector machine, and random forest algorithms) were used to identify the major factors that contributed to asthma. A total of 14 GWAS risk loci with clinical data were analyzed on the basis of 10 times of 10-fold cross-validation for all machine-learning models. Using GWAS risk loci or clinical data, the best performances were area under the curve (AUC) values of 64.3% and 71.4%, respectively. Combining GWAS risk loci and clinical data, the XGBoost established the best model with an AUC of 79.7%, indicating that the combination of genetics and clinical data can enable improved performance. We then sorted the importance of features and found that the top six risk factors for predicting asthma were rs3117098, rs7775228, family history, rs2305480, rs4833095, and body mass index. Asthma-prediction models based on GWAS risk loci and clinical data can accurately predict asthma and thus provide insights into the disease pathogenesis of asthma. Further research is required to evaluate more genetic markers and clinical data and predict asthma risk.

Background: SARS-CoV-2 infects humans and has caused a global outbreak The main epidemic prevention measure is to isolate the source of infection An in-depth

Phenols are industrially generated intermediate chemicals found in wastewaters that are considered a class of environmental priority pollutants. Up-flow anaerobic sludge blanket (UASB) reactors are used for phenolic wastewater treatment and exhibit high volume loading capability, favorable granule settling, and tolerance to impact loads. Use of support materials can promote biological productivity and accelerate start-up period of UASB. In the present study, turf soil was used as a support material in a mesophilic UASB reactor for the removal of phenols in wastewater. During sludge acclimatization (45–96 days), COD and phenols in the treatments were both reduced by 97%, whereas these contents in the controls were decreased by 81% and 75%, respectively. The phenol load threshold for the turf soil UASB reactor was greater (1200 mg/L, the equivalent of COD 3000 mg/L) in comparison with the control UASB reactor (900 mg/L, the equivalent of COD 2250 mg/L) and the turf soil UASB reactor was also more resistant to shock loading. Improved sludge settling, shear resistance, and higher biological activity occurred with the turf soil UASB reactor due to the formation of large granular sludge (0.6 mm or larger) in higher relative percentages. Granular sludge size was further enhanced by the colonization of filamentous bacteria on the irregular surface of the turf soil.

Background Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome‐wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS‐supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. Methods A case‐control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). Results The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048‐3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001‐4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. Conclusion rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

The synthesis pathways of quorum sensing (QS) signal molecules and the mechanism of action of quorum sensing inhibitors (QSIs) have gained considerable attention as research topics in the field of food preservation. Here

Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 μg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 μmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 μmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 μg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.

Background Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection. Results We used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype. Conclusions The data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to provide novel ideas for prevention of P. marneffei-infection. Electronic supplementary material The online version of this article (doi:10.1186/s12866-017-1086-3) contains supplementary material, which is available to authorized users.

Objective IL‐1 receptor‐like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people. Methods We performed a case‐control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis. Results rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27‐3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47‐16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20‐6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39‐6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ. Conclusion rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.

Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40+ and CD86+ mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous fungal infection caused by certain dematiaceous fungi (usually Fonsecaea, Phialophora, or Cladophialophora). Histologically, CBM is characterized by the presence of medlar bodies. However, the diagnosis is difficult because of the rarity of these pathognomonic presentations and the wide variety of presentations. Treatment of these infections is challenging as it lacks standardization. Herein, we report a case of chromoblastomycosis caused by Phialophora, in a 42-year-old immunocompetent male agriculturist from the humid and subtropical region of southern China. He had a 3-month history of pneumonia with intermittent fever, coughing, and expectoration. The infection subsequently spread to the bone and lymph nodes forming deep lesions and eventually resulting in osteolysis and lymphadenectasis. These subcutaneous nodules were observed after 9 months. Antifungal treatment was administered for 20 months leading to clinical improvement before the patient was lost to follow-up. This case is unique because such deep lesions are rare in immunocompetent individuals and because the initial onset was associated with pneumonia.

