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Objectives: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA)., Methods: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence., Results: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance., Conclusion: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA., (© 2024 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: This scoping review aimed to characterise near-death experiences in the setting of cardiac arrest, a phenomenon that is poorly understood and may have clinical consequences., Method: PubMed/MEDLINE was searched to 23 July 2023 for prospective studies describing near-death experiences in cardiac arrest. PRISMA-ScR guidelines were adhered to. Qualitative and quantitative data were synthesised. Meta-analysis was precluded due to data heterogeneity., Results: 60 records were identified, of which 11 studies involving interviews were included from various countries. Sample size ranged from 28-344, and proportion of female patients (when reported) was 0-50%, with mean age (when reported) ranging 54-64 years. Comorbidities and reasons for cardiac arrest were heterogeneously reported. Incidence of near-death experiences in the included studies varied from 6.3% to 39.3%; with variation between in-hospital (6.3-39.3%) versus out-of-hospital (18.9-21.2%) cardiac arrest. Individual variables regarding patient characteristics demonstrated statistically significant association with propensity for near-death experiences. Reported content of near-death experiences tended to reflect the language of the questionnaires used, rather than the true language used by individual study participants. Three studies conducted follow-up, and all suggested a positive life attitude change, however one found significantly higher 30-day all-cause mortality in patients with near-death experiences versus those without, in non-controlled analysis., Conclusions: From prospective studies that have investigated the phenomenon, near-death experiences may occur in as frequent as over one-third of patients with cardiac arrest. Lasting effects may follow these events, however these could also be confounded by clinical characteristics., (© 2024. The Author(s).)

Background: In calcaneal fractures, the percutaneous screw fixation (PSF) is currently considered to be the better choice, but it is difficult to accurately place the screw into the sustentaculum tali (ST) during the operation. In this study, the ideal entry point, angle, diameter and length of the screw were calculated by simulating the operation process., Methods: We retrospectively collected the calcaneus computed tomography (CT) scans of 180 adults, DICOM-formatted CT-scan images of each patient were imported into Mimics software to establish calcaneus model. Virtual screws were placed on the lateral of the posterior talar articular surface (PTAS), the lateral edge of the anterior process of calcaneus (APC), and the calcaneal tuberosity, respectively, the trajectory and size of the screws were calculated., Results: The mean maximum diameter of the PTAS screw was 42.20 ± 3.71 mm. The vertical distance between the midpoint of the APC optimal screw trajectory and the lowest point of the tarsal sinus was 10.67 ± 1.84 mm, and the distance between the midpoint of the APC optimal screw trajectory and the calcaneocuboid joint was 5 mm ~ 19.81 ± 2.08 mm. The mean maximum lengths of APC screws was 44.69 ± 4.81 mm, and the Angle between the screw and the coronal plane of the calcaneus from proximal to distal was 4.72°±2.15° to 20.52°±3.77°. The optimal point of the maximum diameter of the calcaneal tuberosity screw was located at the lateral border of the achilles tendon endpoint. The mean maximum diameters of calcaneal tuberosity screws was 4.46 ± 0.85 mm, the mean maximum lengths of screws was 65.31 ± 4.76 mm. We found gender-dependent differences for the mean maximum diameter and the maximum length of the three screws., Conclusions: The study provides effective positioning for percutaneous screw fixation of calcaneal fractures. For safer and more efficient screw placement, we suggest individualised preoperative 3D reconstruction simulations. Further biomechanical studies are needed to verify the function of the screw., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is an established site for green herbicide discovery. In this work, based on structural analysis, we develop an active fragment exchange and link (AFEL) approach to designing a new class of N -1,4-diketophenyltriazinones I - III as potent Nicotiana tabacum PPO (PPO) inhibitors. After systematic structure-activity relationship optimizations, a series of new compounds with K i values in the single-digit nanomolar range toward NtPPO and promising herbicidal activity were discovered. Among them, Ii ( K i = 0.11 nM) displays 284- and 90-fold improvement in NtPPO inhibitory activity over trifludimoxazin ( K i = 31 nM) and saflufenacil ( K i = 10 nM), respectively. In addition, Ip ( K i = 2.14 nM) not only exhibited good herbicidal activity at 9.375-37.5 g ai/ha but also showed high crop safety to rice at 75 g ai/ha by the postemergence application, indicating that Ip could be developed as a potential herbicide for weed control in rice fields. Additionally, our molecular dynamic simulation clarified the molecular basis for the interactions of these molecules with NtPPO. The metabolism studies in planta showed that IIIc could be converted to Ic , which displayed higher herbicidal activity than IIIc . The density functional theory analysis showed that due to the effect of two sulfur atoms at the triazinone moiety, IIIc is more reactive than Ic , making it more easily degraded in planta . Our work indicates that the AFEL strategy could be used to design new molecules with improved bioactivity.

