An unusual case of abdominal pain: psychogenic vomiting complicated by spontaneous pneumomediastinum.

BACKGROUND: Spontaneous pneumomediastinum (SPM) was defined by the appearance of free air in the mediastinum that was not preceded by trauma, surgery, or other medical procedures. Among the numerous manifestations of SPM, abdominal pain had seldom been described. CASE PRESENTATION: A 25-year-old man presented to the emergency department with nausea, vomiting, and abdominal pain for 7 days. The presenting clinical features and the radiological results were suggestive of psychogenic vomiting with spontaneous pneumomediastinum in a patient who suffered from abdominal pain. CONCLUSIONS: The special feature of this case was the elucidation of a rare cause of abdominal pain, which should be differentiated in patients with vomiting combined with abdominal pain. The importance of this case was that its recognition may prevent unnecessary procedures to rule out or treat other causes of abdominal pain.

Clinical significance of serum levels of 14-3-3ß protein in patients with stable chronic obstructive pulmonary disease.

Nowadays, the diagnosis and treatment of COPD are often based on the results of lung function tests. Certain individuals, however, are not candidates for lung function testing due to pulmonary bullae, cardiac failure, low lung function, and other factors. Therefore, we evaluated whether serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein ß (14-3-3ß) could be a biomarker for the diagnosis of stable COPD patients. The expression of serum 14-3-3ß protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3ß protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P < 0.001). Furthermore, serum 14-3-3ß protein concentrations were higher in GOLD 3&4 COPD patients compared with healthy participants, GOLD 1 and GOLD 2 COPD patients (P < 0.05), which shows that the concentration of 14-3-3ß protein correlates with disease severity in stable COPD patients. After 1:1 PSM, there was also a statistically significant rise in 14-3-3 protein levels in stable COPD patients compared to healthy controls (P < 0.01). Serum 14-3-3ß protein levels were positively correlated with blood neutrophil levels (P < 0.05), and negatively related to lung function parameters in stable COPD patients (P < 0.01). When the cutoff value was set at 29.53 ng/ml, the ROC curve yielded a sensitivity of 84.9% and a specificity of 68.3% for diagnosing stable COPD. The 14-3-3ß protein may be a potential serum biomarker for the diagnosis of stable COPD patients, which is associated with disease severity, systemic inflammation, and small airway obstruction.

Serum 14-3-3ß protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study.

BACKGROUND: The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein ß (14-3-3ß) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3ß in asthmatic patients. METHODS: We recruited 54 asthmatic patients with acute exacerbation and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals. Clinical characteristics, clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC% predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and serum 14-3-3ß levels were measured to compare among each group. Spearman's rank correlation coefficient was used to evaluate the correlation between 14-3-3ß and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3ß. RESULTS: Our results showed that median (interquartile range) of serum 14-3-3ß concentration (ng/mL) in acute exacerbation group of asthma (41.18 [33.06-51.76]) was much higher than that in normal control group (24.99 [17.43-29.91]; P < 0.001) and chronic persistent group of asthma (25.88 [21.03-34.55]; P < 0.001). Spearman's correlation coefficient shows that the serum 14-3-3ß level was positively correlated with FeNO (r = - 0.292, P = 0.032) and peripheral blood eosinophil count (r = 0.328, P = 0.016), and was negatively related to FEV1/FVC (r = - 0.293, P = 0.031) in the acute exacerbation group of asthma. At the same time, the serum 14-3-3ß level was also negatively associated with FEV1 (r = - 0.297, P = 0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute exacerbation group of asthma with normal control group demonstrated a significant (P < 0.001) AUC of 0.90 (95% CI 0.85-0.96). CONCLUSION: The serum 14-3-3ß protein may become a potential biomarker in asthmatic patients with acute exacerbation.

Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway.

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidium monnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program.

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.

IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages.

