Clinical Characteristics of Asthma Combined with COPD Feature

Purpose

In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD). The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.

Materials and Methods

A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV₁) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled. Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV₁/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up. We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data. All of the tests mentioned above were performed within one week.

Results

The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV₁/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV₁/FVC <70). The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group. Significantly lower FEV₁ and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group. Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.

Conclusion

Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function.     

Charlson Comorbidity Index Is an Important Prognostic Factor for Long-Term Survival Outcomes in Korean Men with Prostate Cancer after Radical Prostatectomy

Purpose

To analyze overall survival (OS), prostate cancer (PCa)-specific survival (PCaSS), and non-PCaSS according to the Charlson Comorbidity Index (CCI) after radical prostatectomy (RP) for PCa.

Materials and Methods

Data from 336 patients who had RP for PCa between 1992 and 2005 were analyzed. Data included age, preoperative prostate-specific antigen (PSA), prostate volume, clinical stage, and pathologic stage. Pre-existing comorbidities were evaluated by the CCI, and patients were classified into two CCI score categories (0, ≥1).

Results

The mean age of patients was 64.31±6.12 years. The median PSA value (interquartile range, IQR) was 11.30 (7.35 and 21.02) ng/mL with a median follow-up period (IQR) of 96.0 (85.0 and 121.0) months. The mean CCI was 0.28 (0-4). Five-year OS, PCaSS, and non-PCaSS were 91.7%, 96.3%, and 95.2%, respectively. Ten-year OS, PCaSS, and non-PCaSS were 81.9%, 92.1%, and 88.9%, respectively. The CCI had a significant influence on OS (p=0.022) and non-PCaSS (p=0.008), but not on PCaSS (p=0.681), by log-rank test. In multivariate Cox regression analysis, OS was independently associated with the CCI [hazard ratio (HR)=1.907, p=0.025] and Gleason score (HR=2.656, p<0.001). PCaSS was independently associated with pathologic N stage (HR=2.857, p=0.031), pathologic T stage (HR=3.775, p=0.041), and Gleason score (HR=4.308, p=0.001). Non-PCaSS had a significant association only with the CCI (HR=2.540, p=0.009).

Conclusion

The CCI was independently associated with both OS and non-PCaSS after RP, but the CCI had no impact on PCaSS. The comorbidities of a patient should be considered before selecting RP as a curative modality for PCa.     

Low-Dose Dexmedetomidine Reduces Emergence Agitation after Desflurane Anaesthesia in Children Undergoing Strabismus Surgery

Purpose

Emergence agitation (EA) is frequently observed in children undergoing general anaesthesia. This study tested whether the addition of an intra-operative low-dose infusion of dexmedetomidine to fentanyl treatment reduced the incidence of emergence delirium following desflurane anesthesia in children undergoing strabismus surgery.

Materials and Methods

A total of 96 children (1-5 years old) undergoing strabismus surgery were enrolled. Anaesthesia was induced with propofol and maintained with desflurane. After induction, fentanyl (1 µg/kg) was administered to all children. During surgery, patients were infused with 0.2 µg/(kg·h)^-1 dexmedetomidine (Group FD, n=47) or normal saline (Group F, n=47). Postoperative objective pain score (OPS), Paediatric Agitation and Emergence Delirium (PAED) score, and EA score were documented every 10 minutes in the post-anaesthesia care unit.

Results

There were no significant differences between the two groups in demographic characteristics and haemodynamic changes. The mean values of maximum EA, maximum PAED, and maximum OPS score were significantly lower in Group FD than in Group F at 0, 10, and 20 minutes after arrival at the post-anaesthesia care unit (p<0.001). The frequency of fentanyl rescue was lower in Group FD than in Group F (p<0.001). The incidence of severe EA was significantly lower in Group FD than in Group F (12.8% vs. 74.5%, p<0.001).

Conclusion

Intra-operative low-dose infusion of dexmedetomidine in addition to fentanyl reduces EA following desflurane anaesthesia in children undergoing strabismus surgeries.     

Is High-Dose Leuprorelin Acetate Effective and Safe in Asian Men with Prostate Cancer? An Open-Label,Non-Comparative,Multi-Center Clinical Trial

Purpose

Leuprorelin is a well known luteinizing hormone releasing hormone agonist. However, there are insufficient data on the efficacy and safety of high dose leuprorelin acetate, especially in Asian patients with prostate cancer. We aimed to investigate the safety and efficacy of leuprorelin acetate 22.5 mg administered at three-month intervals in patients with prostate cancer.