Bacteria depend on the ferrous iron transport (Feo) system for the uptake of ferrous iron (Fe 2+ ). The Feo system is crucial for colonization and virulence of pathogens. In γ-proteobacteria, the system consists of FeoA, FeoB, and FeoC. The function of FeoA remains unknown. FeoB likely forms the channel, whose regulation has been suggested to involve its GTPase domain (part of its NFeoB domain). FeoC from Klebsiella pneumonia was found to contain a [4Fe4S] cofactor, whose presence was speculated to enhance the GTPase activity of FeoB (Hsueh, K.-L., et al., J. Bacteriol. 2013 195(20): 4726-34). We present results here that support and extend that hypothesis. We monitored the GTPase activity of FeoB by NMR spectroscopy and found that the presence of 7% FeoC-[4Fe-4S] 3+ (the highest level of cofactor achieved in vitro) increased the GTPase rate of NFeoB by 3.6-fold over NFeoB. The effect depends on the oxidation state of the cluster; with reduction of the cluster to [4Fe-4S] 2+ the GTPase greatly decreased the GTPase rate. From the effects of point mutations in FeoC on GTPase rates, we conclude that Lys62 and Lys68 on FeoC each contribute to increased GTPase activity on NFeoB. Mutation of Thr37 of NFeoB to Ser nearly abolished the GTPase activity. The GTPase activity of the isolated K. pneumoniae NFeoB-FeoC complex (NFeoBC) was found to be higher in KCl than in NaCl solution. We solved the X-ray structure of the NFeoBC crystallized from KCl and compared it with a prior X-ray structure crystalized from NaCl. We propose a hypothesis, consistent with these results, to explain the factors that influence the GTPase activity. Bacteria may use the oxygen-sensitive cluster as a sensor to up-regulate the gate closing speed., Competing Interests: Declaration of competing interest The authors declare no competing financial interests. The experiments were conducted at the Institute of Biomedical Sciences, Academia Sinica, and National Synchrotron Radiation Research Center, Hsinchu, Taiwan., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The choriocapillaris plays a considerable role in the normal physiology of the eye as well as in various diseases. Assessing the changes in the choriocapillaris can therefore provide important information about normal ageing and pathogenesis of visual impairment, and even some systemic diseases. In vivo imaging of the choriocapillaris has evolved from non-depth resolved, dye-based angiography to advanced, high-resolution optical coherence tomography angiography (OCTA). However, the intricate microvascular networks within the choriocapillaris are still beyond the resolving limits of most OCTA instruments. Knowledge of histology, meticulous image acquisition methods, recognition of artefact and post-acquisition processing techniques are necessary for optimising OCTA choriocapillaris images. Qualitative and quantitative analyses of the choriocapillaris provide clinical information in age-related macular degeneration (AMD), diabetic retinopathy (DR), pathologic myopia and central serous chorioretinopathy (CSC). Furthermore, studies have revealed choriocapillaris changes in posterior uveitis that are correlated with treatment outcome and have important prognostic significance. In addition to retinal diseases, choriocapillaris changes have been observed in systemic vascular diseases and complications associated with pregnancy., (© 2021 Royal Australian and New Zealand College of Ophthalmologists.)

The manufacturing of 3D and conformal metamaterials remains a major challenge. The projection micro-stereolithography 3D printing technology combined with the liquid metal filling method is employed here to fabricate the metamaterials, which are characterized with embedded features that can effectively protect the metal resonance layer from external influence, and integrated molding of macro-micro structures and function-structure. To demonstrate the robustness and flexibility of the proposed method, three types of metamaterials are fabricated: 3D orthogonal split-ring resonator metamaterial, bionic compound eye conformal metamaterial, and a five-layer broadband conformal metamaterial in the form of hemispherical moth-eye, which are costly, tedious, and time consuming in conventional fabrication methods. And the layout of the filling channel is optimized and the polydimethylsiloxane coating post-treatment process is applied to smooth the surface roughness caused by the staircase effect of 3D printing to improve the transmission performance of metamaterial devices. The transmission properties are measured using terahertz time-domain spectroscopy system and the experimental results show that the method proposed in this paper makes metamaterial manufacture no longer limited to complex structures, which effectively expands the application range of metamaterials., (© 2021 Wiley-VCH GmbH.)

Autologous chondrocyte (CH) transplantation is a novel strategy to treat post-traumatic osteoarthritis (PTOA). In this study, an in vitro coculture model was used to explore the effects of interleukin (IL)-10 overexpressed CHs on degenerated CHs. The original CHs were isolated from the patients' knee joint cartilage and pretreated with IL-1β to get degenerated CHs. Moreoer, CHs were transfected with a lentivirus vector to overexpress IL-10. After coculture with the degenerated CHs, the apoptosis, collagen X, IL-6, and TNF-α of original CHs were increased, and the collagen II and IL-10 were decreased compared to the separated culture condition. Coculture with original CHs did not alleviate the degeneration of the IL-1β-pretreated CHs. However, coculture with the IL-10-overexpressed CHs rescued the proliferation, collagen II, aggrecan, SOX9, and IL-10 expression, and suppressed the apoptosis, collagen X, RUnx2, IL-6, and TNF-α levels in the IL-1β pretreated CHs. Additionally, the IL-10-overexpressed CHs also maintained a healthy state when cocultured with the degenerated CHs. Therefore, transplanting the IL-10-overexpressed CHs in the treatment of PTOA would obtain a more durable and visible effect in alleviating the CH degeneration., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Background: The development of 3D cerebral organoid technology using human-induced pluripotent stem cells (iPSCs) provides a promising platform to study how brain diseases are appropriately modeled and treated. So far, understanding of the characteristics of organoids is still in its infancy. The current study profiled, for the first time, the electrophysiological properties of organoids at molecular and cellular levels and dissected the potential age equivalency of 2-month-old organoids to human ones by a comparison of gene expression profiles among cerebral organoids, human fetal and adult brains., Results: Cerebral organoids exhibit heterogeneous gene and protein markers of various brain cells, such as neurons, astrocytes, and vascular cells (endothelial cells and smooth muscle cells) at 2 months, and increases in neural, glial, vascular, and channel-related gene expression over a 2-month differentiation course. Two-month organoids exhibited action potentials, multiple channel activities, and functional electrophysiological responses to the anesthetic agent propofol. A bioinformatics analysis of 20,723 gene expression profiles showed the similar distance of gene profiles in cerebral organoids to fetal and adult brain tissues. The subsequent Ingenuity Pathway Analysis (IPA) of select canonical pathways related to neural development, network formation, and electrophysiological signaling, revealed that only calcium signaling, cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling in neurons, glutamate receptor signaling, and synaptogenesis signaling were predicted to be downregulated in cerebral organoids relative to fetal samples. Nearly all cerebral organoid and fetal pathway phenotypes were predicted to be downregulated compared with adult tissue., Conclusions: This novel study highlights dynamic development, cellular heterogeneity and electrophysiological activity. In particular, for the first time, electrophysiological drug response recapitulates what occurs in vivo, and neural characteristics are predicted to be highly similar to the human brain, further supporting the promising application of the cerebral organoid system for the modeling of the human brain in health and disease. Additionally, the studies from these characterizations of cerebral organoids in multiple levels and the findings from gene comparisons between cerebral organoids and humans (fetuses and adults) help us better understand this cerebral organoid-based cutting-edge platform and its wide uses in modeling human brain in terms of health and disease, development, and testing drug efficacy and toxicity.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been identified as one of the most significant targets in herbicide discovery for resistant weed control. In a continuing effort to discover potent novel HPPD inhibitors, we adopted a ring-expansion strategy to design a series of novel pyrazole-quinazoline-2,4-dione hybrids based on the previously discovered pyrazole-isoindoline-1,3-dione scaffold. One compound, 3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1 H -pyrazole-4-carbonyl)-1,5-dimethylquinazoline-2,4(1 H ,3 H )-dione ( 9bj ), displayed excellent potency against At HPPD, with an IC 50 value of 84 nM, which is approximately 16-fold more potent than pyrasulfotole (IC 50 = 1359 nM) and 2.7-fold more potent than mesotrione (IC 50 = 226 nM). Furthermore, the co-crystal structure of the At HPPD- 9bj complex (PDB ID 6LGT) was determined at a resolution of 1.75 Å. Similar to the existing HPPD inhibitors, compound 9bj formed a bidentate chelating interaction with the metal ion and a π-π stacking interaction with Phe381 and Phe424. In contrast, o -chlorophenyl at the N3 position of quinazoline-2,4-dione with a double conformation was surrounded by hydrophobic residues (Met335, Leu368, Leu427, Phe424, Phe392, and Phe381). Remarkably, the greenhouse assay indicated that most compounds displayed excellent herbicidal activity (complete inhibition) against at least one of the tested weeds at the application rate of 150 g of active ingredient (ai)/ha. Most promisingly, compounds 9aj and 9bi not only exhibited prominent weed control effects with a broad spectrum but also showed very good crop safety to cotton, peanuts, and corn at the dose of 150 g of ai/ha.