Dendritic cells and CD8+ T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40−/− mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40−/− dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40−/−) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40−/− mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40−/− cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

Supplemental Digital Content is available in the text, Introduction: Anti–interferon-gamma (anti–IFN-γ) autoantibody increases susceptibility to lower-virulence pathogens and causes immunodeficiency syndrome in HIV–negative patients. Patient concerns: A 69-year-old Chinese man presented with a 2-month history of pruritic skin lesions on his forearms, trunk, and legs. He was diagnosed with 5 opportunistic infections without conventional immunosuppression-associated factors in past. The most conspicuous characteristics were recurrent pulmonary infection, persistent immunoglobulin E elevation and eosinophilia during the whole disease course. Diagnosis: Enzyme-linked immunosorbent assay showed anti–IFN-γ autoantibody positive. The final diagnosis for the patient was adult-onset immunodeficiency due to anti–IFN-γ autoantibody, non-tuberculous mycobacterial (NTM) infection and reactive dermatosis. Interventions: The patient underwent long-term anti-NTM and corticosteroid maintenance treatment. Outcomes: The patient was followed for 2 years during which opportunistic infection no longer happened, the immunoglobulin E level and eosinophil count reduced, the autoantibody levels remained largely steady and lung lesions absorbed. Conclusion: Clinicians should be vigilant for NTM infection in patients with anti–IFN-γ autoantibodies, even when culture results are negative. Long-term anti–non-tuberculous mycobacteria and glucocorticoid regimens were effective.

The application of aerobic granular sludge (AGS) is a promising biological method for wastewater treatment. In the present study, the AGS method was used for the treatment of petroleum wastewater. The granulation process and organic/nitrogen compound removal efficiencies were determined and correlated with the microbiological communities. Granulation of the aerobic sludge occurred after 35 days of operation. The compacted granules had a diameter of 0.46–0.9 mm. Extracellular polymeric substances (EPS) contents increased as granulation progressed and reached 128 mg/g·VSS. The granulated sludge efficiently reduced COD by 95% and petroleum compound contents by 90%. NH4+-N and TN removal were inefficient due to the inhibition of nitrobacteria and denitrificans, but were significantly improved by the addition of glucose. The microorganisms in the granules capable of degrading petroleum chemicals consisted of the genera Propioniciclava, Micropruina, Alphaproteobacteria, Flavobacterium, and Sulfuritalea.

Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 μg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.

Background Corticosteroids have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, whether inhaled corticosteroids (IC) alone have similar effects with systemic corticosteroid (SCS) is still unclear. Objectives To compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AECOPD. Methods 30 AECOPD patients were randomly divided into two group. Budesonide group (15 cases) were treated with inhaled budesonide (3 mg Bid); methylprednisolone group (15 cases) were treated with systemic methylprednisolone (methylprednisolone acetate injectable suspension 40 mg Qd for three days and then methylprednisolone tablets 8 mg Bid). Observe symptoms, lung function, blood gas analysis and adverse effects of the patients in two groups. Peripheral blood samples were collected before and after treatment for 1 day, 4 days and 7 days. Interleukin-8 (IL-8) and TNF-α levels were determined by an enzyme linked immunosorbent assay (ELISA). Hs-CRP levels were detected by automatic biochemical analyzer. Western blotting was used to determine histone deacetylase 2 (HDAC2) protein expression. Measurements and main results Symptoms, pulmonary function and blood gas analysis were significantly improved after treatment in the two groups (P 0.05). There were no significant differences of IL-8, TNF-α and hs-CRP levels in the two groups (P > 0.05). Besides, the levels of HDAC2 protein expression before treatment were significantly lower comparing to that after treatment for 4 and 7 days. Incidence of adverse events (heart rate, blood pressure, glycemic , sleep condition, gastrointestinal symptoms) in budesonide group was lower than methylprednisolone group ( P Conclusions Inhaled budesonide and systemic methylprednisolone have the same effects on systemic inflammation of AECOPD. Inhaled corticosteroid alone could instead systemic corticosteroid in AECOPD treatment.

Castleman disease (CD) is a rare reactive lymphoproliferative disorder, first identified in 1954. We recently had the opportunity to analyse the characteristics of two variations of CD with pulmonary involvement. Case 1 had localised retroperitoneal hyaline vascular type CD, while Case 2 was diagnosed as multicentric plasma cell type CD. Both patients had pulmonary symptoms and signs, including cough, dyspnoea, hypoxaemia and ventilatory dysfunction; however, they had different physiological manifestations of their pulmonary abnormalities.

Title of data- Sequences of P. marneffei strains using PCR and the sequence of PCR product. Description of data- The GXHCBR P. marneffei strains were identified by gold standard DNA sequencing of the fungal ITS region using PCR and the sequence of PCR product. (DOCX 12 kb)

Title of data-raw data. Description of data- The raw data of Fig. 4, Fig. 5 and Fig. 6, please see Tables 1, 2, and 3, respectively. (DOCX 27 kb)

Background Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. Objectives To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. Methods The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. Results NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. Conclusions NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.

