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HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. We analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, we found that the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential in vitro. In vivo, HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation. These data indicate that HOXA6 promotes cell proliferation, migration, and invasion and that the HOXA6-PBX2 axis may be a useful biomarker for disease progression in GC.

Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-β1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-β1-induced IMR-90 cells. Moreover, the combination of PLB with/without TβRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-β1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-β1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-β1-induced IMR-90 cells, and suppressed TGF-β1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-β1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS., Graphical abstract, GRAPHICAL ABSTRACT

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.

Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 μg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.

In human gastric cancer (GC), the upregulation of FOXK1 and vimentin is frequently observed in cancer cells and correlates with increased malignancy. We report that FOXK1 synergizes with vimentin to promote GC invasion and metastasis via the induction of epithelial-mesenchymal transition (EMT). We showed that higher expression levels of FOXK1 were significantly associated with GC development. FOXK1 can physically interact with and stabilize vimentin. Moreover, a positive correlation between the expression of FOXK1 and vimentin was found in GC cells. Higher expression levels of these two proteins were significantly associated with differentiation, lymph node metastasis, AJCC stage, and poorer prognosis. Furthermore, the coexpression of FOXK1 and vimentin enhances cell metastasis through the induction of EMT in GC cells. However, the siRNA-mediated repression of vimentin in FOXK1-overexpressing cells reversed the EMT-like phenotype and reduced GC cell migration and invasion in vitro and in vivo. Altogether, our findings suggest that the vimentin-FOXK1 axis provides new insights into the molecular mechanisms underlying EMT regulation during GC progression and metastasis.

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 Lung adenocarcinoma is characterized by early asymptomatic progression and metastasis. Appearance of respiratory symptoms usually means the disease is aggravated. The aim of this study was to identify the protein profile in plasma of lung adenocarcinoma of stages I-IV, and look for novel diagnostic biomarkers. Methods Isobaric tags for relative and absolute quantification (iTRAQ) coupled with two dimensional liquid chromatography - tandem mass spectrometry technology (2D LC-MS/MS) was applied to separate and identify differential expression of proteins in plasma specimens from 10 healthy individuals, 10 patients with pneumonia, 7 patients with lung adenocarcinoma of stages I-II, respectively, and 10 patients with lung adenocarcinoma of stages III-IV, then analyze the functions of the differential expression of proteins by bioinformatics. Results ADAMTS-like protein 4, Fibrinogen-like protein 1 precursor, secretoglobin family 3A member 2 and haptoglobin were up-regulated in patients with lung adenocarcinoma by proteomics analysis, and the expression levels of SCGB3A2 and Hp by ELISA were consistent. Pathway analysis of identified differential expression of proteins showed they were mainly involved in chemokine/p53/TGF-beta signaling pathway. Conclusions Plasma SCGB3A2 is a potential maker for diagnosis of primary pulmonary adenocarcinoma. Abnormal post-translational protein modification may be associated with the progression of lung cancer.

Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD. Previous studies have demonstrated the anti-inflammatory effects of macrolides. However, the effects of macrolides on the cigarette smoke extract- (CSE-) induced immune response are unclear. Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE-exposed DCs polarizing naïve CD4+ T cells into Th17 cells. DCs were generated from bone marrow-derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE-exposed DC group, CD40-antibody-blocked CSE-exposed DC group, and EM-treated CSE-exposed DC group. The function of polarizing CD4+ T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4+ T cells. CD40 expression in DCs in the CSE-exposed group increased significantly compared with that in the control group (P < 0.05). The Th17 cells in the CSE-exposed DC/MLR group increased significantly compared with those in the control DC/MLR group (P < 0.05). Moreover, Th17 cells in the CD40-blocked CSE-exposed DC/MLR group and EM-treated CSE-exposed DC/MLR group were reduced compared with those in the CSE-exposed DC/MLR group (P < 0.05). Thus, these findings suggested that EM suppressed the CSE-exposed DC-mediated polarization of CD4+ T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway.

Background: The transcription factor HOXD9 is one of the members of the HOX family, which plays an important role in neoplastic processes. However, the role of HOXD9 in the growth and metastasis of gastric cancer (GC) remains to be elucidated. Methods: In vitro functional role of HOXD9 and RURY3 in GC cells was determined using the TMA-based immunohistochemistry, western blot, EdU incorporation, gelatin zymography, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. In vivo tumour growth and metastasis were conducted in nude mice. Findings: HOXD9 is overexpressed in GC cells and tissues. The high expression of HOXD9 was correlated with poor survival in GC patients. Functionally, HOXD9 expression significantly promoted the proliferation, invasion and migration of GC cells. Mechanically, HOXD9 directly associated with the RUFY3 promoter to increase the transcriptional activity of RUFY3. Inhibition of RUFY3 attenuated the proliferation, migration and invasiveness of HOXD9-overexpressing GC cells in vitro and in vivo. Moreover, both HOXD9 and RUFY3 were highly expressed in cancer cells but not in normal gastric tissues, with their expressions being positively correlated. Interpretation: The evidence presented here suggests that the HOXD9-RUFY3 axis promotes the development and progression of human GC. Funding Statement: This study was supported by grants from the National Natural Science Funds of China (Nos.81672875 and 81772964). The funding organization: the Guangzhou Pilot Project of the Clinical and Translational Research Center (early gastrointestinal cancer, No.7415696196402). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was reviewed and approved by the Medical Ethics Committee of Nanfang Hospital (NFEC-2017-062), Southern Medical University, Guangzhou, China. All animal studies were approved by the Institutional Animal Care and Use Committee of Committee of Nanfang Hospital.