Introduction: Macrophage inhibitory cytokine-1 (MIC-1), a transforming growth factor-β superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis of a wide range of cancers., Objectives: The aim of this study was to explore the diagnostic value of serum MIC-1 in patients with solitary pulmonary nodules (SPNs)., Methods: Serum specimens from 158 malignant SPN patients, 110 benign SPN patients, along with 120 healthy volunteers. The levels of serum MIC-1 were measured by sandwich enzyme-linked immunosorbent assay., Results: Serum levels of MIC-1 in malignant SPN patients were significantly higher than those in benign SPN patients (P < .01), or those in healthy volunteers (P < .01). With a cutoff of 685.8 pg/ml, the sensitivity and specificity of MIC-1 in differentiating between malignant SPN patients and benign SPN patients, and between malignant SPN patients and healthy volunteers was, 56.3% and 92.7%, and 65.8% and 96.7%, respectively. An area under the curve (AUC) for malignant SPN resulting from MIC-1, which was significantly better than any other tumor markers tested including carbohydrate antigens 12-5 (CA125), and carcinoembryonic antigen (CEA)., Conclusions: In conclusion, measurement of serum MIC-1 levels could be considered as a diagnostic biomarker for malignant SPN patients., (© 2017 John Wiley & Sons Ltd.)

Introduction: For thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years., Objectives: Mutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti-EGFR therapies., Methods: Genomic DNA was extracted from 61 histological samples of TCs. Real-time polymerase chain reaction (PCR) and direct sequencing were used to assess the mutations in the EGFR downstream pathway., Results: Gene mutations were identified in seven patients (11.5%). In particular, the identified mutations included four mutations in the KRAS gene, one mutation in the BRAF gene, one mutation in the PIK3CA gene, and only one mutation in the EGFR gene itself. Gene mutations in the EGFR downstream pathway were associated with shorter survival time and were observed to be an independent prognostic factor for TC patients., Conclusion: Mutations in the EGFR downstream pathway are not rare in TCs. These data offer interesting possibilities for the future management of TCs, particularly in the era of new targeted therapies., (© 2016 John Wiley & Sons Ltd.)

Background: Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and is associated with invasiveness and metastasis in breast cancer. However, its relevance in non-small cell lung cancer (NSCLC) remained largely unknown., Methods: LOXL2 protein levels in a cohort of NSCLC and adjacent normal lung tissues were evaluated and analyzed their clinicopathologic and prognostic significance., Results: It was found that cytoplasmic and nuclear LOXL2 levels were higher in lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) tissues than in paired adjacent normal tissues. High LOXL2 levels were associated with p-TNM stage, and cytoplasmic, but not nuclear, LOXL2 levels were an independent prognostic factor in lung AD and SCC patients., Conclusion: These results demonstrate that elevated LOXL2 levels are positively associated with poor prognosis in NSCLC patients. LOXL2 might, therefore, serve as a novel prognostic biomarker and potential therapeutic target in NSCLC patients., (© 2016 John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is characterized by neuritic plaques and neurofibrillary tangles. It is reported that enzymatic degradation of amyloid-β (Aβ) plays a pivotal role in Aβ accumulation and type-2 cannabinoid receptor (CB2R) participates in Aβ processing in the brain; however, the underlying mechanisms remain unclear. We determined that Aβ degradation-related proteins are significantly different between CB2R-/- mice and wild-type (WT) mice via proteomic analysis. Moreover, the data demonstrated that the angiotensin converting enzyme (ACE) and insulin-degrading enzyme (IDE) levels are substantially attenuated, and the Aβ level is significantly enhanced in CB2R-/--Aβ1 - 42 mice compared with that of WT-Aβ1 - 42 mice. Furthermore, Aβ-mediated synaptic dysfunction, the loss of memory associated proteins, and the suppression of glutamatergic transmission are more severe in CB2R-/--Aβ1 - 42 mice than that in WT-Aβ1 - 42 mice. CB2R activation could decrease Aβ1 - 40 and Aβ1 - 42 levels and enhance ACE and IDE levels with its selective agonist JWH133; however, AM630 (CB2R antagonist) abrogates all changes induced by JWH133 in N2a cells with AβPP overexpression. Taken together, our study demonstrated that the deletion of CB2R reduces exogenous Aβ degradation and aggravates the toxicity of Aβ via the reduction of ACE and IDE, which suggests that CB2R is involved in the onset of AD and a potential therapeutic target for AD.