Histone deacetylases (HDACs) are families of enzymes that regulate chromatin structure and thus affect inflammatory gene expression. The anti-inflammatory properties of macrolides are well documented. However, the effects of macrolides on HDAC protein expression have not been studied. This study aimed to examine the molecular mechanism of the inflammatory responses caused by cigarette smoke extract (CSE) and the effects of erythromycin (EM) on CSE-induced HDAC protein expression in human macrophages in vitro. The cells were preincubated with EM and were then exposed to CSE. Levels of interleukin-8 (IL-8) and tumor necrosis factor-a (TNF-a) were assayed by enzyme linked immunosorbent assay (ELISA). Nuclear factor-κB (NF-κB) activity was assessed by an electrophoretic mobility shift assay. HDAC activity was measured with a colorimetric assay kit, and Western blotting was used for HDAC1, -2, -3 and NF-κB protein expression assays. The results showed that CSE causes decreases in HDAC activity and HDAC1, -2, -3 levels and upregulates NF-κB activity, resulting in increased NF-κB-dependent proinflammatory cytokine release in human macrophage cells. Moreover, EM was able to reverse the CSE-induced decline in HDAC1, -2, -3 protein expression, which was most prominent for HDAC2; these changes were associated with the suppression of both NF-κB protein expression and the production of inflammatory mediators. These results suggest that relieving inflammation with EM can be useful in therapeutic approaches for modulating intracellular nuclear signaling in chronic airway inflammatory diseases such as chronic obstructive pulmonary disease (COPD).

Heavy smoking can induce airway inflammation and emphysema. Macrolides can modulate inflammation and effector T-cell response in the lungs. However, there is no information on whether erythromycin can modulate regulatory T-cell (Treg) response. This study is aimed at examining the impact of erythromycin on Treg response in the lungs in a rat model of smoking-induced emphysema. Male Wistar rats were exposed to normal air or cigarette smoking daily for 12 weeks and treated by gavage with 100 mg/kg of erythromycin or saline daily beginning at the forth week for nine weeks. The lung inflammation and the numbers of inflammatory infiltrates in bronchoalveolar lavage fluid (BALF) were characterized. The frequency, the number of Tregs, and the levels of Foxp3 expression in the lungs and IL-8, IL-35, and TNF-α in BALF were determined by flow cytometry, RT-PCR and ELISA, respectively. Treatment with erythromycin reduced smoking-induced inflammatory infiltrates, the levels of IL-8 and TNF-α in the BALF and lung damages but increased the numbers of CD4+Foxp3+Tregs and the levels of Foxp3 transcription in the lungs, accompanied by increased levels of IL-35 in the BALF of rats. Our novel data indicated that erythromycin enhanced Treg responses, associated with the inhibition of smoking-induced inflammation in the lungs of rats.

To analyze the clinical features of idiopathic sweet's syndrome (SS) that involves the lung.A retrospective analysis was carried out on clinical data of 3 cases of patients with idiopathic SS that involves the lung who were admitted in the First Affiliated Hospital of Guangxi Medical University from August 2012 to December 2013. And relevant literatures were reviewed.Among the literatures reported between 1981 and 2014, there were a total of 39 SS cases involving the lung from both home and abroad, where 31 cases were accompanied with other diseases (i.e. blood diseases); the rest 8 cases without comorbidities were diagnosed as idiopathic SS, which were included into the analysis plus the 3 cases of this group. Among 11 cases, 6 cases were male while 5 cases were female, with the average age of 47 years old (25-72 years old). The patients all had the symptoms of fever, cough and dyspnea; painful and red pseudo-blisters rashes, pulmonary rale, hypoxemia and pulmonary exudative shadow. 3 cases had swollen lymph nodes. Rashes appeared before lung involvement in 6 cases while after lung involvement in 5 cases. In 11 cases, white blood cells, neutrophils, ESR and CRP were all significantly increased. Pulmonary CT showed unilateral or bilateral pulmonary invasive exudates and consolidation with pleural reaction. 3 cases showed restrictive ventilatory dysfunction. BAF fluid (9/9 cases) was given priority to neutrophils. Pulmonary pathology (9/9 cases) showed neutrophils-infiltrating interstitial pneumonia or organizing pneumonia, which were in accordance with the rash pathology (11/11 cases). 11 cases all had been misdiagnosed as invalid antibiotic treatment on pneumonia; where 9 cases were healed by glucocorticoid while 2 cases died.Idiopathic SS involving the lung is rare in clinical, which can appear before or after rash. Idiopathic SS is often misdiagnosed as bacterial pneumonia. Clinical features include the unknown increase of mature neutrophils, fever, dyspnea, and even respiratory failure, lung exudative or consolidation shadows, swollen lymph nodes and red and painful pseudo-blisters rashes. The involved area is often infiltrated by numerous neutrophils. The glucocorticoid has special effects, but easy to relapse, can also cause death.