Materials and Methods

In an open, prospective clinical trial enrolling 47 patients, we aimed to assess the efficacy and safety of leuprorelin acetate 22.5 mg in treating patients with histologically confirmed prostate cancer. The primary objective of this study was to evaluate the efficacy of the leuprorelin acetate 22.5 mg in producing and maintaining castration levels of testosterone over a 6-month follow-up period and to determine its safety profile.

Results

All 42 patients achieved serum testosterone levels within the castration range by 4 weeks. A breakthrough response was observed in one of 36 patients by 8 weeks. However, this patient was medically castrated by 12 weeks. There were no significant prostate-specific antigen (PSA) or testosterone changes according to clinical stage or body mass index. Twenty adverse events (AEs) in 15 of 42 patients (35.7%) were observed during this study. The most common AEs were hot flushes (n=4, 20.0%) with mild intensity, pain (n=2, 10.0%), and infection (n=2, 10.0%). No patient withdrew from the study due to AEs.

Conclusion

Leuprorelin acetate 22.5 mg was shown to be effective and safe in Asian patients with prostate cancer, even though sexual function decreased.     

Antimycobacterial activity of Pichia pastoris-derived mature bovine neutrophil β-defensins 5

Tuberculosis (TB) is an ongoing threat to global health, and the lack of effective therapies for treating it is also a global problem. Previous studies have shown that human cathelicidin and defensins have effective antimicrobial activity against Mycobacterium spp. To our knowledge, there are no reports on the antimycobacterial effects of bovine neutrophil β-defensins so far. Here, we identified the antimicrobial effect of mature bovine neutrophil β-defensins (mBNBD) 5 against Mycobacterium infection both in vitro and in vivo. The mBNBD5 protein was expressed in Pichia pastoris. To increase the yield of β-defensins, a purification method was employed by adding a 6-His·tag to the C-terminus of the mBNBD5 gene. Our results indicated that recombinant mBNBD5 protein was successfully expressed and purified from Pichia pastoris with intact antimicrobial activity. The recombinant protein exhibited potent bactericidal activity in vitro against M. smegmatis and M. bovis, with a dose-dependent manner and a time-dependent manner. The electron microscope results showed that the bacterial cell wall of M. bovis was disrupted when incubated with mBNBD5 for 72 h. Our data also indicated that the exogenous addition of mBNBD5 could reduce the survival of Mycobacterium spp., especially M. tuberculosis and M. bovis in RAW 264.7 macrophages. These results provide foundations for the development of mBNBD5 as a potential new therapeutic agent for TB treatment.     

Apnea‐related sleep fragmentation and poor vigilance in children with well‐controlled asthma

It has been reported that sleep problems and neurocognitive deficit in asthmatic children is prevalent. However, systematic studies on these problems in stable asthma using polysomnography have rarely been performed. We therefore investigated sleep and neurocognitive functioning in children with well‐controlled asthma. Forty‐three children with well‐controlled, stable asthma and 31 controls (age range: 6–9 years) were enrolled in the study. Subjects were questioned for daytime sleepiness using the Paediatric Daytime Sleepiness Scale. Complete overnight polysomnography and neurocognitive function tests were performed on all subjects. Children with stable asthma had lower pulmonary function in comparison to their age‐matched controls. Asthmatic children had a higher apnea–hypopnea index (P < 0.001) and apnea–hypopnea‐related arousal index (P < 0.001) as compared with non‐asthmatics. Deep sleep was decreased in asthmatics (P = 0.001). In the vigilance test, the mean number of correct answers was lower (P = 0.005) and the mean reaction time was slower (P = 0.002) in asthmatic children. A hierarchical multiple linear regression showed that deep sleep and apnea–hypopnea‐related arousal index were significant predictors of vigilance. The data suggest that the prevalence of paediatric sleep‐disordered breathing and sleep fragmentation could be very high among children with well‐controlled asthma. Moreover, vigilance, the ability to maintain attention and alertness, was worse in stable asthmatic children when compared with healthy controls. Sleep‐disordered breathing should be checked even in stable asthmatic children as they are at risk for developing neurobehavioural deterioration associated with frequent arousals during sleep. Furthermore, early treatment for asthma may be required in order to prevent airway remodelling that could cause sleep problems.     