Background: Interprofessional learning is gaining momentum in revolutionizing healthcare education. During the academic year 2015/16, seven undergraduate-entry health and social care programs from two universities in Hong Kong took part in an interprofessional education program. Based on considerations such as the large number of students involved and the need to incorporate adult learning principles, team-based learning was adopted as the pedagogy for the program, which was therefore called the interprofessional team-based learning program (IPTBL). The authors describe the development and implementation of the IPTBL program and evaluate the effectiveness of the program implementation., Methods: Eight hundred and one students, who are predominantly Chinese, participated in the IPTBL. The quantitative design (a pretest-posttest experimental design) was utilized to examine the students' gains on their readiness to engage in interprofessional education (IPE)., Results: Three instructional units (IUs) were implemented, each around a clinical area which could engage students from complementary health and social care disciplines. Each IU followed a team-based learning (TBL) process: pre-class study, individual readiness assurance test, team readiness assurance test, appeal, feedback, and application exercise. An electronic platform was developed and was progressively introduced in the three IUs. The students' self-perceived attainment of the IPE learning outcomes was high. Across all four subscales of RIPLS, there was significant improvement in student's readiness to engage in interprofessional learning after the IPTBL. A number of challenges were identified: significant time involvement of the teachers, difficulty in matching students from different programs, difficulty in making IPTBL count towards a summative assessment score, difficulty in developing the LAMS platform, logistics difficulty in managing paper TBL, and inappropriateness of the venue., Conclusions: Despite some challenges in developing and implementing the IPTBL program, our experience showed that TBL is a viable pedagogy to be used in interprofessional education involving hundreds of students. The significant improvement in all four subscales of RIPLS showed the effects of the IPTBL program in preparing students for collaborative practice. Factors that contributed to the success of the use of TBL for IPE are discussed.

Introduction: Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined., Objectives: The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC., Methods: Serum specimens from 592 NSCLC patients, 180 benign lung disease patients and 240 healthy controls were collected. The concentrations of CR-1 were measured by sandwich enzyme-linked immunosorbent assay., Results: Patients with NSCLC had higher serum CR-1 levels than the controls (P < 0.01) and patients with benign lung diseases (P < 0.01). When a cutoff point of 1.8 ng/mL was selected (diagnostic specificity 95%), the diagnostic sensitivity for NSCLC is 56.8%. About 37.5% of carcinoembryonic antigen (CEA)-negative lung cancer patients were CR-1 positive at 95% specificity. In patients with stage I/II lung cancer, use of these two markers in combination results in almost 21% increase in sensitivity, at 95% specificity, compared with CEA alone. Uni-variate analysis revealed that NSCLC patients with positive CR-1 had a shorter overall survival (OS) and progression-free survival (PFS) than those with negative CR-1 [hazard ratio (HR) of 2.93, P = 0.005; HR of 2.12, P = 0.005]. Cox multi-variate analysis indicated that CR-1 was an independent prognostic indicator of PFS and OS (HR of 1.91, P = 0.006; HR of 1.82, P = 0.007). Kaplan-Meier survival curves further confirmed that patients with negative CR-1 had longer PFS and OS (P = 0.026 and P = 0.011, respectively)., Conclusions: In conclusion, measurement of serum CR-1 is a useful diagnostic and prognostic marker for NSCLC patients., (© 2015 John Wiley & Sons Ltd.)

The aim of this study was to assess the usefulness of endobronchial ultrasound transbronchial biopsy with guide-sheath (EBUS-GS-TBB) for the diagnosis of solitary pulmonary nodules (SPNs). One hundred and eighty patients, who were diagnosed with SPNs and underwent an endobronchial ultrasound procedure. The diagnostic yield, safety and the associated factors were analyzed. Mean EBUS-GS procedure time was 14±8 min. The average number of biopsy specimens obtained in each SPNs was 5±1.2. One hundred and thirty-four SPNs were diagnosed by EBUS-GS-TBB and the diagnostic rate was 74.4 %. The diagnosis rate of malignancy was 83.3 %, while that of benign disease was 56.7 %. The most important factors that helped enhance EBUS-GS diagnostic accuracy included lesion diameter greater than 20mm, EBUS probe within the lesions and central lesions. No pneumothorax, hemoptysis or other serious complications occurred with the diagnostic procedures. EBUS-GS-TBB is a safe and effective method for diagnosing SPNs., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

The periostin protein is expressed in a variety of human malignancies. The aim of this study was to explore the diagnostic and prognostic value of serum periostin levels in patients with non-small cell lung cancer (NSCLC). We measured serum periostin levels by ELISA in 296 NSCLC patients, 120 benign lung diseases (BLD) patients and 160 healthy controls. The levels of serum periostin in NSCLC patients were significantly elevated compared with those in healthy controls (P < 0.001) and BLD patients (P < 0.001). Using a cutoff value of 30.87 ng/ml, the sensitivity and specificity of periostin in differentiating between NSCLC patients and BLD patients, and between NSCLC patients and healthy controls was, 48.6 and 91.7%, and 51.4 and 97.5%, respectively. Kaplan-Meier log rank analysis revealed that the higher serum periostin levels group had a poorer progression-free survival (PFS) and overall survival (OS) compared with lower periostin group (P = 0.024, P = 0.015, respectively). Further univariate and multivariate Cox regression analysis showed that serum periostin was an independent risk factor of prognosis of NSCLC patients. In conclusion, our study suggests that serum periostin could be considered as a diagnostic and prognostic marker for NSCLC patients.

The aim of this study was to assess the clinical value of radial probe endobronchial ultrasound (RP-EBUS)-guided localization of solitary pulmonary nodules (SPNs) with the combination of ultrathin bronchoscopy and methylene blue prior to video-assisted thoracoscopic surgery (VATS). An ultrathin bronchoscope was used to localize the lesions under RP-EBUS guidance in 48 patients (18 men and 30 women; age range, 41-72 years; mean age, 54 years), who subsequently underwent VATS resection. The lesion size, distance from the parietal pleura, localization time and complications were evaluated. The RP-EBUS-guided localization success rate was 72.9%. The lesion size ± standard deviation was 12.8±4.2 mm and the mean distance from the parietal pleura was 11.2±9.7 mm. The mean localization time was 15.7±8.3 min. The major complication of RP-EBUS-guided localization was asymptomatic hemorrhage in 4 patients (8.3%). The VATS resection success rate was 95.8%. In terms of pathological type, the 48 lesions included atypical adenomatous hyperplasia (n=4), adenocarcinoma in situ (n=5), minimally invasive adenocarcinoma (n=7), adenocarcinoma (n=18), squamous cell carcinoma (n=1), inflammation (n=6), hamartoma (n=4) and tuberculosis (n=3). Therefore, RP-EBUS-guided localization with the combination of an ultrathin bronchoscope and methylene blue prior to VATS resection is a promising technique for SPNs, it plays an important role in the accurate localization of SPNs and it is an effective and safe technique to assist VATS resection of such nodules.

