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Anticoagulation response to warfarin during the initial stage of therapy varies among individuals. In this study, we aimed to combine pharmacometabolomic and pharmacogenetic data to predict interindividual variation in warfarin response, and, on this basis, suggest an initial daily dose range. The baseline metabolic profiles, genotypes, and clinical information of 160 patients with heart valve disease served as the variables of the function of the last international normalized ratio measured before a patient's discharge (INRday7 ) to screen for potential biomarkers. The partial least-squares model showed that two baseline metabolites (uridine and guanosine), one single-nucleotide variation (VKORC1), and four clinical parameters (weight, creatinine level, amiodarone usage, and initial daily dose) had good predictive power for INRday7 (R2 = 0.753 for the training set, 0.643 for the test set). With these biomarkers, a machine learning algorithm (two-dimensional linear discriminant analysis-multinomial logit model) was used to predict the subgroups with extremely warfarin-sensitive or less warfarin-sensitive patients with a prediction accuracy of 91% for the training set and 90% for the test set, indicating that individual responses to warfarin could be effectively predicted. Based on this model, we have successfully designed an algorithm,"IniWarD," for predicting an effective dose range in the initial 7-day warfarin therapy. The results indicate that the daily dose range suggested by the IniWarD system is more appropriate than that of the conventional genotype-based method, and the risk of bleeding or thrombus due to warfarin could thus be avoided.

Background Extracorporeal membrane oxygenation (ECMO) has evolved considerably over the past two decades and has been gradually utilized in severe trauma. However, the indications for the use of ECMO in trauma remain uncertain and the clinical outcomes are different. We performed a systematic review to provide an overall estimate of the current performance of ECMO in the treatment of trauma patients. Materials and methods We searched PubMed and MEDLINE databases up to the end of December 2019 for studies on ECMO in trauma. The PRISMA statement was followed. Data on demographics of the patient, mechanism of injury, injury severity scores (ISS), details of ECMO strategies, and clinical outcome were extracted. Results A total of 58 articles (19 retrospective reports and 39 case reports) were deemed eligible and included. In total, 548 patients received ECMO treatment for severe trauma (adult 517; children 31; mean age of adults 34.9 ± 12.3 years). Blunt trauma (85.4%) was the primary injury mechanism, and 128 patients had traumatic brain injury (TBI). The mean ISS was 38.1 ± 15.0. A total of 71.3% of patients were initially treated with VV ECMO, and 24.5% were placed on VA ECMO. The median time on ECMO was 9.6 days, and the median time to ECMO was 5.7 days. A total of 60% of patients received initially heparin anticoagulation. Bleeding (22.9%) and thrombosis (19%) were the most common complications. Ischemia of the lower extremities occurred in 9 patients. The overall hospital mortality was 30.3%. Conclusions ECMO has been gradually utilized in a lifesaving capacity in severe trauma patients, and the feasibility and advantages of this technique are becoming widely accepted. The safety and effectiveness of ECMO in trauma require further study. Several problems with ECMO in trauma, including the role of VA-ECMO, the time to institute ECMO, and the anticoagulation strategy remain controversial and must be solved in future studies.

3D printing in adult cardiac and vascular surgery has been evaluated over the last 10 years, and all of the available literature reports benefits from the use of 3D models. In the present study, we analyzed the current applications of 3D printing for adult cardiovascular disease treated with surgical or catheter-based interventions, including the clinical medical simulation of physiological or pathology conducted with 3D printing in this field. A search of PubMed and MEDLINE databases were supplemented by searching through bibliographies of key articles. Thereafter, data on demographic, clinical scenarios and application, imaging modality, purposes of using with 3D printing, outcomes and follow-up were extracted. A total of 43 articles were deemed eligible and included. 296 patients (mean age: 65.4±14.2 years; male, 58.2%) received 3D printing for cardiac and vascular surgery or conditions [percutaneous left atrial appendage occlusion (LAAO), TAVR, mitral valve disease, aortic valve replacement, coronary artery abnormality, HOCM, aortic aneurysm and aortic dissection, Kommerell's diverticulum, primary cardiac tumor and ventricular aneurysm]. Eight papers reported the utility of 3D printing in the medical simulator and training fields. Most studies were conducted starting in 2014. Twenty-six was case report. The major scenario used with 3D printing technology was LAAO (50.3%) and followed by TAVR (17.6%). CT and echocardiography were two main imaging techniques that were used to generate 3D-printed heart models. All studies showed that 3D-printed models were helpful for preoperative planning, orientation, and medical teaching. The important finding is that 3D printing provides a unique patient-specific method to assess complex anatomy and is helpful for intraoperative orientation, decision-making, creating functional models, and teaching adult cardiac and vascular surgery, including catheter-based heart surgery.

Infantile hemangioma is one of the most common vascular tumors, which might result in morbidity and mortality without timely intervention. Propranolol is currently the first-line therapy for hemangiomas, but its potential side effects and high frequency of administration make it urgent to develop a suitable drug delivery system for propranolol. In the present study, we formulated a propranolol delivery system based on mesoporous silica nanoparticles (PRN@MSN) and investigated the interplay between autophagic activities mediated by nanoparticles and improved therapeutic efficacy of PRN@MSN. The results showed that PRN@MSN nanoparticles exhibited higher cytotoxicity compared with free propranolol in vitro and in vivo, which could induce excessive autophagosome accumulation through increased autophagosome formation and impaired autophagic degradation. Inhibition of autophagy in the early stage could attenuate the cytotoxicity of PRN@MSN. ROS generation was essential for nanoparticle-mediated autophagy and cytotoxicity, and PRN@MSN-induced autophagy dysfunction could enhance endoplasmic reticulum (ER) stress in hemangioma stem cells. Our study revealed a promising PRN delivery system based on a mesoporous silica nanoplatform that could induce autophagy dysfunction with excessive autophagosome accumulation to promote the therapeutic efficacy of PRN therapy. PRN@MSN drug delivery system combined with autophagy modulation may act as a promising treatment pattern in the treatment of hemangiomas.