Aims This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis. Main methods The expression and activity of fibrotic factors [interleukin (IL)-6, IL-8, autophagy related 5 (ATG5), collagen (COL)-1, tumor growth factor (TGF)-β COL-3, microtubule-associated proteins 1A/1B light chain 3A (LC3), and vascular endothelial growth factor (VEGF)] and fibrotic signaling mediators [mammalian target of rapamycin (mTOR) and phosphorylated AKT (pAKT)] were detected by real-time quantitative PCR (qRT-PCR), ELISA, Western blot, and immunohistochemical staining, respectively, in the lipopolysaccharide (LPS)-induced WI-38 (a human embryonic lung fibroblast cell line) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model, with and without quercetin treatment. Key findings Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors (IL-6, IL-8, COL-1, COL-3, LC3) and fibrotic signaling mediators (mTOR and AKT), and it induced the downregulation of ATG5 in the WI-38 cells. Furthermore, the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model. Thus, the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model, in addition to effectively reversing an increase in pro-fibrotic factors (VEGF, IL-6, TGF-β, COL-1, and COL-3) and fibrotic signaling mediators (mTOR and AKT), as well as downregulating ATG5 of the rabbit tracheal stenosis model. Significance Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling pathway, in addition to activating autophagy activity. This study provided experimental evidence supporting the application of quercetin in tracheal stenosis, clinically.

Background: A limitation of bronchoscopic balloon dilatation (BBD) is that airflow must be completely blocked for as long as possible during the operation. However, the patient often cannot hold his or her breath for a long period affecting the efficacy of the procedure. In this study, we used an extra-small-diameter tube to provide assisted ventilation to patients undergoing BBD and assessed the efficacy and safety of this technique. Methods: Bronchoscopic balloon dilatation was performed in 26 patients with benign tracheal stenosis using an extra-small-diameter tube. The tracheal diameter, dyspnea index, blood gas analysis results, and complications were evaluated before and after BBD. Statistical analyses were performed by SPSS version 16.0 for Windows (SPSS, Inc., Chicago, IL, USA). Results: Sixty-three BBD procedures were performed in 26 patients. Dyspnea immediately improved in all patients after BBD. The tracheal diameter significantly increased from 5.5 ± 1.5 mm to 13.0 ± 1.3 mm (P < 0.001), and the dyspnea index significantly decreased from 3.4 ± 0.8 to 0.5 ± 0.6 (P < 0.001). There was no significant change in the partial pressure of oxygen during the operation (before, 102.5 ± 27.5 mmHg; during, 96.9 ± 30.4 mmHg; and after, 97.2 ± 21.5 mmHg; P = 0.364), but there was slight temporary retention of carbon dioxide during the operation (before, 43.5 ± 4.2 mmHg; during, 49.4 ± 6.8 mmHg; and after, 40.1 ± 3.9 mmHg; P < 0.001). Conclusion: Small-diameter tube-assisted BBD is an effective and safe method for the management of benign tracheal stenosis.

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.

1.Talaromyces marneffei, formerly known as Penicillium marneffei, usually affects the monocyte-macrophage system and can cause fatal systemic mycosis in immunocompromised individuals. This retrospective study is the first to describe the clinical and endoscopic (nasal endoscopy, flexible endoscopy) features of penicilliosis with pharynx and/or larynx infection in patients with acquired immunodeficiency syndrome (AIDS). 2.During the study period, 126 patients were diagnosed with penicilliosis. Among them, only seven who presented with culture and/or histopathological evidence of pharyngeal and/or laryngeal T. marneffei infection were included; notably, all of these patients also had AIDS. 3.The most common specific pharyngeal and laryngeal features were sore throat, hoarseness, dysphagia, a pharyngeal and laryngeal mass and/or mucosal ulcerations, and enlargement of multiple cervical and axillary lymph nodes. Evaluation using nasal endoscopy and flexible endoscopy revealed pharyngeal and laryngeal ulcers and/or a mass. 4.Histopathological analysis of all pharyngeal and/or laryngeal tissue samples in our retrospective study revealed positivity for T. marneffei. The most common pathological type was non-reactive necrosis. 5.Histopathology and fungal culture of pharyngeal and laryngeal secretions and tissues are important and safe methods that allow determination of an accurate etiological basis for penicilliosis with pharyngeal and/or laryngeal infection, as well as differentiation from other diseases such as tuberculosis, lymphoma, pharyngeal cancer, and Kaposi's sarcoma. This article is protected by copyright. All rights reserved.