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has one of the poorest prognosis. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined that IL-24, an IL-20 subfamily cytokine member, was increased both in the serum of IPF patients and the bronchoalveolar lavage fluid (BALF) of mice following bleomycin (BLM)-induced pulmonary fibrosis. As a result, IL-24 deficiency protected mice from BLM-induced lung injury and fibrosis. Specifically, loss of IL-24 significantly attenuated transforming growth factor ß1 (TGF-ß1) production and reduced M2 macrophage infiltration in the lung of BLM-induced mice. Mechanistically, IL-24 alone did not show a perceptible impact on the induction of M2 macrophages, but it synergized with IL-4 to promote M2 program in macrophages. IL-24 suppressed IL-4-induced expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, through which it enhanced signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma (STAT6/PPARγ) signaling, thereby promoting IL-4-induced production of M2 macrophages. Collectively, our data support that IL-24 synergizes with IL-4 to promote macrophage M2 program contributing to the development of pulmonary fibrosis.

The Role of Macrophage Migration Inhibitory Factor (MIF) in Asthmatic Airway Remodeling.

PURPOSE: Recent studies have demonstrated that macrophage migration inhibitory factor (MIF) is of importance in asthmatic inflammation. The role of MIF in modulating airway remodeling has not yet been thoroughly elucidated to date. In the present study, we hypothesized that MIF promoted airway remodeling by intensifying airway smooth muscle cell (ASMC) autophagy and explored the specific mechanisms. METHODS: MIF knockdown in the lung tissues of C57BL/6 mice was conducted by instilling intratracheally adeno-associated virus (AAV) vectors (MIF-mutant AAV9) into mouse lung tissues. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/-) was used to detect the role of autophagy in ovalbumin (OVA)-asthmatic murine models. Moreover, to block the expression of MIF and CD74 in vitro models, inhibitors, antibodies and lentivirus transfection techniques were employed. RESULTS: First, MIF knockdown in the lung tissues of mice showed markedly reduced airway remodeling in OVA murine mice models. Secondly, ASMC autophagy was increased in the OVA-challenged models. Mice genetically deficient in the autophagy marker ATG5 (ATG5+/-) that were primed and challenged with OVA showed lower airway remodeling than genetically wild-type asthmatic mice. Thirdly, MIF can induce ASMC autophagy in vitro. Moreover, the cellular source of MIF which promoted ASMC autophagy was macrophages. Finally, MIF promoted ASMC autophagy in a CD74-dependent manner. CONCLUSIONS: MIF can increase asthmatic airway remodeling by enhancing ASMC autophagy. Macrophage-derived MIF can promote ASMC autophagy by targeting CD74.

Diagnostic accuracy of 14-3-3 η protein in rheumatoid arthritis: A meta-analysis.

AIM: To evaluate the overall diagnostic performance of 14-3-3 η protein in patients with rheumatoid arthritis (RA). METHODS: PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published in English before 20 February 2020 were included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of 14-3-3 η protein for RA was conducted by using a random effects model. Subgroup analysis was used to explore the sources of heterogeneity. Deeks' funnel plot asymmetry test was used to evaluate for the presence of publication bias. RESULTS: A total of 13 studies (1554 positive and 1934 negative participants) were included. The pooled sensitivity and specificity were 0.73 (95% CI 0.71-0.75) and 0.88 (95% CI 0.87-0.90), respectively. The pooled positive/negative likelihood were 5.98 (95% CI 4.39-8.14) and 0.28 (95% CI 0.21-0.37), respectively. In addition, the pooled diagnostic odds ratio was 23.48 (95% CI 13.76-40.08) and the area under curve was 0.9245. The results of subgroup analysis indicated that ethnicity and control group might be the source of heterogeneity. The results of sensitivity analysis were stable. No significant publication bias was found. CONCLUSIONS: The current evidence indicated that 14-3-3 η protein has moderate accuracy for the diagnosis of RA.

Blockade of JAK2 protects mice against hypoxia-induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation.