SummaryPenicillium marneffei is a thermally dimorphic pathogenic fungus that causes systemic infection similar to disseminated cryptococcosis. P. marneffei is endemic in Southeast Asia, usually infecting HIV-infected individuals; infection of HIV-negative individuals is extremely rare. Here, we describe a disseminated P. marneffei infection within an osteolytic lesion in an HIV-negative patient. A 40-year-old Chinese woman presented with intermittent fever, generalized lymphadenopathy, and a skin rash. Following a sternum biopsy, the patient was diagnosed with P. marneffei infection. An emission computed tomography bone scan revealed the presence of increased radioactivity in the left clavicle and sternum, indicative of an osteolytic lesion. In addition to reporting this very rare case, we also present a brief review of the literature, highlighting the differences in clinical manifestations between HIV-positive and HIV-negative patients infected with P. marneffei as it applies to our case.

Background Penicillium marneffei disseminates hematogenously and can infect most organs, though infection leading to osteolysis is extremely rare. We describe the clinical and laboratory features, management, and outcomes of patients with penicilliosis marneffei (PSM) with osteolytic lesions. Methods This retrospective study was conducted between January 1, 2003 and May 1, 2014 at the First Affiliated Hospital of Guangxi Medical University. Patients who presented with culture and/or histopathologic proof of disseminated PSM within osteolytic lesions were included. Results P. marneffei infection was diagnosed in 100 patients (65 HIV-infected and 35 HIV-negative). Fourteen patients, all HIV-negative, (14/35, 40%) had osteolytic lesions. The most common comorbidity was diabetes mellitus, though previous glucocorticoid therapy, β-thalassemia, breast cancer, and Langerhans cell histiocytosis also occurred. Five patients had no comorbidity. Fever, malaise, ostealgia, weight loss, and anemia were the most common symptoms, followed by cutaneous lesions, lymphadenopathy, hepatosplenomegaly, cough, sputum, and stethalgia. Ostealgia, joint pain, and joint disorders were also recorded. White blood cell and neutrophil counts were increased (mean 22.3 ± 7.4 × 109 cells/L; mean 18.84 ± 4.5 × 109 cells/L, respectively). The most common sites were the vertebrae, skull and femur, ribs and ilium, though the clavicle, scapula, humerus, and tibia were also involved. Radiography and computed tomography (CT) showed multiple radiolucencies with moth-eaten bone destruction, periosteal proliferation, bone fracture, and surrounding soft-tissue swelling. Emission CT showed significantly increased uptake in many skeletal regions. Positron emission tomography/CT showed generalized lymphadenopathy, bone metabolic activity, and bone destruction. The 18 F-FDG standard uptake value was increased in the entire skeleton (mean 6.16). Twelve patients received antifungal therapy, four of whom died during treatment, and eight recovered, though four of these eight relapsed within 3–24 months. Two patients discontinued treatment because of severe multiple organ failure and died. Conclusions Osteolysis is often overlooked in HIV-negative individuals with disseminated P. marneffei infection. However, P. marneffei involving the bone and leading to osteolysis may indicate severe systemic disturbance, and is characterized by a poor prognosis, high recurrence rate, and the need for prolonged antifungal treatment.

Background Penicillium marneffei is the only dimorphic member of the genus and is an emerging pathogenic fungus that can cause fatal systemic mycosis. Penicillium marneffei disseminates hematogenously to other locations. Penicillium marneffei infection most commonly involves the skin, lungs, and reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported. Infection involving the trachea has not been previously reported. Case presentation We herein report a previously healthy 28-year-old male farmer from Guangxi Province without HIV who became infected with P. marneffei. The infection primarily affected the trachea, resulting in structural damage to the cartilage, tracheal stenosis, and tracheal absence. The infection also involved the lungs and lymph nodes. After antifungal treatment and surgery, his symptoms, signs, and lung imaging findings showed significant improvement. This is the first such case report. Conclusion Penicillium marneffei infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. Penicillium marneffei hematogenously disseminates throughout the whole body. This is the first reported case of P. marneffei infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence.