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A bstract Rationale: New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection. Methods: The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia. Results: ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2, ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well. Conclusions: In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2, which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa. S tem C ells 2015;33:2331-2342 [ABSTRACT FROM AUTHOR]

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines., Competing Interests: Conflict of interest: W-J. Guan reports consulting fees from Joincare Pharmaceutical Co. Ltd., lecture fees from Joincare Pharmaceutical Co. Ltd., support for travel to attend domestic meetings from Joincare Pharmaceutical Co. Ltd., and is an associate editor of this journal. Conflict of interest: S.H. Chotirmall reports grants paid to his institution from the Singapore Ministry of Education, National Medical Research Council Singapore, consulting fees from CSL Behring, Pneumagen Ltd, Boehringer Ingelheim and Pneumagen Ltd, lecture fees from AstraZeneca and Chiesi, and participation in Data Safety and Monitoring Committees for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University. Conflict of interest: J.D. Chalmers reports grants from GSK, Boehringer Ingelheim, Genentech, Insmed, Grifols, Novartis, Gilead and AstraZeneca, consulting fees from AstraZeneca, Grifols, Genentech, GSK, Chiesi, Zambon, Trudell and Pfizer, and is an associate editor of this journal. Conflict of interest: J.F. Xu reports consulting fees from AstraZeneca and Boehringer Ingelheim. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Objectives: To investigate the prevalence of heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) and the sensitivity of hVISA to novel antibiotics, and to explore the risk factors and infection attributable mortality associated with hVISA infection., Methods: A total of 456 methicillin resistant Staphylococcus aureus (MRSA) isolates were isolated in Zhongshan Hospital from January, 2008 to November, 2010. All MRSA isolates were investigated for hVISA by two agar screening methods BHIA5T (brain-heart infusion containing teicoplanin 5 mg/L) or BHIA6V (brain-heart infusion containing vancomycin 6 mg/L), as well as macroEtest method (MET). Possible hVISA isolates were tested by modified population analysis profile-area under the curve (PAP-AUC). The minimal inhibitory concentrations (MICs) of vancomycin, teicoplanin and linezolid were determined by microbroth dilution as recommended by Clinical Laboratory Standards Institute (CLSI). The contribution difference between hVISA and vancomycin susceptible Staphylococcus aureus (VSSA) in different MIC range was compared. A retrospective case-control study of the patients with hVISA infection or VSSA infection was carried out and statistical analysis was performed using t test, Mann-Whitney test, χ(2) test and Fisher exact test., Results: A total of 105 isolates of hVISA were screened by BHIA5T and BHIA6V (23.0%) with other 23 isolates by MET (5.0%) and 21 by PAP-AUC (4.6%). All isolates were 100% sensitive to vancomycin, teicoplanin and linezolid. The vancomycin MIC [(1.76 ± 0.16) mg/L] in hVISA group was significantly higher than that in VSSA group [(1.09 ± 0.07) mg/L, P < 0.01], which was a potential risk factor for hVISA infection. The retrospective study showed chronic obstructive pulmonary disease (COPD) was also a risk factor for hVISA infection of the lower respiratory tract. No significant difference in infection attributable mortality was showed between the hVISA group and the VSSA group., Conclusions: The overall prevalence of hVISA in Zhongshan Hospital is estimated as 4.6%, while the prevalence of hVISA isolated from blood is as high as 12.5%. All isolates are 100% sensitive to vancomycin and linezolid. COPD is a risk factor for hVISA infection of the lower respiratory tract.

Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the 'MIOTIC study' to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management.

Aim: Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC), and the underlying mechanism remains unclear. FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients. In this study, we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms., Methods: Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used. mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis. RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells, and lentiviral infection was used to overexpress FoxM1 in H292 cells. MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells., Results: Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentration-dependent manners, while gefitinib (1 μmol/L) downregulated in H292 cells. In SPC-A-1 cells treated with gefitinib (1 μmol/L), the expression of several downstream targets of FoxM1, including survivin, cyclin B1, SKP2, PLK1, Aurora B kinase and CDC25B, were significantly upregulated. Overexpression of FoxM1 increased the resistance in H292 cells, while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis., Conclusion: The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro. FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

Aim: To investigate the role of aquaporin-1 (AQP1) and sodium channel on pleural fluid transport., Methods: Wild-type and AQP1 null mice were used in this study. After the mice were briefly anesthetized, 0.25 mL of hyperosmolar or isosmolar solution (containing terbutaline, amiloride or saline only) was infused into the pleural space. Then mice were sacrificed at scheduled times for measurement of pleural fluid osmolality or volume., Results: After instillation of hyperosmolar fluid into the pleural space, the osmolality of pleural fluid in wild-type mice was higher than that in AQP1 null mice killed at the same time (1, 2, 5 min). There was no difference in the isosmolar clearance between the wild-type and AQP1 null mice after injection of 0.25 mL isosmolar fluid into the pleural space. Terbutaline increased the osmotic and isosmolar fluid transport across pleura, but these effects were not influenced by AQP1 deletion. In contrast, amiloride reduced osmotic and isosmolar pleural fluid transport, and these effects were not influenced by AQP1 deletion., Conclusion: AQP1 water channels facilitated osmotic fluid transport across the pleural surface. However, AQP1 did not play an important role in pleural isosmolar fluid clearance. Sodium channel may play a role in osmotic and isosmolar pleural fluid transport. The effects of sodium channel on fluid transport across pleural space were not influenced by aquaporin-1 deletion.

In the ethanol/water medium containing 0.1 mol.L-1 ammonium acetate (NH4Ac) and 1.5% (w/v) sodium dodecyl sulfate (SDS), the complex chromogenic reaction of trace Cu (II) with 5, 8-dihydroxy-1, 4-naphthoquinone (Naph) has been studied. Based on this study, a novel spectrophotometric method for determining trace Cu (II) has been developed. The results show that the maximum absorption of the colored complex is at 330 nm, the molar absorptivity is 1.8 x 10(4) L.mol-1.cm-1, the detection limit of the method is 0.3 mg.L-1 for Cu (II) and Beer's law is obeyed for Cu (II) in the range of 0.0-4.5 mg.L-1. The linear regress equation of A is 0.290 CCu(II) (mg.L-1) +0.015, the correlation coefficient is 0.9981, the standard recovery of Cu (II) is in the range of 97.9%-104.1% (n = 6) and the relative standard deviation (RSD) is in range of 1.6%-5.1% (n = 6). Both of the precision and accuracy are suitable to microanalysis. The method was applied to trace copper determination in dry tea samples with satisfactory results.

Objective: To investigate the effect of sodium channel and aquaporin-1 on pleural fluid transport., Methods: Mice were briefly anesthetized, and the pleural space was infused with 0.25 ml of hyperosmolar or isosmolar solution, with terbutaline or amiloride in instilled solution. The mice were treated with either intraperitoneal dexamethasone or intravenous HgCl(2). Mice were euthanized at specified times for measurement of pleural fluid osmolality, volume and (125)I-album in concentration. The rate of pleural fluid filtration and clearance was calculated, which was used to indicate the effect of sodium channel regulator (amiloride and terbutaline) and aquaporin regulator (dexamethasone and HgCl(2)) on pleural fluid transport., Results: Amiloride decreased the osmotically driven water transport and isosmolar fluid clearance in pleural space (P < 0.05). Terbutaline increased osmotically driven water transport and isosmolar fluid clearance in pleural space (P < 0.05). HgCl(2) decreased, while dexamethasone increased, the osmotically driven water transport in pleural space (P < 0.05). HgCl(2) and dexamethasone had no effect on pleural isosmolar fluid clearance (P > 0.05)., Conclusions: Sodium channel may play a role in osmotic and isosmolar fluid transport in pleural space. Aquaporin-1 may play a role in osmotic fluid transport in pleural space, while having no effect on isosmolar fluid clearance.