Hypoxia plays an important role in cancer progression, which is a characteristic feature of the tumor micro-environment and reflects the invasiveness of tumor cells. Nitroreductase (NTR) is overexpressed in hypoxic tumors, which making it an efficient target for detecting the hypoxic state in tumor. In this work, a new type of nitro-based fluorescent probe, named HNT-NTR, has been proposed, HNT-NTR could detect specifically and rapidly the NTR degree, which reflects the level of hypoxia in bidimensional (2D) tumor cells, three-dimensional (3D) tumor spheres and even the real tumors in vivo without biological toxicity. Most importantly, according to the research, HNT-NTR even could distinguish tumor cells from other normal cells in vivo and reflect the invasiveness of tumor cells by the near-infrared fluorescence intensity, which provides a new way of clinical pathologic diagnosis. All in all, HNT-NTR not only is proven to be an ideal probe for detecting solid tumors in vivo, but also has great potential to distinguish if cells are benign or malignant and even guide therapeutic applications in the clinic.

Wound healing is an important and complicated process that includes four highly integrated and overlapping phases, haemostasis, inflammation, proliferation and tissue remodelling. Nerve growth factor (NGF) was the first member of a family of neurotrophic factors to be discovered, and is an essential neurotrophic factor for the development and maintenance of the central and peripheral nervous systems. Several studies have proposed that NGF and its receptors, tropomyosin-related kinase receptor 1 and NGF receptor, are involved in the wound healing process, and are important components of the healing of several wounds both in vivo and in vitro. Topical application of NGF significantly promotes the healing of different types of wounds, including diabetic foot ulcers, pressure ulcers and corneal wounds. The present review summarizes the status of NGF and its receptors in current literature, and discusses data obtained in the last few years on the healing action of NGF in cutaneous, corneal and oral wounds.

Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

Angiogenesis is a core hallmark of advanced cancers, especially in lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of lncRNAs in tumor angiogenesis remain largely unknown. Here we found that linc00665 depletion could markedly depressed proliferation and capillary tube formation of HUVECs in vitro. Mechanistically, linc00665 directly interacted with YB-1 protein, enhanced its stability through inhibiting ubiquitination-dependent proteolysis and stimulated its nuclear translocation in LUAD cells. The accumulated nuclear YB-1 activated expression of ANGPT4, ANGPTL3 and VEGFA by binding to their promoters, contributing to tumor-related angiogenesis in vitro and in vivo. Collectively, we conclude that linc00665 induces tumor-related angiogenesis in LUAD by directly interacting with YB-1 and activating YB-1-ANGPT4/ANGPTL3/VEGFA axis, which provides promising anti-angiogenic targets for cancer therapy.

Objectives Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients with heart valve disease. Our aim was to summarize our experience and evaluate the efficacy and safety of the Cox maze III procedure combined with valve surgery in patients with AF. Methods A retrospective, observational analysis was performed for all consecutive patients underwent maze III procedure combined with valve surgery between October 2015 and June 2019. In this trial, we used a monopolar radiofrequency (RF) ablation in addition to cut and sew technique to treat AF. Results 66 patients (37 female, 56.1%) with persistent or long-lasting persistent AF associated with valve disease were identified. The mean age was 54.2 ± 8.4 years (range, 30 to 73 years). Overall hospital mortality was 3.0%. The duration of cardiopulmonary bypass and aortic cross clamping was 175.4 ± 32.9 and 115.6 ± 22.8 min respectively. The first 24 h drainage was 488.6 ± 293.3 ml. The postoperative hospital stay was 14.8 ± 8.3 days. The postoperative incidence of permanent pacemaker implantation, reoperation for bleeding, renal failure required hemodialysis, and stroke was 4.5, 1.5, 4.5% and 0 respectively. The frequency of sinus rhythm was 91.7, 93.1, 94.7, 93.3 and 89.5% at 1, 3, 6, 12, and 24 months respectively. Conclusions The Cox-Maze III procedure is safe in the surgical treatment of AF associated with valve disease, and efficacious for sinus rhythm maintenance, with low morbidity and mortality.

Objective. Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. Methods. We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60 mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Results. Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Conclusion. Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1α/VEGF signaling-related angiogenesis.

This study is aimed at determining the optimal sinus augmentation approach considering the poor bone condition in the zone of atrophic posterior maxilla. A series of simplified maxillary segment models varying in residual bone height (RBH) and bone quality were established. A 10 mm standard implant combined with two types of maxillary sinus augmentation methods was applied with the RBH, which was less than 10 mm in the maxilla. The maximal equivalent von Mises (EQV) stress in residual bone was evaluated. Bone quality had an enormous impact on the stress magnitude of supporting bone. Applying sinus augmentation combined with grafts was suitable for stress distribution, and high-stiffness graft performed better than low-stiffness one. For 7 mm and 5 mm atrophic maxilla, nongrafted maxillary sinus augmentation was feasible in D3 bone. Poor bone quality was a negative factor for the implant in the region of atrophic posterior maxilla, which could be improved by grafts. Meanwhile, the choice of maxillary sinus augmentation approaches should be determined by the RBH and quality.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. For better diagnosis and precise resection of HNSCC, Fluorescent probe has been developed as an ideal tool to visualize tumor sites and to detect biological molecules. However, the targeting strategies of small molecular probes are limited. We designed probe RB-PN (Rhodamine biotin-peroxynitrite) with both sodium-dependent multivitamin transporter (SMVT)-targetable and peroxynitrite (ONOO−)-activatable tumor-targeting strategies. It can detect ONOO− with high specificity and selectivity, and rapid response. Besides, it exhibits prominent imaging abilities with enhanced accumulation by SMVT-transportation. The remarkable sensitivity, selectivity, turn-on signal change and rapid responsive time have been identified. We evidenced the dual-targeting strategy, and applied it in tumor visualization and ONOO− detection both in HNSCC cells and in vivo. We also identified the potential application of it in cytokine therapy using 3D micro-spheroid models. We expect RB-PN with a dual-targeting strategy could be conducive to the diagnosis of tumor pre-operatively or even intra-operatively.

In this work, a microporous and high surface area carbon material with excellent electron conductivity is synthesized through carbonizing and activation processes using waste shaddock wadding. Because of the unique multi-hole, thin sheets cluster and irregular wrinkled surface coexisting structure, the shaddock wadding carbon-sulfur (SWD-S) composite can be used as a kind of cathode material for rechargeable lithium-sulfur batteries by loading element sulfur into the shaddock wadding activated carbon via simple heat treatments. Because of the high specific surface area of SWD (1637.3 m 2 g −1 ), the SWD-S composite has a sulfur content about 73.7 wt%, and delivers a high initial discharge capacity of 1050 mAh g −1 at a rate of 0.2C. Moreover, SWD-S composite exhibits a good rate capacity and excellent cycle ability. Over 200 cycles it achieves with a high columbic efficiency around 95%. After 200 cycles at 0.2C, it still remains a capacity of 599 mAh g −1 .

Malignant melanoma, developing from melanocytes, is a kind of high metastatic tumor. Circulating melanoma cells, as a marker for metastasis development, are found in blood or lymphatic system at the early stage. Thus, quantitative detection of circulating melanoma cells has great significance to diagnose carcinoma and monitor tumor metastasis. In contrast to in vitro detection methods and in vivo fluorescence-based flow cytometry (IVFC), the in vivo photoacoustic flow cytometry (PAFC) utilizes melanoma cells’ predominant optical absorption in the near-infrared range over other absorbers to receive the photoacoustic (PA) signals without fluorescent dye labeling in a non-invasive way. The sensitivity of the PAFC system was verified by in vitro and in vivo experiments. Besides, we solves the technical problem that blood vessels cannot be positioned in the process of in vivo detection by designing the laser signal positioning navigation system using frequency doubling technique. PAFC provides a new tool for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs) and has strong practicality and favorable clinical prospects.

Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single-layer (S-MoS2), few-layer (F-MoS2), and multi-layer (M-MoS2) nanosheets by the albumin-assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M-MoS2 to S-MoS2 can both significantly enhance the near-infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S-MoS2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S-MoS2 to both U87 subcutaneous and orthotopic tumor-bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S-MoS2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.

Potassium hydroxide (KOH) activated Super P (Ksp) was adopted to prepare Ksp/S composite by chitosan assisted chemical synthesis approach. The Ksp/S was further heat treated at 159 °C and then coated by polyaniline (PANI) to fabricate Ksp/S-159 and Ksp/S-159/PANI composites, respectively. The heat treated binary sulfur/carbon and PANI coated ternary sulfur complex showed enhanced cycle performance and rate capability. However, the electrochemical behavior of Ksp/S-159 and Ksp/S-159/PANI can be greatly affected by the discharge current. The Ksp/S-159/PANI composite delivers an initial discharge capacity of 1202.3 mAh g −1 and keeps 954 mAh g −1 after 100cycles at 0.5 mA cm −2 (0.31C). The Ksp/S-159 presented a maximum capacity up to 892.5 mA h g −1 at 2 ma cm −2 (1.26C) and retained about 409.2 mA h g −1 after 500 cycles. The PANI coated ternary sulfur complex shows good electrochemical performance at low discharge current while the heat treated sulfur/carbon shows good rate capability at high discharge current. The different electrochemical behavior is fully discussed to illustrate the complex Li-S discharging process.

BACKGROUND This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD. MATERIAL AND METHODS Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD. RESULTS SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors. CONCLUSIONS Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.

Objectives Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia-induced autophagy was up-regulated in the progression of SACC. Materials and methods We performed differentially expressed gene analysis and pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF-1ɑ and MAP1LC3B was analyzed in the paraffin-embedded specimens by immunohistochemical method and in the hypoxic SACC-LM cells by immunofluorescence. TEM microscopy was also performed to observe the formation of autophagosomes in SACC tissue and the hypoxic SACC-LM cells. Results The autophagy pathway was up-regulated in SACC datasets, and five genes including MAP1LC3B were positively correlated with HIF-1ɑ. Immunohistochemistry results showed that autophagy was activated and the expression of HIF-1ɑ and MAP1LC3B was positively correlated in SACC specimens. In hypoxic SACC-LM cells, we also identified the up-regulation of autophagy and the close correlation between HIF-1ɑ and MAP1LC3B expression. Autophagosomes were observed both in the tissue and the hypoxic SACC-LM cells by TEM microscopy. Conclusions Our study showed that autophagy is up-regulated in dataset, SACC tissue, and hypoxic cell line; hypoxia-induced autophagy in SACC might play a vital role in the development of SACC.

Lymph node metastasis (LNM) is one of the major causes of cancer-associated morbidity and mortality in patients with lung cancer following radical pulmonary carcinoma resection. The present study aimed to investigate the relationship between the expression of collagen and calcium-binding epidermal growth factor domain-containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of lung cancer. The present study included 40 patients with lung cancer that underwent pulmonary carcinoma resection, including 10 patients with LNM, and 10 control patients who underwent pulmonary bullae resection. CCBE1 and LYVE1 expression was assessed in samples from normal and tumor tissue using polymerase chain reaction, western blot analysis and immunohistochemistry. CCBE1 expression appeared to be decreased in lung tumor tissue and further downregulated in samples from patients with LNM, and was revealed to be correlated with poor clinical outcome. Conversely, LYVE1 expression appeared to be upregulated in lung cancer tissue. In conclusion, the present results suggested that CCBE1 and LYVE1 may have potential as biomarkers for the identification of lung cancer patients at a high risk of LNM.

Autophagy is a major intracellular pathway involving in the degradation and recycling of cytosolic material, including organelles, proteins, and ribosomes. Autophagy is commonly active in tumor cells and could be induced by stress conditions such as hypoxia, nutrient depletion and anticancer therapy. Increasing evidence supports the role of autophagy in modulating cancer behavior in head and neck squamous cell carcinoma (HNSCC). Despite recent advances in surgery combined with chemotherapy and radiotherapy, the survival rate of patients with HNSCC has not been improved substantially. To adapt to the hostile microenvironment induced by stress condition including hypoxia and anticancer therapy, more biological changes such as autophagy are induced in tumor cells contributing to their malignant and aggressive behavior. In the present review, we summarized recent findings on the molecules involved in the autophagy induced by hypoxia and anticancer therapy and basic mechanisms of autophagy, and focused on elucidating the role of autophagy in tumor progression of HNSCC. Some novel studies on the relationships between mircoRNA and autophagy were also discussed in this review. A better understanding of this knowledge may provide new ideas and targets for effective prevention and treatment in HNSCC.