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.

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.

Infection with Penicillium marneffei has rarely been reported in human immunodeficiency virus (HIV)-negative infants. We aimed to determine the epidemiological, clinical, pathological, and immunological characteristics of 7 HIV-negative infants infected by P. marneffei, and to provide insights into its diagnosis and treatment. We retrospectively reviewed the cases of 7 HIV-negative infants infected by P. marneffei who presented to the First Affiliated Hospital of Guangxi Medical University between January 1, 2003 and December 1, 2014. The infants’ median age was 23.43 months (SD = 8.34), and all lived in Guangxi Province in China, where P. marneffei is endemic. The median time from disease onset to diagnosis was 2.29 months (SD = 2.12). Of the cases studied, 5 (71.43%) had medical histories that included frequent pneumonia or bronchopneumonia, thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia, followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four patients had slightly elevated white blood cell counts. The lymphocyte and CD4+ T-cell counts were normal. The CD8+ T-cell counts, serum immunoglobulin (Ig) G titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes were affected. One case who received intravenous amphotericin B and 3 cases who received intravenous voriconazole improved, and these patients were cured after continual treatment with oral voriconazole for 6 or 12 months. The remaining patients died before they received antifungal treatment. P. marneffei causes severe disease and disseminated infections, and it has high mortality rates in HIV-negative infants in endemic areas. P. marneffei susceptibility may be associated with immunodeficiencies or immune disorders. In endemic areas, clinicians should aware of disseminated P. marneffei infections when infants present with serious or recurrent infections, even if they are HIV negative. P. marneffei is highly susceptible to amphotericin B and voriconazole. Timely diagnosis and treatment can improve patients’ prognoses. Intravenous voriconazole could be recommended as the initial antifungal agent for HIV-negative infants infected by P. marneffei, because of its low nephrotoxicity, high sensitivity, and high efficacy levels.

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.

The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

Talaromyces marneffei infection involving the trachea presents as diffuse irregular nodules that grow on the tracheal lumen and/or rarely present as concurrent severe eosinophilia. Herein, we report two patients without HIV infection whose main tracheal and/or principal bronchi were involved by T. marneffei infection, which manifested as diffuse proliferative nodules. In case 1, the infection primarily affected the main trachea, resulting in structural cartilage damage, tracheal stenosis, and tracheal absence. In case 2, there were diffuse proliferative nodules in the trachea and bronchi with marked eosinophilia. The final diagnosis was made based on a positive culture from bronchiolar lavage fluid, skin, and tracheal polyps. Case 1 was administered antifungal treatment combined with surgery, but relapse occurred during a 3-month follow-up period. Case 2 was treated by intravenous liposomal amphotericin B combined with atomized inhaled liposomal amphotericin B, and he later showed improvement; there was no relapse during the 12-month period of antifungal treatment. Importantly, atomized inhaled amphotericin B antifungal treatment for T. marneffei infection has never been previously reported.

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.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and is associated with acute exacerbations. Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases. Objective: The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients. Methods: We conducted a randomized, placebo-controlled, double-blind trial of erythromycin for a period of 6 months. Thirty-six COPD patients were randomized to treatment with oral erythromycin (125 mg, three times/day) or placebo. The primary outcomes were neutrophil number in sputum and exacerbations. Results: Thirty-one patients completed the study. At the end of treatment, neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients (p = 0.005). Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group (p = 0.021 and p = 0.024, respectively). The mean exacerbation rate was lower in the erythromycin group than in the placebo group (relative risk = 0.554, p = 0.042). Kaplan-Meier survival analysis showed that erythromycin significantly delayed the time to the first COPD exacerbation compared with placebo (p = 0.032). Conclusions: Erythromycin treatment in COPD patients can reduce airway inflammation and decrease exacerbations and may therefore be useful in the management of COPD.

The aim of this study was to investigate the presence of epithelial neutrophil-activating peptide (ENA)-78 in pleural effusions, as well as the chemoattractant activity of pleural ENA-78 on neutrophils. Pleural effusion and serum samples were collected from 75 patients who presented to the respiratory institute (19 with malignant pleural effusion, 21 with tuberculous pleural effusion, 18 with infectious pleural effusion and 17 with transudative pleural effusion). The concentrations of ENA-78, myeloperoxidase and neutrophil elastase were determined, and the chemoattractant activity of ENA-78 for neutrophils both in vitro and in vivo was also observed. The concentrations of ENA-78, myeloperoxidase and neutrophil elastase in infectious pleural effusion were significantly higher than those in malignant, tuberculous and transudative groups, respectively (all p0.01). Infectious pleural fluid was chemotactic for neutrophils in vitro and anti-ENA-78 antibody could partly inhibit these chemotactic effects. Intrapleural administration of ENA-78 produced a marked progressive influx of neutrophils into pleural space. Compared with noninfectious pleural effusion, ENA-78 appeared to be increased in infectious pleural effusion. Our data suggested that ENA-78 was able to induce neutrophil infiltration into pleural space and might be responsible for pleural neutrophil degranulation.