OBJECTIVES: Hypoxia is an important risk factor for pulmonary arterial remodelling in pulmonary arterial hypertension (PAH), and the Janus kinase 2 (JAK2) is believed to be involved in this process. In the present report, we aimed to investigate the role of JAK2 in vascular smooth muscle cells during the course of PAH. METHODS: Smooth muscle cell (SMC)-specific Jak2 deficient mice and their littermate controls were subjected to normobaric normoxic or hypoxic (10% O2 ) challenges for 28 days to monitor the development of PAH, respectively. To further elucidate the potential mechanisms whereby JAK2 influences pulmonary vascular remodelling, a selective JAK2 inhibitor was applied to pre-treat human pulmonary arterial smooth muscle cells (HPASMCs) for 1 hour followed by 24-hour hypoxic exposure. RESULTS: Mice with hypoxia-induced PAH were characterized by the altered JAK2/STAT3 activity in pulmonary artery smooth muscle cells. Therefore, induction of Jak2 deficiency in SMCs protected mice from hypoxia-induced increase of right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodelling. Particularly, loss of Jak2 significantly attenuated chronic hypoxia-induced PASMC proliferation in the lungs. Similarly, blockade of JAK2 by its inhibitor, TG-101348, suppressed hypoxia-induced human PASMC proliferation. Upon hypoxia-induced activation, JAK2 phosphorylated signal transducer and activator of transcription 3 (STAT3), which then bound to the CCNA2 promoter to transcribe cyclin A2 expression, thereby promoting PASMC proliferation. CONCLUSIONS: Our studies support that JAK2 could be a culprit contributing to the pulmonary vascular remodelling, and therefore, it could be a viable target for prevention and treatment of PAH in clinical settings.

E4BP4 facilitates glucocorticoid sensitivity of human bronchial epithelial cells via down-regulation of glucocorticoid receptor-beta.

It has recently been recognized that a subset of asthma patients suffer from glucocorticoid (GC) insensitivity, and glucocorticoid receptor-ß (GR-ß) is associated with corticosteroid resistance, but the underlying mechanisms remain unknown. Here we demonstrated that Interleukin-17A induced glucocorticoid sensitivity in human bronchial epithelial cells (16HBE) is enhanced, which is depend on E4 promoter-binding protein 4 (E4BP4) mediated GR-ß expression. Our data show that the expression of E4BP4 is significantly up-regulated in 16HBE cells, and the depletion of E4BP4 dramatically decreased glucocorticoid sensitivity in IL-17A induced 16HBE cells. Mechanistic studies revealed that E4BP4 plays a crucial role in Interleukin-17A induced glucocorticoid sensitivity in 16HBE cells via down-regulating GR-ß, which is probably mediated by PI3K/Akt activation. Collectively, we can draw the conclusion that E4BP4 contribute to enhance the GCs sensitivity, which may offer a new strategy for therapeutic intervention for GC-insensitive asthma.

Total alkaloids of Corydalis saxicola bunting inhibits migration of A549 cells by suppressing Cdc42 or Vav1.

Cell division cycle 42 (Cdc42) is a critical regulator, which functions in cancer metastasis. Numerous previous studies have demonstrated that vav guanine nucleotide exchange factor 1 (Vav1) is ectopically expressed in numerous types of human malignancies and have suggested that Vav1 may efficiently promote the formation of invadopodia and matrix degradation by regulating the activation of Cdc42. Total alkaloids of Corydalis saxicola bunting (TAOCSB), a type of alkaloid compound extracted from the root of C. saxicola bunting, has been revealed to have anticancer properties. However, there is no available information to address the effects of TAOCSB on the metastasis of human lung cancer. In the present study, the anticancer effect on A549 non-small cell lung cancer cells induced by TAOCSB was investigated, as well as its underlying mechanisms. The results demonstrated that a low dose of TAOCSB exhibited anti-metastatic potential in suppressing the invasion and migration of A549 cells, and this action may be involved in TAOCSB-mediated inhibition of Cdc42 expression at the level of mRNA and protein in parallel with TAOCSB-mediated inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 protein expression levels. Although the present study did not reveal the expression level of Vav1 protein in A549 cells, the expression level of Vav1 mRNA was investigated. The effect of Vav1 expression in A549 cells requires further study. Overall, the results of the present study revealed that TAOCSB may provide more information regarding lung cancer treatment.