C-X-C chemokine receptor 4 and Notch1 have been shown to play oncogenic role individually. This study aimed to determine the combinatorial role of C-X-C chemokine receptor 4 and Notch1 in lung adenocarcinoma. Expression of C-X-C chemokine receptor 4 and Notch1 was detected in resected tumor samples from 185 patients with lung adenocarcinoma at stage I–IIIa by immunohistochemistry. Correlations of their immunoscores with clinicopathological characteristics and disease-specific survival were retrospectively investigated. A three-dimensional capillary-like sprouting model was established to assess the effects of C-X-C chemokine receptor 4 and Notch1 on angiogenesis in vitro. The results revealed that expression of C-X-C chemokine receptor 4 and Notch1 was elevated in lung adenocarcinoma tissues. The high co-expression of C-X-C chemokine receptor 4 and Notch1 was significantly correlated with tumor size, tumor status, nodal status, tumor stage, and lymphovascular invasion, as well as decreased disease-specific survival. Multivariate analysis showed that lymphovascular invasion (hazard ratio: 0.205, 95% confidence interval: 0.086–0.491, p < 0.0001) and co-expression of C-X-C chemokine receptor 4 and Notch1 (hazard ratio: 0.293, 95% confidence interval: 0.168–0.510, p < 0.0001) were independent indicators of poor prognosis in lung adenocarcinoma. Furthermore, Notch1 enhanced the effects of C-X-C chemokine receptor 4 to promote angiogenesis by regulating Flt1 and Flt4 in vitro. In conclusion, co-expression of C-X-C chemokine receptor 4 and Notch1 is associated with tumor progression and lymphovascular invasion and is an independent indicator of poor survival in lung adenocarcinoma. In lung adenocarcinoma patients with high C-X-C chemokine receptor 4 and Notch1 expression, simultaneous inhibition of both factors might be an effective treatment strategy.

Background Surgical treatment for patients with esophageal carcinoma that invades the aorta locally (stage IIIc) remains a considerable challenge. This study aimed to introduce radical esophagectomy combined with off-pump descending aorta replacement in these patients and to assess the effects on both short-term and long-term outcomes. Methods The clinical data of 47 patients who had esophageal carcinoma invading the descending aorta and who underwent radical esophagectomy combined with off-pump aortic replacement between January 2001 and March 2012 in Jinling Hospital were retrospectively reviewed. The intraoperative, early postoperative, and follow-up results were analyzed. Results Overall, 80.9% and 19.1% of the patients had histopathologically confirmed aortic tunica adventitia invasion and media invasion, respectively. All patients received complete resection (R0) with an average intraoperative blood loss of 227.6 ± 63.3 mL. The mean operative time and aortic cross-clamping time were 4.9 ± 1.3 hours and 17.0 ± 3.2 minutes, respectively. Complications were observed in 59.6% of patients, with no hospital mortality, and all patients resumed an oral diet 1 month after the procedure. The overall 1-, 3-, and 5-year survival rates were 80.9%, 44.7%, and 21.3%, respectively, with a median survival time of 33.6 months. Conclusions In patients with esophageal carcinoma invading the aorta, it is feasible and safe to perform radical esophagectomy combined with off-pump descending aorta replacement to improve nutritional status and achieve satisfactory survival.

Oxidative stress is becoming increasingly linked to the pathogenesis of abdominal aortic aneurysms (AAAs). The antioxidant activity of flavonoids has attracted attention for their possible role in the prevention of cardiovascular diseases. The purpose of this study was to determine whether an antioxidant mechanism is involved in the aneurysm formation inhibitory effect afforded by quercetin. Male C57/BL6 mice received quercetin continuously from 2 weeks prior to and 6 weeks following the AAA induction with extraluminal CaCl2. Quercetin treatment decreased AAA incidence and inhibited the reactive oxygen species generation, nitrotyrosine formation and lipid peroxidation production in the aortic tissue during AAA development. In addition, quercetin‑treated mice exhibited significantly lower expression of the p47phox subunit of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, as well as coordinated downregulation of manganese‑superoxide dismutase activities and glutathione peroxidase (GPx)‑1 and GPx‑3 expression. Quercetin also blunted the expression of c‑Jun N‑terminal kinase (JNK) and phospho‑JNK and, in addition, diminished activation of the activator protein (AP)‑1 transcription factor. Gelatin zymography showed that quercetin eliminated matrix metalloproteinase (MMP)‑2 and MMP‑9 activation during AAA formation. In conclusion, the inhibitory effects of quercetin on oxidative stress and MMP activation, through modulation of JNK/AP‑1 signaling, may partly account for its benefit in CaCl2‑induced AAA.

Previous studies have shown that lipopolysaccharide (LPS) induces acute lung injury (ALI), and that endothelial progenitor cells (EPCs) participate in tissue repair. Therefore, in this study it was hypothesized that LPS influences the number and function of EPCs directly. In order to investigate this, an in vitro study was performed using EPCs. EPCs were cultured for seven days (early EPCs), and then treated with increasing concentrations of LPS (10 pg/ml, 100 pg/ml, 1 ng/ml, 10 ng/ml and 100 ng/ml) for 4, 8, 12, and 24 h. The proliferation, senescence and adhesion of EPCs was then assessed. Alongside this an in vivo study was also performed. Mice were administered LPS (2.5 mg/kg) via the trachea. After 4, 8, 12, and 24 h, EPCs were harvested and cultured for seven days, and the proliferation, senescence and adhesion of the EPCs were examined. The results showed that the rate of adhesion and senescence of EPCs decreased in vitro when treated with 10 and 100 ng/ml LPS. The adhesion and senescence rate also decreased after 12 and 24 h in vivo. Proliferation, however, was increased in vitro following treatment with 10 and 100 ng/ml LPS, but proliferation in vivo decreased after 8 and 12 h. The effects of LPS on EPCs were distinct in vivo and in vitro. In vitro, cells were sensitive to 100 ng/ml LPS. In the course of ALI induced by LPS, the proliferation and adhesion activity of the EPCs was activated in 8 h and then gradually decreased with time.

Background Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths. It is therefore urgent that we identify new molecular targets to help cure NSCLC patients. Here, we identified ZIC5 as a potential novel oncogene. Methods We detected the expression of ZIC5 in tumor and normal tissues of NSCLC patients using quantitative real-time PCR and explored its clinical appearance. We then knocked down ZIC5 to observe changes in NSCLC cell proliferation and metastasis. Nude mouse xenograft models were established to measure ZIC5's function in vivo . Results Our results revealed that ZIC5 was expressed at dramatically higher levels in NSCLC tumor tissues than in normal tissues. High levels of ZIC5 expression were associated with a higher primary tumor grade. ZIC5 expression was significantly inhibited by small interfering RNA. After silencing ZIC5, the metastatic capacity of NSCLC cells was clearly lower. Knocking down ZIC5 significantly inhibited the proliferation of NSCLC cells, causing the cell cycle to be arrested in G2 phase. Xenograft tumor models showed that knocking down ZIC5 also inhibited tumor growth in vivo . Q-PCR and western blot analysis revealed that ZIC5 expression was closely associated with CCNB1 and CDK1 complex expression, while other cell cycle-related genes showed no significant correlation with ZIC5. Conclusions Our experiment show that ZIC5 is highly upregulated in NSCLC tumor tissues and suggest that ZIC5 may act as an oncogene by influencing CCNB1 and CDK1 complex expression. ZIC5 may therefore be a potential biomarker and therapeutic target for NSCLC patients.

Acute lung injury is a frequent complication after cardiopulmonary bypass (CPB). Recent studies have reported that NF-κB plays an important role in the pathogenesis of post-CPB pulmonary dysfunction. Several signaling pathways, including the TLR4 pathway, induce NF-κB leading to an inflammatory response. We designed this study to determine whether or not curcumin inhibits TLR4 and MyD88 protein levels and ameliorates lung inflammatory injury in a rat CPB model.Sprague-Dawley rats were randomly divided into the following five groups (n = 12): sham; control (CPB); vehicle; low-dose curcumin (L-Cur); and high-dose curcumin (H-Cur). The percutaneous beating heart CPB model of rat was established. Animals were pretreated with a single intraperitoneal injection of vehicle, L-Cur (50 mg/kg), or H-Cur (200 mg/kg) 2 h prior to CPB. Blood were sampled at various time points, then lung tissues and bronchoalveolar lavage fluid were harvested 24 h after CPB.CPB induced a marked increase in the concentrations of interleukin-8, tumor necrosis factor-α, and matrix metalloproteinase-9 in plasma, bronchoalveolar lavage fluid, and lung tissues (P0.05 versus sham group), whereas curcumin pretreatment reduced these inflammatory markers. Curcumin had effective inhibitory effects on the expression of TLR4, MyD88, and NF-κB in lung tissues 24 h post-CPB (P0.05 versus vehicle group). Administration of curcumin remarkably decreased the lung injury score (L-Cur versus vehicle group, P = 0.024; H-Cur versus vehicle group, P = 0.013).Curcumin may be an alternative therapy for protecting CPB-induced lung injury by suppressing the expression of inflammatory cytokines. This anti-inflammatory effect of curcumin is partly related to the inhibition of TLR4, MyD88, and NF-κB.

Deep hypothermic circulatory arrest (DHCA) has been widely used in the operations involving the aortic arch and brain aneurysm since 1950s; but prolonged DHCA contributes significantly to neurological deficit which remains a major cause of postoperative morbidity and mortality. It has been reported that hydrogen exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical. In this study, DHCA treated rats developed a significant oxidative stress, inflammatory reaction and apoptosis. The administration of HRS resulted in a significant decrease in the brain injury, together with lower production of IL-1β, TNF-α, 8-OHdG and MDA as well as decreased activity of NOS while increased activity of SOD. The apoptotic index as well as the expressions of caspase-3 in brain tissue was significantly decreased after treatment. HRS administration significantly attenuated the severity of DHCA induced brain injury by mechanisms involving amelioration of oxidative stress, down-regulation of inflammatory factors and reduction of apoptosis.

Objective To establish a temporary pulmonary hilum clamping model for thoracic damage control surgery, as well as to determine the safety time latitude of this manipulation. Methods Pigs were anaesthetised and instrumented with a thermodilution cardiac output catheter. The left pulmonary hilum was clamped with a urethral catheter after thoracotomy, maintained for three different time periods (n = 6 for each group), 90 min (C90), 120 min (C120) and 150 min (C150) and then unclamped. Haemodynamic data were recorded and the serum samples were collected for D-dimer detection and other haematological analysis. A 1-cm3 pulmonary tissue of the left lower lobe was also obtained for histological study before clamping, at the end of clamping and at 0.5, 1, 1.5, 2 and 4 h after unclamping. Results Postoperative survival rate in each group of the pigs was as follows: 100% (all six) of C90, 83.3% (five of six) of C120, and 33.3% (two of six) of C150. Blood pressure (BP) and heart rate (HR) increased after clamping and gradually declined after unclamping. The animals of C150 group suffered highest BP and HR, respiratory index, pulmonary dynamic compliance and cardiac output. Platelet count showed no significant changes between the C90 and C120 groups, whereas a decline was noticed in the C150 group. Pulmonary vascular resistance increased significantly after pulmonary hilum clamping; when unclamped, there were minor changes in animals of C90 and C120 groups while there was a persistent elevation in the C150 group. An elevated D-dimer was detected in the C150 group, whereas it was normal in the C90 and C120 groups. There was significantly serious inflammatory cell infiltration, perivascular oedema and haemorrhagic infiltration in the C150 group compared with the C90 and C120 groups. Conclusions We established a pulmonary hilum clamping animal model for investigating pulmonary damage. By studying the haemodynamic and lung function changes of three different unilateral pulmonary hilum clamping time, it was determined that 120 min was the longest safety time for hilum clamping without lethal pulmonary injury in porcine models.

Objective: To explore the effects of thiazolidinediones (TZDs) pioglitazone on proliferation and differentiation of human preadipocytes. Methods: Omental adipose tissue biopsies were obtained from 15 patients who were undergoing elective open-abdominal surgery. The primary culture and differentiated induction of human preadipo-cytes were performed, and the human preadipo-cytes were treated with pioglitazone at different concentrations at proper moments. Dynamic morphological changes of the human preadipo-cytes were observed, and their proliferation and differentiation were assessed with Colorimetric MTT Assay and Oil Red 0 Staining. Results: After 24 hours and 72 hours with pioglitazone, 0.1umol/L (µmol/ml) pioglitazone increased the MTT values of the human preadipocytes by 25.3% and 34.8﹪, respectively (P＜0.05), while 1µmol/L pioglitazone by 27.4% and 26.6% (P＜0.05), compared with the control group without pioglitazone. The human preadipocytes with pioglitazone cumulated more adipose in the endochylema than those without pioglitazone obviously. 0.1µmol/L pioglitazone increased the differentiation degree of the human preadipocytes differentiated for 8-10 days by 44.81% arid 1umo1/L pioglitazone by 53.76% (P＜0.05). Conclusion: Thiazolidinediones pioglitazone may significantly promote the proliferation and differentiation of the human omental preadipocytes.

BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3 (BNIP3) has been explored in many human malignancies, but not in adenoid cystic carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of expression of BNIP3 in ACC tissues and cells and elucidated its correlations to hypoxia-induced autophagy. METHODS:Immunohistochemical and immunofluorescence staining were used toexplore BNIP3,HIF-1αand LC3 expression. RESULTS: BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P = 0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly correlated with TNM stage (P = 0.023) and histological grade (P = 0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P = 0.019). The expression of BNIP3 was correlated with HIF-1α expression (P = 0.011). The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P = 0.011). In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and could be a new target for gene therapy of adenoid cystic carcinoma.

Background Little is known about serum cystatin C as a marker of renal function in cardiac surgery patients. The aim of this study was to assess its utility post cardiopulmonary bypass (CPB). Methods 60 heart valve replacement patients were enrolled, and 26 of them had low-dose corticosteroid treatment on the first 3 days postoperatively. Serum creatinine, serum cystatin C and 24-h creatinine clearance rate (CCR) adjusted by body surface area were determined preoperation, days 1, 2, 3, 7 post operation. Results Serum creatinine increased and peaked at day 3 postoperatively, while cystatin C peaked at day 2, and the adjusted CCR also reached a minimum at day 2. The inverse of cystatin C correlated better with CCR than that of creatinine ( r = 0.751 vs. 0.629). Using adjusted CCR as “golden standard”, cystatin C was superior to creatinine in diagnosing renal dysfunction (area under the curve [AUC] for cystatin C 0.876, 95% confidence interval 81.8–93.4; AUC for creatinine 0.801, 95% confidence interval 72.5–87.7; p = 0.045). Low-dose corticosteroid treatment has no significant effect on cystatin C. Conclusion In agreement with many other investigators, the present findings support cystatin C is a reliable marker of renal function. It is superior to creatinine in patients post CPB.

Adenoid cystic carcinoma (ACC) is one of the most common types of salivary gland malignancy in the head and neck, and its aggressive ability to invade and metastasize is an important reason for its poor survival rates. Our previous investigations confirmed that autophagy‑associated gene expression is closely associated with the occurrence and development of ACC. On this basis, the present study further investigated hypoxia‑induced autophagy and its role in tumor invasion. Cobalt chloride (CoCl2) was used to mimic hypoxia. The results of the present study indicated that autophagosome formation and upregulation of autophagy‑associated microtubule‑associated protein 1 light chain 3 and Beclin 1 were observed in ACC‑M cells in response to CoCl2. The hypoxia‑inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K‑interacting protein 3 signaling pathway was involved in hypoxia‑induced autophagy in ACC. Furthermore, inhibition of autophagy by chloroquine markedly attenuated the tumor invasion induced by mimetic hypoxia in ACC. These results suggested that hypoxia‑induced autophagy may serve as a potential target for the future treatment of ACC.

Accumulating evidences have indicted the participation and repairing effects of endothelial progenitor cells (EPCs) on acute lung injury (ALI). Researchers have also revealed that erythropoietin (EPO) may exert multiple effects on EPCs including proliferative and adhesive properties. The present study was designed to investigate whether EPO can promote the healing efficiency of transplanted EPCs against ALI and the potential mechanism.Endothelial progenitor cells were derived from bone marrow mononuclear cells of BALB/c mice. In our in vitro studies, we tested the proproliferative and antiapoptotic effects of EPO on cultured EPCs. In our in vivo studies, we induced BALB/c mice ALI model by intratracheal instillation of lipopolysaccharide and treated with/without intravenous injection of enhanced green fluorescent protein-EPCs harvested from enhanced green fluorescent protein-BALB/c mice. Mice that received EPC transplantation either underwent EPO administration or not. The effects of EPO and EPC treatment on promoting pulmonary endothelial repair, decreasing pulmonary capillary permeability, alleviating pulmonary inflammation, improving gas exchange, and promoting pulmonary vessel angiogenesis were tested. The potential mechanisms that mediate EPO functions on EPC were also investigated.Our studies revealed a significant antiapoptotic property of EPO on cultured EPCs as well as its promotion on EPC proliferation. We also found the severity of ALI was reduced by EPC therapy, and the protective effects of EPCs were highly enhanced when combined with EPO administration. However, all these stimulating effects of EPO on EPCs were consisted with the expression of phospho-Akt and were abrogated by PI3K inhibitors.Transplanted EPCs directly incorporated into the injured pulmonary vessels and maintain the integrity of pulmonary endothelium. Erythropoietin improved the survival and proliferation of transplanted EPCs and recruited them to the injured sites to exert their repairing functions. PI3K/Akt pathway mediated EPO's functions on EPCs. The combination of EPO and EPC treatment may be a promising cell-based therapy for ALI patients.

Sepsis may result in lung injury through a complex cascade of events including interstitium infiltration of inflammatory cells. Quercetin, the most abundant dietary flavonoid found in various plants and food products, possesses potent anti-inflammatory and antioxidative properties. The purpose of this study was to investigate whether preventive administration of quercetin could exert beneficial effects on experimental septic acute lung injury induced by lipopolysaccharide (LPS). C57/BL6 mice were challenged with LPS and survival time was monitored from 0–96 h after LPS treatment. Quercetin markedly rescued lethality, improved survival time, and inhibited serum necrosis factor α, interleukin 1β, and interleukin 6, and nitric oxide (NO), and increased IL-10 secretion. Moreover, quercetin decreased lung pathological changes, myeloperoxidase activity, and malondialdehyde levels. Quercetin also reduced the lung permeability changes and neutrophil and macrophage recruitment to the bronchoalveolar lavage fluid compared to the vehicle. Additionally, quercetin significantly reduced COX-2, HMGB1, iNOS expression, and NF-κB p65 phosphorylation. These results suggest that treatment with quercetin in septic mice improved survival time and lung injury. Quercetin may be a promising potential therapeutic reagent for LPS-induced acute lung injury.

A novel iris image segmentation method using watershed and region merging is put forward. Total variation flow model is used to divide the eye image into structure part and texture part. Light spots in pupil are removed by closing. Watershed and region merging are both applied in structure part. Structure part is divided into separate parts. The regions may contain iris are labeled. Then, merging iris regions using average gray rule and total pixels rule. CASIA3.0-Interval iris image database is used to test the proposed method. Experiment results show that, the proposed method can segment iris images accurately and it can be used for different types of iris images.

Temsirolimus acts as a mammalian target of rapamycin (mTOR)-dependent autophagic inhibitor. In order to clarify its effects and mechanisms on human salivary adenoid cystic carcinoma (ACC), we examined whether temsirolimus induced autophagy as the mTOR inhibitor in ACC, both in vitro and in vivo. In this study, MTT assay showed that the inhibition effect of temsirolimus assumed an obvious dose-response relationship on ACC-M cells, and the 50% inhibitory concentration (IC(50)) approached 20 μmol/l; numerous autophagosomes were observed by the transmission electron microscopy (TEM) in temsirolimus treatment groups; notably, expression of LC3 and Beclin1 was significantly up-regulated by temsirolimus. More importantly, the xenograft model provided further evidence of temsirolimus-induced autophagy in vivo by inhibiting mTOR activation as well as up-regulation the expression of Beclin1. These results suggest that temsirolimus could act as an mTOR inhibitor to induce autophagy in adenoid cystic carcinoma both in vitro and in vivo.

Ischemia-reperfusion (I/R) injury may influence graft function following transplantation. Ulinastatin, a urinary trypsin inhibitor has been shown to attenuate I/R injury in various organs such as intestine, heart, and kidney in animals. The present experiment was designed to evaluate the effect of pretreatment with ulinastatin on I/R-induced lung injury.After establishing a constant left lung warm ischemia-reperfusion model in rats, 45 animals were randomly divided into three experimental groups: sham group (n = 15), IR group (n = 15), and ulinastatin (5000 U/kg pre-ischemia) + IR group (n = 15). The lung injury was evaluated by tissue myeloperoxidase activity, with simultaneous estimation of the serum concentration of TNFalpha.The ulinastatin-pretreated animals exhibited markedly decreased lung tissue myeloperoxidase activity (P.05). Blood gas analysis demonstrated, that the treated animals had significantly ameliorated pulmonary oxygenation (P.05). The serum concentration of TNF-alpha in the ulinastatin-pretreated group was markedly decreased compared with that of the I/R group (P.05).Ulinastatin attenuated I/R-induced lung injury. This function is partly related to the capacity of the agent to inhibit myeloperoxidase activity in lung tissue and decrease systemic expression to TNF-alpha.

Background Endothelial progenitor cells (EPCs) are involved in endothelium repair of acute lung injury (ALI). Numerous studies have demonstrated that statins can promote EPC function in vitro and in vivo; therefore, the purpose of this study was to determine whether simvastatin enhances the function of EPCs participating in the repair of ALI. Methods BALB/C mice were initially pretreated with simvastatin by intraperitoneal administration 24 h before, and again at the time of, intratracheal instillation of lipopolysaccharide (LPS) and subsequently treated with EPCs by IV transplantation 2 h later. The effects of capillary permeability, endothelium repair, and inflammatory cytokines were measured. Results This study revealed that both simvastatin administration and EPC transplantation can reduce the severity of LPS-induced ALI in mice, and the effect can be further improved by combining the two therapies. Conclusions The administration of simvastatin and EPC transplantation can reduce the severity of LPS-induced ALI in mice, and improvement is moderately enhanced in some respects when EPC transplantation is combined with simvastatin administration. The beneficial role of simvastatin on EPCs may be a component of its pleiotropic effects. Although the exact mechanism remains unknown, the combined administration of simvastatin and EPC transplantation may be a potentially important, cell-based, inflammation-mediated therapy for patients with ALI/ARDS.

Objective: Acute lung injury is a common complication after cardiopulmonary bypass (CPB). Oxidative damage greatly impacts CPB-induced lung ischemic pathogenesis and may represent a target for treatment. We aimed to investigate whether curcumin upregulates heme oxygenase 1 (HO-1) expression and ameliorates lung injury in a rat CPB model. Methods: A total of 80 male Sprague-Dawley rats were divided into 2 sets of 5 groups (n = 8 per group): sham; control (CPB); vehicle; low-dose curcumin (L-Cur); and high-dose curcumin (H-Cur). Animals were pretreated with a single intraperitoneal injection of vehicle, L-Cur (50 mg/kg), or H-Cur (200 mg/kg) 2 hours prior to CPB. Lung tissue, serum, and bronchoalveolar lavage fluid was harvested 2 or 24 hours postoperatively. In the control group, CPB-induced lung injury was confirmed by histopathologic examination and a significantly increased wet-to-dry lung weight ratio and pulmonary permeability index value was observed ( P < .05 vs sham group). Cardiopulmonary bypass was associated with a marked rise in the level of malondialdehyde and myeloperoxidase and a fall in superoxide dismutase 2 and 24 hours after surgery ( P < .05 vs sham group). Administration of curcumin ameliorated lung damage and reversed the oxidative stress markers in a partially dose-dependent manner ( P < .05 vs vehicle group). Furthermore, HO-1 gene transcription and protein expression were elevated to a greater extent in the lungs after curcumin pretreatment compared with the vehicle pretreatment. Conclusions: Curcumin has the potential to provide protection from CPB-induced lung damage reflected in the expression of oxidative stress markers. The antioxidant effect of curcumin may be partly related to upregulation of HO-1.

Inflammation has been implicated as a contributing factor in the development of abdominal aortic aneurysms (AAA). Quercetin, a natural flavonoid with anti-inflammatory properties, is known for its beneficial effects on vascular disease. In this study, we examined the effects of quercetin to inflammatory cell infiltration, subsequent expression of cytokines and activation of proteases on the expansion of experimental AAA. Aneurysms were induced by abluminal application of calcium chloride in C57/BL6 mice. Quercetin (60 mg/kg) was administered once daily by gavage beginning 2 weeks before AAA induction and continuing for 8 weeks. Mice treated with quercetin exhibited a 32.7% reduction in aortic size compared with vehicle-treated controls. Prevention of AAA was associated with preservation of medial structure, as well as a relative reduction in macrophage and CD3(+) T cell infiltration in aortic tissue, inflammatory cytokines release and nuclear factor κB activation. Quercetin also reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, cathepsin B, and cathepsin K in aortic tissue. In addition, quercetin treatment increased tissue inhibitors of metalloproteinases (TIMP)-1 gene expression. These data indicate that quercetin may be useful for the prevention and treatment of AAA via blocking the inflammatory response and inhibiting the proteases involved in the pathogenesis of this disease.

Acute renal injury is one of the most frequent complications after cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of erythropoietin (EPO) on CPB-induced renal injury in a rat model. Male Sprague-Dawley rats were randomly divided into three groups, sham-operated group (sham), control CPB group (control), erythropoietin CPB group (EPO). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2 and 24 h post-operation, and the kidneys were harvested 24 h postoperatively and observed by optical microscopy. Levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were assayed. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6(IL-6) levels in the renal tissues were evaluated by the method of enzyme linked immunosorbent assay (ELISA). Protein and mRNA levels of nuclear factor kappa B p65 (NF-κB p65), intercellular adhesion molecule-1 (ICAM-1) were also determined using western blot and real-time PCR respectively. Serum Cr and BUN levels as well as TNF-α, IL-1β and IL-6 levels in renal tissues in control group were significantly higher than those in the sham group. However, the levels of above biomarkers were markedly decreased in EPO group when comparing with control group. Furthermore, NF-κB p65, ICAM-1 protein and mRNA expression were significantly down-regulated in EPO group comparing with control group. In addition, microscopic examinations revealed that histological injury was alleviated when treated with EPO. The results indicated that EPO potently protected against CPB-induced acute renal injury and inhibited expression of NF-κB p65 and inflammatory response.

In this paper, a new stochastic model based on cellular automata is established to simulate the occurrence and development of Schistosoma japonicum (S. japonicum) infection in an endemic population. We included the process of the pathogen invasion from exposure to worm development and till worm death when the infection is cleared in the model. We further utilized the model to predict the prevalence as the outcomes of the selected chemotherapy carried out in Jiahu village. Comparing model predicted prevalence and intensities with the observed parameters, it is anticipated that our cellular automaton transmission model can serve as a tool for studying schistosomiasis transmission dynamics in endemic areas.

Background Temporarily pulmonary hilum clamping is available for the trauma surgeon to deal with serious pulmonary injuries, but the physiologic influence needs further evaluation. This study was to establish a temporary pulmonary hilum clamping model for thoracic damage-control surgery and determine the safety time latitude of this manipulation. Methods After anesthetized and catheter instrumented, the left pulmonary hilus of pigs were clamped with a urethral catheter after thoracotomy maintained for three different time period, 90 minutes (C90), 120 minutes (C120), and 150 minutes (C150), and then unclamped. Hemodynamic data were recorded and serum samples were collected for d-dimer detection and other hematology analysis, as well as 1 cm3 pulmonary tissue was obtained for histologic study before clamping, at the end of clamping, and at 0.5, 1, 1.5, 2, and 4 hours after unclamping. Results There were 100% of C90, 83.3% of C120, and 33.3% of C150 pigs survived. Animals of C150 group suffered highest blood pressure and heart rate, respiratory index, pulmonary dynamic compliance, and cardiac output. Pulmonary vascular resistance, platelet count, and D-dimer showed minor significant changes between C90 and C120 groups, whereas a marked changes in C150 animals during the study. There were much more serious histologic changes in C150 group compared with C90 and C120 groups. Conclusions We established a pulmonary hilum clamping animal model for pulmonary damage investigation. It was determined that 120 minutes was the longest safety time for hilum clamping without lethal pulmonary injury in porcine.

Statins have been shown to downregulate the systemic inflammatory response after cardiopulmonary bypass. However, the role of statins as anti-inflammatory agents in heart tissue remains unknown. The aim of this study was to test whether statin pretreatment attenuates local inflammatory cytokines production in heart and to explore whether the underlying mechanism involves peroxisome proliferator-activated receptor (PPAR) γ. A rat model of cardiopulmonary bypass was established. The animals were pretreated with simvastatin 5 mg/kg/day or 10 mg/kg/day for 7 days before operation. The serum concentration and myocardial level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 was evaluated by enzyme linked immunosorbent assay. The polymorphonuclear neutrophils accumulation in heart tissue was determined by myeloperoxidase activity assay. The activity of nuclear factor (NF)-κB and PPARγ in the heart was determined by electrophoretic mobility shift assay. The myocardial PPARγ expression was also examined by immunohistochemistry. The systemic and local TNF-α, IL-6 and MCP-1 were all significantly elevated after cardiopulmonary bypass. In contrast, simvastatin pretreatment significantly decreases the serum and myocardial expression level of above cytokines, myocardial myeloperoxidase activity and myocardial NF-κB activity. However, there was an evident increase in the activity and expression of PPARγ. In conclusion, simvastatin pretreatment not only attenuates acute systemic and local inflammatory response induced by cardiopulmonary bypass. The anti-inflammatory effect of simvastatin in myocardium may be partly related to the activation of PPARγ and inhibition of NF-κB.

AIM: To investigate microvascular injury quantitatively in the small bowel with respect to cardiopulmonary bypass (CPB) and related mechanisms. METHODS: In 10 male SD rats, normothermic CPB was established and continued with a flow rate of 100-150 mL/kg per minute for 60 min, while another 10 sham-operated animals served as controls. An approximate 10-cm loop of the terminal ileum was exteriorized for observation by means of intravital fluorescence microscopy. The small bowel microcirculatory network including arterioles, capillaries, and collecting venules was observed prior to CPB, CPB 30 min, CPB 60 min, post-CPB 60 min and post-CPB 120 min. The intestinal capillary perfusion, microvascular permeability and leukocyte adherence were also measured. RESULTS: The systemic hemodynamics remained stable throughout the experiment in both groups. In CPB animals, significant arteriolar vasoconstriction, blood velocity reduction and functional capillary density diminution were found. As concomitances, exaggerated albumin extravasation and increased leukocyte accumulation were also noted. These changes were more pronounced and there were no signs of restitution at the end of the observation period. CONCLUSION: CPB induces significant microcirculatory injury of the small bowel in rats. The major underlying mechanisms are blood flow redistribution and generalized inflammatory response associated with CPB.

Erythropoietin (Epo) was recently defined as an endogenous agent with more than hematopoietic functions. Previously we explored the potential of this agent to ameliorate lung ischemia-reperfusion (I/R) injury. The present study aims to determine the optimal dose and timing of administration for improving lung injury, and to further investigate the mechanisms by which Epo ameliorates lung I/R injury. The left lungs of Sprague-Dawley rats underwent 90 min ischemia and 120 min reperfusion. Firstly, animals in different groups were intraperitoneally injected with various doses of recombined human erythropoietin (rhEpo) 24 h prior to operation, 2 h prior to operation, or after the onset of reperfusion. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were evaluated. Treatment with 3 KU/kg rhEpo 2 h prior to operation was optimal for attenuating pulmonary MPO activity and MDA content. With such treatment, ultrastructural changes of pneumocytes were observed, and the pneumocyte apoptosis index was also determined by terminal dUTP nick-end labeling method. The plasma concentrations of tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP)-9 were evaluated by enzyme-linked immunosorbent assay, and pulmonary expression by immunohistochemistry. When pretreated with rhEpo, the pneumocyte ultrastructure was predominantly maintained and the pulmonary apoptosis index was markedly reduced. In comparison with untreated animals, in treated animals the plasma concentrations of TNF-alpha and MMP-9 were significantly decreased, and their expression in lung tissue was markedly reduced as well. The results indicated that Epo potently protected against lung I/R injury by inhibiting systemic and local expression of TNF-alpha and MMP-9.