Objectives: The present study aimed to investigate the synergistic action of telmisartan and linagliptin in ameliorating pancreatic islet functions and morphology in type 2 diabetes mellitus and to delineate the molecular signaling pathway involved., Methods: db/db mice were given telmisartan (3 mg/kg) or linagliptin (3 mg/kg) alone or in combination, daily for 8 weeks, and were studied in vivo by fasting and random blood glucose tests, oral glucose tolerance tests, and intraperitoneal insulin tolerance tests, as well as ex vivo by glucose-stimulated insulin secretion and morphology of pancreatic islets. The underlying signaling pathways were examined by Western blot, real-time quantitative polymerase chain reaction, and dihydroethidium staining analyses using mouse pancreatic islets and rat β-insulinoma cells., Results: Telmisartan/linagliptin combination induced significantly better glucose homeostasis than the monotherapies. Posttreatment reactive oxygen species level was suppressed most significantly after the telmisartan/linagliptin combined therapy, whereas no significant change in peroxisome proliferator-activated receptor γ expressions was observed after treatments., Conclusions: The telmisartan/linagliptin combination preserved pancreatic islet cell functions and morphology via reduction of oxidative stress but independent of the peroxisome proliferator-activated receptor γ pathway. Our data shed light on the therapeutic potential of using the telmisartan/linagliptin combination in the treatment of human type 2 diabetes mellitus and its related complications.

Glucose is the prominent molecule that characterizes diabetes and, like the vast majority of nutrients in our diet, it is absorbed and enters the bloodstream directly through the small intestine; hence, small intestine physiology impacts blood glucose levels directly. Accordingly, intestinal regulatory modulators represent a promising avenue through which diabetic blood glucose levels might be moderated clinically. Despite the critical role of small intestine in blood glucose homeostasis, most physiological diabetes research has focused on other organs, such as the pancreas, kidney, and liver. We contend that an improved understanding of intestinal regulatory mediators may be fundamental for the development of first-line preventive and therapeutic interventions in patients with diabetes and diabetes-related diseases. This review summarizes the major important intestinal regulatory mediators, discusses how they influence intestinal glucose absorption, and suggests possible candidates for future diabetes research and the development of antidiabetic therapeutic agents., (Copyright © 2015 the American Physiological Society.)

Background: Cripto-1 (CR-1) plays an important role in angiogenesis related to tumor growth, in concert with vascular endothelial growth factor (VEGF), and enhanced expression of CR-1 has been reported in lung cancer tissue., Methods: Patients with lung cancer (n = 156) and healthy volunteers (n = 60) were enrolled in the study. Serum CR-1 and VEGF concentrations were measured using enzyme-linked immunosorbent assay., Results: Patients with lung cancer had higher serum CR-1 (4.03 ± 1.49 ng/mL vs. 1.13 ± 0.43 ng/mL, p&lt;0.05) and VEGF (503.62 ± 112.74 pg/mL vs. 398.62 ± 117.84 pg/mL, p&lt;0.05) levels than the control group. With stage progression in non-small cell lung cancer (NSCLC), serum CR-1 levels increased, and patients with distant metastasis had higher levels than those without metastasis (p&lt;0.05). In NSCLC, the low CR-1 group (&lt;1.54 ng/mL) had a better overall survival rate compared with the high CR-1 group (&gt;1.54 ng/mL, p&lt;0.05)., Conclusions: Our study suggests that serum CR-1 is a useful diagnostic and prognostic marker for NSCLC patients.

Background: Iron may contribute to vascular injury through reactive oxygen species. Hemodialysis patients frequently receive iron supply for correction of anemia and are at a high risk of cardiovascular disease. We tested the relationship between iron status and change in arterial stiffness in hemodialysis patients., Patients and Methods: We measured iron status in 53 hemodialysis patients and studied the association with clinical, biochemical, and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) over 3 years. The blood pressure was controlled to below 140/90 mmHg by anti-hypertensive drugs., Results: Median and interquartile range of baseline baPWV, baPWV at 3 years, and ΔbaPWV (difference between 3-year baPWV and baseline baPWV) were following: 17.6 (14.8-18.9), 16.9 (15.3-19.9), and 0.2 (-1.2 to 2.7) m/s. At baseline, baPWV was positively correlated with age, serum ferritin, and systolic blood pressure in univariate analysis. However, in multivariate analysis, only age and serum ferritin remained the significant determinants of baseline baPWV. After 3 years, ΔbaPWV was negatively correlated with age and positively with 3-year averaged serum ferritin in univariate analysis. Then, in multivariate analysis, only 3-year averaged serum ferritin was the important determinant of ΔbaPWV. ΔbaPWV was significantly increased in patients with 3-year averaged serum ferritin >500 ng/mL compared to patients with 3-year averaged serum ferritin ≤500 ng/mL., Conclusions: In hemodialysis patients, serum ferritin associates with the progressive arterial stiffness, especially when serum ferritin >500 ng/mL.

Background: Dialysis patients received intravenous iron to treat anemia and had high prevalence of peripheral artery disease (PAD). We hypothesized that high iron status might associate with the progression of PAD among hemodialysis patients. Therefore, we evaluated the relationship between iron status and progression of PAD., Methods: We measured iron status in 74 hemodialysis patients and studied the association with clinical, biochemical, and vascular parameters including progression of PAD measured by ankle-brachial index (ABI) over 3 years., Results: Mean baseline ABI was 1.03 ± 0.18. Mean ABI at 3 years was 0.95 ± 0.20. Mean ∆ABI (change in ABI after 3 years) was -0.08 ± 0.14. Serum ferritin was negatively correlated with baseline ABI (r = -0.232, p = 0.046). After 3 years, ∆ABI was negatively associated with 3-year averaged serum ferritin, phosphorus, and calcium-phosphate product (Ca × P) (r = -0.253, p = 0.029; r = -0.278, p = 0.016; r = -0.288, p = 0.013; respectively). After an adjusted model, 3-year averaged serum ferritin and Ca × P remained the significant determinants of ∆ABI (β = -0.234, p = 0.038; β = -0.271, p = 0.017; respectively). ∆ABI was significantly different between 3-year averaged serum ferritin level ≥600 and <600 ng/mL (p = 0.032)., Conclusions: In hemodialysis patients, high serum ferritin associates with progression of PAD, especially among those with high Ca x P level.

Background: Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma., Methods: We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis., Results: Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003)., Conclusion: Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy., (Copyright © 2015. Published by Elsevier Ltd.)

Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

Background: Heparin therapy may induce anti-platelet factor 4/heparin antibody (PF4-H Ab). Hemodialysis patients receive scheduled heparin and are at a risk of developing PF4-H Ab. Hemodialysis patients are also at a high risk of peripheral arterial disease (PAD). This study examines whether chronic PF4-H Ab exposure contributes to the progression of PAD measured by ankle brachial index (ABI) in hemodialysis patients., Materials and Methods: A total of 71 hemodialysis patients were enrolled, and the association between clinical, biochemical parameters and ABI after 3 years was studied. PF4-H Ab was evaluated by ELISA, and patients with titer ≥ 0.4 were taken as having PF4-H Ab., Results: Mean ABI was 1.04 ± 0.18 at baseline and 1.01 ± 0.17 after 3 years. Mean ΔABI (change in ABI after 3 years) was -0.04 ± 0.13. PF4-H Ab was positive in 26 patients. PF4-H Ab was not related to hemodialysis duration, DM history, smoking and age. Platelet count showed no correlation with PF4-H Ab. However, there was significance in ΔABI between PF4-H Ab-positive and PF4-H Ab-negative patients (p = 0.002). ΔABI was negatively correlated with PF4-H Ab and 3-year averaged serum Ca × P only (β = -0.378, p = 0.001; β = -0.263, p = 0.018, respectively). However, in PF4-H Ab-positive patients, the extent of ΔABI did not correlate with PF4-H Ab titers (r = -0.021, p = 0.921)., Conclusions: PF4-H Ab positivity, along with high levels of serum Ca × P, played a potential role in the progression of PAD over time.

B7-H4, a member of the inhibitory B7 family, can restrain T cell proliferation, activation, and cytokine secretion and may be involved in immune evasion in cancer patients. This study aimed to evaluate the diagnostic and prognostic value of pleural effusion levels of soluble B7-H4 (sB7-H4) in lung cancer patients with malignant pleural effusion (MPE). Pleural effusion samples were collected from 98 lung cancer patients with malignant effusion and from 60 patients with nonmalignant pleural effusion. Pleural effusion concentrations of sB7-H4 were measured using sandwich enzyme-linked immunosorbent assay. Malignant effusion exhibited higher sB7-H4 levels than those in nonmalignant effusion (P < 0.01). Lung cancer patients with pleural effusion sB7-H4 levels below 35.8 ng/ml had a longer overall survival than those with higher levels (P < 0.05). By multivariate analysis, pleural effusion sB7-H4 was an independent prognostic factor in patients with MPE. In conclusion, measurement of sB7-H4 might be a useful diagnostic and prognostic value for MPE patients.

Metastatic thymic carcinoma is an aggressive cancer that usually responds poorly to multimodal therapies. Although surgical resection is the preferred treatment for patients with advanced or metastatic disease, the clinical prognosis is typically poor. The present study describes a 63-year-old patient with thymic carcinoma who underwent a range of antitumor treatments, including surgical resection, post-operative radiotherapy and post-operative chemotherapy with several drugs, but ultimately responded to treatment with nab-paclitaxel (nab-P) and nedaplatin. Subsequent to six cycles of nab-P and nedaplatin, the lung and peritoneal metastases decreased in size and the pleural effusion was reduced. To the best of our knowledge, this is the first study to describe the response of an advanced thymic carcinoma to nab-P chemotherapy.

Background: There is a lack of consensus on how endoscopic ultrasound (EUS) guided pseudocyst drainage should be performed. This survey was carried out amongst members of the Asian Endoscopic Ultrasonography Group (AEG) to describe their practices in performing this procedure., Methods: This was an Asia wide multi-institutional survey amongst members of the Asian EUS group conducted between November and December 2013. The responses to a 19-question survey with regard to the practice of pseudocyst drainage were obtained., Results: In total, 19 endoscopists responded to the questionnaire and the mean (SD) number of procedures performed by each endoscopist was 87.95 (40); 42.2 % believed that prior endoscopic retrograde cholangiopancreatography (ERCP) is required and pancreatic duct stenting is indicated in patients with pancreatic duct disruption; 47.4 % used tapered catheters for track dilation and 42.1 % used the cystotome; 84.1 % would dilate the track up to 8 to 10 mm in size. Metallic stents were used by 10.5 % of the respondents and transcystic catheters were employed by 26.3 %. Those who were more experienced in the procedure tended to use the cystotome more frequently (P = 0.02) and removed the stents in less than 3 months after insertion (P = 0.011)., Conclusion: This was the first Asia wide survey in the practice of pseudocyst drainage. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need for establishment of a consensus for safe practices.

Aim: The aim of this study was to evaluate the diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) and carcinoembryonic antigen (CEA) in lung cancer patients with malignant pleural effusion (MPE) and benign pleural effusion (BPE)., Methods: Pleural effusion samples from 118 patients were classified on the basis of diagnosis as MPE (n=60) and BPE (n=58). The concentration of sRCAS1 was determined by enzyme-linked immunosorbent assay. The CEA levels were also determined in all patients., Results: Of 60 MPE patients, 50 had sRCAS1>9.7 U/mL and 54 had CEA>5.5 ng/mL. The concentration of both sRCAS1 and CEA in MPE was significantly higher compared with that in BPE (P<0.01 in both cases). With a cutoff point of 9.7 U/mL, sRCAS1 had a sensitivity of 83.3% and a specificity of 91.4% for differential diagnosis. The combined detection of sRCAS1 and CEA had a sensitivity of 98.3% and a specificity of 96.6% to distinguish MPE from BPE., Conclusion: The combined detection of sRCAS1 and CEA may be more valuable in the differential diagnosis between MPE and BPE., (© 2014 Wiley Publishing Asia Pty Ltd.)

Natural orifice transluminal endoscopic surgery (NOTES) is a novel surgical procedure during which abdominal operations can be performed with an endoscope passed through a natural orifice through an internal incision in the stomach, vagina, bladder or colon. NOTES is still evolving and many barriers stand on its way before it can gain acceptance in modern surgical practice. Effective access to the peritoneal cavity, closure techniques of the natural orifice access sites, development of a multitasking platform to accomplish procedures and support for special orientation are only a handful of its known limitations. Although the endoscope and conventional tools are useful for simple procedures, many important and complicated procedures are currently not possible due to limitation of degree of freedom (DOF) of the end effectors. We have developed a Master and Slave Transluminal Endoscopic Robot (MASTER) with nine degrees of freedom (DOF) in end effectors, which are long and flexible so as to enhance endoscopic procedures and NOTES. Using MASTER we have successfully performed endoscopic sub-mucosal dissections (ESD) to segmental hepatectomies in animal models. Thus, the MASTER robotic system shows great potential to perform new surgical procedures that are otherwise not possible with conventional endoscopic tools.

Ahead of Print article withdrawn by publisher. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and apoptosis in cells. The aim of this study was to explore the clinical significance and prognostic value of serum RCAS1 levels in patients with non-small cell lung cancer (NSCLC). Serum specimens from 97 patients with NSCLC, 30 healthy volunteers (HVs) and 60 patients with benign lung diseases (BLD) were collected. The concentrations of RCAS1 were measured by enzyme-linked immunosorbent assay (ELISA). Serum RCAS1 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). With a cutoff point of 19.8 U/mL, RCAS1 showed a good diagnostic performance for NSCLC. Univariate analysis revealed that NSCLC patients with elevated RCAS1 levels had significantly shorter overall survival times (p=0.013). By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (p=0.003). Measurement of RCAS1 might be a useful diagnostic and prognostic marker in NSCLC.

Human Cripto-1 (CR-1) plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of carcinomas, yet little is known about CR-1 in non-small cell lung cancer (NSCLC). The aims of this study were to detect CR-1 expression in NSCLC and to analyze its association with prognosis of NSCLC patients. The expression of CR-1 messenger RNA (mRNA) and protein in 35 cases of NSCLC and corresponding noncancerous tissue samples was examined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to detect the expression of CR-1 in 128 NSCLC tissues. The expression levels of CR-1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding noncancerous tissues (P < 0.001). A high level of CR-1 expression was correlated with poor tumor differentiation (P = 0.002), tumor-node-metastasis (TNM) stage (P = 0.004), and lymph node metastasis (P = 0.001). The results of the Kaplan-Meier analysis indicated that a high expression level of CR-1 resulted in a significantly poor prognosis of NSCLC patients. Multivariate Cox regression analysis revealed that CR-1 expression level was an independent prognostic parameter for the overall survival rate of NSCLC patients. Our data suggest that the high expression of CR-1 may play an important role in the progression of NSCLC, and CR-1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging., (© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and apoptosis in cells bearing the RCAS1 receptor. The aim of the study was to elucidate the diagnostic and prognostic value of RCAS1 levels in patients with non-small cell lung cancer., Methods: Sera collected from 30 healthy volunteers, 40 patients with benign lung diseases and 97 non-small cell lung cancer cases were subjected to RCAS1 ELISA, and relationships between serum RCAS1 and clinical characteristics were evaluated., Results: Serum RCAS1 levels were higher in the non-small cell lung cancer group than in the healthy volunteers and benign lung disease groups (P <0.001). With a cutoff level 19.8 U/ml, RCAS1 had a sensitivity of 87.6%, a specificity of 82.5% and an accuracy of 86.1% for non-small cell lung cancer. Univariate analysis revealed that non-small cell lung cancer patients with elevated RCAS1 levels had significantly shorter overall survival (P = 0.042) than the other two groups. By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (P = 0.003)., Conclusions: Assessment of serum RCAS1 levels could be considered as a diagnostic and prognostic marker in non-small cell lung cancer.

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95% CI 0.99-1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95% CI 0.96-1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger's test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers.

The aim of this study was to explore the diagnostic and prognostic value of serum human kallikrein-related peptidases 11 (KLK11) level in non-small cell lung cancer (NSCLC). Serum specimens from 138 patients with NSCLC and 40 healthy controls were collected. The concentration of KLK11 was measured by enzyme-linked immunosorbent assay (ELISA). The concentration of KLK11 in NSCLC was significantly higher compared to that in the controls (P<0.01). The serum KLK11 levels decreased with stage, presence of lymph node, and distant metastases, regardless of histology, age, and sex. With a cutoff point of 1.05 ng/ml, KLK11 showed a good diagnostic performance for NSCLC. Univariate analysis revealed that NSCLC patients with serum high KLK11 had a longer overall survival (OS) and progression-free survival (PFS) than those with low KLK11 (HR of 0.36, P=0.002; HR of 0.46, P=0.009). Cox multivariate analysis indicated that KLK11 was an independent prognostic indicator of PFS and OS (HR of 0.53, P=0.042; HR of 0.48, P=0.037). Kaplan-Meier survival curves further confirmed that patients with high KLK11 have longer PFS and OS (P=0.003 and P=0.018, respectively). In conclusion, the measurement of KLK11 might be a useful diagnostic and prognostic test for NSCLC patients.

This study was to explore the association between the serum YKL-40 level and the clinical characteristics, the response to chemotherapy and prognosis in small cell lung cancer (SCLC). Serum YKL-40 levels were detected and compared in 120 patients with SCLC pre- and post-chemotherapy, and in 40 healthy controls. Receiver operating characteristics (ROC) curves were adopted for diagnosis and calculation of area under ROC curve in SCLC. The Kaplan-Meier method, univariate and multivariate Cox regression analysis were used to analyze the correlation between pre-chemotherapy serum YKL-40 levels and progression-free survival (PFS) and overall survival (OS). The pre-chemotherapy serum YKL-40 levels were significantly higher than those of the controls (p<0.001). The post-chemotherapy serum YKL-40 levels in the SCLC cases were lower than pre-chemotherapy serum YKL-40 levels in these cases (p = 0.026). The patients with high serum YKL-40 showed a poorer response to chemotherapy than those patients with low serumYKL-40 (p = 0.031). Univariate analysis revealed that SCLC patients with high serum YKL-40 had a shorter PFS and OS than those with low serum YKL-40 (HR of 1.74, p = 0.033; HR of 1.33, p = 0.001). Cox multivariate analysis indicated that YKL-40 was an independent prognostic indicator of PFS and OS (HR of 1.12, p = 0.029; HR of 1.84, p = 0.025). Kaplan-Meier survival curves further confirmed that patients with low serum YKL-40 have longer PFS and OS (p = 0.016 and p = 0.041, respectively). These results suggest that YKL-40 is a potential prognostic marker of chemotherapy response in SCLC.

Previous studies have shown that the isoplanatic angle (θ₀) can be measured by using plane-wave scintillation. The problem of measuring the isoplanatic angle in a finite distance using spherical-wave scintillation is considered in this Letter. Based on theoretical analysis and numerical evaluation, we found that by selecting suitable aperture size and aperture separations, the isoplanatic angle can be estimated through spherical-wave scintillation and covariance of irradiance in three received apertures using a point source. The error of θ₀ measured by this method is less than 6% in typical turbulence models.

Interleukin 17 (IL-17) has been found to be increased in some human cancers; however, the possible implication of IL-17 in regulating antitumor responses in lung cancer patients with malignant pleural effusions (MPE) remains to be elucidated. This study aimed to investigate the diagnostic value of pleural IL-17 and carcinoembryonic antigen (CEA) in MPE and benign pleural effusions (BPE). Pleural effusion samples from 108 patients were classified on the basis of diagnosis as MPE (n = 56) and BPE (n = 52). The concentration of IL-17 was determined by enzyme-linked immunosorbent assay (ELISA). The CEA levels were also determined in all patients. A significant difference was observed in the levels of CEA (P < 0.01) between MPE and BPE. The concentration of IL-17 in MPE was significantly higher compared to that in BPE (P < 0.01). With a cutoff point of 15.7 pg/ml, IL-17 had a sensitivity of 76.8 % and a specificity of 80.8 % for differential diagnosis. The combined detection of IL-17 and CEA had a sensitivity of 96.4 % and a specificity of 92.3 % to distinguish MPE from BPE. The combined detection of IL-17 and CEA may be more valuable in the differential diagnosis between MPE and BPE.

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent., Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis., Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, <0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival., Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

The aim of this study was to explore the diagnostic value of levels of the serum-soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) expressed in lung cancer patients. Enzyme-linked immunosorbent assay was performed to detect serum sRCAS1 levels in 138 patients with lung cancers of various types and in 40 healthy controls. Our results showed that the patients with lung cancer had higher serum sRCAS1 levels than the controls. As disease stages progressed in lung cancer, serum sRCAS1 levels increased; patients with lymph node and distant metastases had higher levels than those without metastases, regardless of histology, age, and gender. At a cutoff value of 19.2 U/ml, sRCAS1 was 91.3% sensitive and 72.5% specific for lung cancer. In conclusion, these results suggest that sRCAS1 levels could have a clinical value for the diagnosis and management of lung cancer and could be used as a new tumor marker of lung cancer.

The genetic polymorphism of the CYP1A1 exon7 (rs1048943) gene is thought to have a significant effect on lung cancer risk, but the results are inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 45 case-control studies, involving 19,689 subjects were included. A significantly increased lung cancer risk was associated with two exon7 genotype variants (for Val/Val vs Ile/Ile: odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.10-1.43; for (Ile/Val + Val/Val) vs Ile/Ile: OR = 1.16, 95% CI = 1.08-1.24) in the overall population. In the stratified analysis by ethnicity, gender, and smoking status, a significant association was found in Asians, Caucasians, and the female population, not the male population. Additionally, a significant association was found in the smoker population, not in the nonsmoker population. This meta-analysis suggests that the exon7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between CYP1A1 exon7 polymorphisms and smoking, but these associations vary in different genders of the case and control populations.

Background: Various studies examined the relationship between p53 mutation with the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results., Methods: Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between p53 mutation and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed., Results: We performed a meta-analysis of 9 studies that evaluated the correlation between p53 mutation and survival in patients with HCC. Combined hazard ratios suggested that p53 mutation had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.46, 95% confidence interval (CI): 1.15-1.76], and disease free survival (DFS) (HR =2.57, 95% CI: 1.46-3.68) in patients with HCC. The significant heterogeneity (P=0.035) was observed among 8 studies for OS, however no significant heterogeneity (P=0.597) was observed among 5 studies for DFS., Conclusions: p53 mutation indicates a poor prognosis for patients with hepatocellular carcinoma.

Iron is essential for pathogen survival, virulence, and colonization. Feo is suggested to function as the ferrous iron (Fe(2+)) transporter. The enterobacterial Feo system is composed of 3 proteins: FeoB is the indispensable component and is a large membrane protein likely to function as a permease; FeoA is a small Src homology 3 (SH3) domain protein that interacts with FeoB; FeoC is a winged-helix protein containing 4 conserved Cys residues in a sequence suitable for harboring a putative iron-sulfur (Fe-S) cluster. The presence of an iron-sulfur cluster on FeoC has never been shown experimentally. We report that under anaerobic conditions, the recombinant Klebsiella pneumoniae FeoC (KpFeoC) exhibited hyperfine-shifted nuclear magnetic resonance (NMR) and a UV-visible (UV-Vis) absorbance spectrum characteristic of a paramagnetic center. The electron paramagnetic resonance (EPR) and extended X-ray absorption fine structure (EXAFS) results were consistent only with the [4Fe-4S] clusters. Substituting the cysteinyl sulfur with oxygen resulted in significantly reduced cluster stability, establishing the roles of these cysteines as the ligands for the Fe-S cluster. When exposed to oxygen, the [4Fe-4S] cluster degraded to [3Fe-4S] and eventually disappeared. We propose that KpFeoC may regulate the function of the Feo transporter through the oxygen- or iron-sensitive coordination of the Fe-S cluster.

Background: Hepatocellular carcinoma (HCC) is a highly vascular tumor that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC, but yielded conflicting results., Methods: Electronic databases updated to June 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between serum VEGF level and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed., Results: We performed a meta-analysis of 11 studies that evaluated the correlation between serum VEGF level and survival in patients with HCC. Combined hazard ratios suggested that serum VEGF level had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.88, 95% confidence interval (CI): 1.46-2.30], and disease free survival (DFS) (HR=2.27, 95% CI: 1.55-2.98) in patients with HCC. No significant heterogeneity was observed among all studies., Conclusions: Serum high VEGF level indicates a poor prognosis for patients with hepatocellular carcinoma.

Background: Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results., Methods: Electronic databases updated to June 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed., Results: We performed a meta-analysis of 14 studies that evaluated the correlation between VEGF overexpression and survival in patients with HCC. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.42, 95% confidence interval (CI): 1.42-1.7], but not disease free survival (DFS) (HR=1.13, 95% CI: 0.89-1.38) in patients with HCC. No significant heterogeneity (P=0.949) was observed among 9 studies for OS, however significant heterogeneity (P=0.008) was observed among 11 studies for DFS., Conclusions: VEGF overexpression indicates a poor prognosis for patients with HCC.