姜黄素对骨髓瘤细胞迁移和侵袭能力的影响及其机制研究

 目的：探讨姜黄素对骨髓瘤细胞迁移侵袭能力的影响及其机制。方法：shRNA表达质粒沉默含IQ模序的RasGTP酶活化蛋白1(IQ motif-containing GTPase-activating protein 1,IQGAP1)后转染RPMI8226细胞,Western blotting法检测RPMI8226-shIQGAP1组、RPMI8226-shRNA阴性对照组和未转染RPMI8226组细胞IQGAP1表达;不同浓度姜黄素作用于各组细胞后,Transwell迁移实验和Matrigel侵袭实验检测细胞的迁移及侵袭力,RT-PCR法检测姜黄素作用后IQGAP1 mRNA的表达,Western blotting检测姜黄素对各组细胞IQGAP1蛋白表达的影响。结果：使用shRNA表达质粒沉默IQGAP1后,RPMI8226细胞IQGAP1表达减少;RPMI8226-shIQGAP1组较RPMI8226-shRNA 阴性对照组和未转染RPMI8226 组细胞迁移及侵袭力下降,姜黄素可降低RPMI8226-shRNA 阴性对照组和未转染RPMI8226组细胞迁移及侵袭力,无浓度相关性,不同浓度的姜黄素对RPMI8226-shIQGAP1组作用后细胞的迁移及侵袭力无明显变化。对于RPMI8226-shRNA阴性对照组及未转染RPMI8226组,姜黄素作用后IQGAP1 mRNA及蛋白的表达下降。结论：姜黄素通过抑制IQGAP1的表达降低骨髓瘤细胞的迁移力和侵袭力。     

Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway exacerbates sepsis-induced immune deviation and immunosuppression

Sepsis is a life-threatening condition, but the pathophysiological basis and biomarkers for the monitoring of sepsis and as targets for therapy remain to be determined. We have shown previously that T cell immunoglobulin and mucin domain protein 3 (Tim-3), a negative immune regulator, is involved in the physiopathology of sepsis, but the underlying mechanisms remain unclear. In the present study, we showed that Tim-3 signalling modulated the response patterns of both macrophages and T helper cells in sepsis. Blockade of the Tim-3 pathway exacerbated sepsis-induced proinflammatory macrophage responses and lymphocyte apoptosis during the early phase of sepsis, and enhanced the shift to anti-inflammatory responses for both macrophages and T helper cells during the late phase of sepsis. Tim-3 signalling was found to regulate CD80 and CD86 expression on macrophages both in vivo and in vitro. Co-culture of T cells with Tim-3 knock-down macrophages led to a biased T helper type 2 (Th2) response, partially explaining how Tim-3 signalling shapes inflammation patterns in vivo. Further studies on this pathway might shed new light on the pathogenesis of sepsis and suggest new approaches for intervention.     

An efficient Au catalyst supported on hollow carbon spheres for acetylene hydrochlorination

Mesoporous hollow carbon spheres (HCSs) were prepared using SiO₂ spheres as a hard template, and Au nanoparticles were then synthesized using NaBH₄ as a reducing agent on the surface of the HCS support. Transmission electron microscopy characterization indicated that Au nanoparticles were much smaller on the HCS support than those on the active carbon (AC) support. HCl-TPD showed that the Au/HCS catalyst displayed a more active site than on Au/AC. The resulting Au/HCS catalyst showed excellent catalytic activity and stability for acetylene hydrochlorination. Acetylene conversion of Au/HCS can be maintained above 92% even after 500 h of lifetime. The excellent catalytic performance of Au/HCS was attributed to the presence of the HCS support, which limited the aggregation of Au nanoparticles.

Mesoporous hollow carbon spheres (HCS) were prepared and applied as the support of Au catalyst for acetylene hydrochlorination. Au/HCS exhibited excellent stability for acetylene hydrochlorination.     

Vaccinia‐based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection

Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell‐based vaccine, but the narrow breadth of T‐cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T‐cell immunodominance hierarchy in humans in an experimental setting, influenza‐primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN‐γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T‐cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD₅₀ challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP₃₆₆ epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV‐NP + PA showed improved protection. Taken together, a vaccinia‐based influenza vaccine expressing conserved internal proteins improved the breadth of influenza‐specific T‐cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains.