Silencing FHL2 inhibits bleomycin-induced pulmonary fibrosis through the TGF-ß1/Smad signaling pathway.

OBJECTIVE: This study aimed to investigate the inhibiting effects of FHL2 and Arbutin on cell fibrosis and their possible mechanisms. METHODS: The mRNA expression of FHL2 in pulmonary fibrosis tissues was analyzed by bioinformatics. TGF⁃ß1 induced fibrosis of mouse lung fibroblast (Mlg) and mouse primary pulmonary fibroblast (PPF) in rat's lung fibroblasts. FHL2 siRNA was transfected into Mlg and mouse PPF cells to inhibit FHL2. FHL2, α-smooth muscle actin (α-SMA), collagen 1 (Col I), and Fibronectin (Fn) were detected by qRT-PCR. Western blot expression levels of Smad3, p-Smad3, Smad2, and p-Smad2 proteins in cells. High-throughput drug screening for FHL2 inhibitors and the inhibitory effect of Arbutin on pulmonary fibrosis were validated in cellular and animal models of pulmonary fibrosis. RESULTS: The mRNA expression of FHL2 in lung fiber tissue was increased. Meanwhile, the decrease of FHL2 expression significantly inhibited the cellular fibrosis morphological changes of rat's lung fibroblasts (Mlgs) and primary lung fibroblasts (PPFs). The expression levels of α⁃SMA, Col I, and Fn were decreased. High-throughput screening showed that Arbutin targeted FHL2. Arbutin alleviated bleomycin (BLM)-induced pulmonary fibrosis in rats by inhibiting FHL2 and then the TGF-ß1/Smad signaling pathway. CONCLUSION: Inhibition of FHL2 can effectively reduce the fibrosis process induced by TGF⁃ß1 and bleomycin, and then inhibit the fibrosis.

Short- (30-90 days) and mid-term (1-3 years) outcomes and prognostic factors of patients with esophageal cancer undergoing surgical treatments.

BACKGROUND: The factors influencing the prognosis of patients with esophageal cancer vary among studies and are still poorly known. AIM: To determine the factors associated with survival in patients with esophageal cancer. METHODS: This retrospective study included patients with esophageal cancer admitted between January 2017 and March 2020 at Heping Hospital Affiliated to Changzhi Medical College. All patients were treated according to the available guidelines. Follow-up was censored in October 2020. Univariable and multivariable Cox regression analyses were used to determine the independent risk factors for overall survival (OS). RESULTS: In total, 307 patients were included. Their median age was 64 (range, 44-79) years, 63.5% were male, and the median disease course was 2 (0.1-36) months. The median tumor size was 3 (0-10) cm. Most patients were T3 (29.6%), N0 (70.0%). Most tumors were grade 2 (48.2%), and 87.3% were squamous cell carcinoma. The in-hospital mortality was 16.9%, the 30-day mortality was 19.9%, and the 90-day mortality was 25.4%. The cumulative OS rates at the last follow-up were 82.1% (95%CI: 67.7%-96.5%) for stage 0/I/II and 47.4% (95%CI: 16.5-78.6%) for stage III/IVA (P < 0.001). The multivariable analysis showed that creatinine levels (HR = 1.02, 95%CI: 1.00-1.03, P = 0.050), pTNM III/IVA (HR = 4.19, 95%CI: 2.19-8.01, P < 0.001), adjuvant radiotherapy and/or chemotherapy (HR = 0.23, 95%CI: 0.11-0.49), and the Comprehensive Complication Index (CCI) (HR = 1.02, 95%CI: 1.004-1.03, P = 0.011) were independently associated with OS. CONCLUSION: The survival of patients with esophageal cancer is poor, especially those with pTNM III/IVA. pTNM stage III/IVA, CCI, and adjuvant therapy (radiotherapy and/or chemotherapy) are independently associated with OS.

Impact of unintentional coronary angiography on outcomes of emergency surgery in acute type A aortic dissection: a retrospective study.

BACKGROUND: This study investigated the impact of coronary angiography on outcomes of emergency operation in acute type A aortic dissection (ATAAD) patients who were initially misdiagnosed as an acute coronary syndrome. METHODS: From October 2016 to April 2019, 129 patients underwent emergency operation for ATAAD in our institution, including 21 patients (16.3%, coronary angiography group) who received preoperative coronary angiography without knowledge of the ATAAD, and the rest 108 did not (Non-coronary angiography group). Preoperative clinical characteristics, 30-day mortality and postoperative complications were compared. Multivariable logistic regression was performed to confirm the independent prognostic factors for short-term and long-term outcomes. RESULTS: Patients undergoing coronary angiography had higher prevalence of preoperative hypotension or shock (61.9% vs 35.2%, P = 0.022), ischemic changes on electrocardiogram (66.7% vs 37.0%, P = 0.012), platelet inhibition (ADP-induced inhibition 92.0% vs 46.0%, P = 0.001), and coronary involvement (66.7% vs 30.6%, P = 0.002). 30-day mortality was 4.8% versus 9.3% (P = 0.84). Coronary angiography group had more intraoperative bleeding (1900 ml vs 1500 ml, P = 0.013) and chest-tube drainage on the first postoperative day (1040 ml vs 595 ml, P = 0.028). However, preoperative coronary angiography was not independent risk factors for 30-day mortality (OR 0.171, 95%CI 0.013-2.174, P = 0.173) and overall survival (HR 0.407; 95%CI 0.080-2.057; P = 0.277). CONCLUSION: Patients undergoing coronary angiography carried a higher risk of preoperative hemodynamic instability, myocardial ischemia, and perioperative bleeding. However, unintentional coronary angiography did not have a significant impact on short-term and long-term outcomes of emergency surgery in ATAAD.

mmu-microRNA-92a-3p attenuates pulmonary fibrosis by modulating Cpeb4-mediated Smad2/3 signaling pathway.

Pulmonary fibrosis (PF) is a chronic lung disorder, in which the mechanism of mmu-microRNA (miR)-92a-3p is not elucidated clearly. The present work was proposed to disclose mmu-miR-92a-3p-focused mechanism in PF with cytoplasmic polyadenylation element-binding protein 4 (Cpeb4)/Smad2/3 axis. PF was induced in mice by the intratracheal injection of bleomycin (BLM). Then, the BLM-treated mice were injected with mmu-miR-92a-3p- and/or Cpeb4-related adenovirus vectors. mmu-miR-92a-3p, Cpeb4, and Smad2/3 expression in lung tissues were examined. Alveolar cell apoptosis and collagen deposition in lung tissues and inflammatory factors in serum were observed. The interaction between mmu-miR-92a-3p and Cpeb4 was explored. Lowly expressed mmu-miR-92a-3p and highly expressed Cpeb4 and Smad2/3 were manifested in BLM-induced PF mice. BLM-induced PF mice exhibited enhanced inflammation, alveolar cell apoptosis, and collagen deposition, which would be attenuated by upregulating mmu-miR-92a-3p or downregulating Cpeb4. mmu-miR-92a-3p targeted Cpeb4. Upregulating mmu-miR-92a-3p or downregulating Cpeb4 inactivated the Smad2/3 signaling pathway in BLM-induced PF mice. It is elaborated that mmu-miR-92a-3p attenuates the process of PF by modulating Cpeb4-mediated Smad2/3 signaling pathway, renewing the molecular mechanism of PF.

Identification of KIF4A as a prognostic biomarker for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common and aggressive tumor worldwide, and the long-term survival of these patients remains poor. Three databases (GSE17351, GSE20347, and GSE100942) were obtained from Gene Expression Omnibus, and 193 differentially expressed genes including 56 upregulated and 137 downregulated genes were identified by paired test using limma R package. Then, functional enrichments by gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed these genes were mainly related protein digestion and absorption, and IL-17 signaling pathway. We then constructed a protein-protein interaction network and cytoHubba module to determine the six hub genes and overall survival analysis of the six hub genes were evaluated by UALCAN and GEPIA2 analysis. Ultimately, the experimental results confirmed the KIF4A was overexpressed in the ESCC tissues and cell lines compared with the normal esophageal mucosal tissues and was linked to poor prognosis. Moreover, we also revealed that KIF4A facilitates proliferation, cell cycle, migration, and invasion of ESCC in vivo and in vitro. Overall, these findings demonstrated that KIF4A could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in ESCC patients.

NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway.

Hypertension is characterized by endothelial dysfunction, vascular remodeling, and rearrangement of the extracellular matrix. Besides, the pathogenesis of hypertension is closely related to excess generation of reactive oxygen species (ROS). Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis that influences the activity of NAD-dependent enzymes, such as sirtuins, which possess NAD-dependent protein deacetylase activity and cleave NAD during the deacetylation cycle. Recently, NAMPT has been shown to play a crucial role in various diseases associated with oxidative stress. However, the function and regulation of NAMPT in hypertension have not been extensively explored. In the present study, we identified NAMPT as a crucial regulator of hypertension, because NAMPT expression was significantly downregulated in both patients with hypertension and experimental animals. NAMPT knockout (NAMPT+/-) mice exhibited a significantly higher blood pressure and ROS levels after stimulation with angiotensin II (Ang II) than wild-type mice, and the administration of recombinant human NAMPT (rhNAMPT) reversed this effect. In vivo, overexpression of NAMPT protected against angiotensin II- (Ang II-) induced hypertension by inhibiting ROS production via sirtuin 1 in mouse aortic endothelial cells (MAECs) and mouse aortic vascular smooth muscle cells (MOVAs). In turn, NAMPT alleviated the ROS-induced mitogen-activated protein kinase (MAPK) pathway. In conclusion, NAMPT might be a novel biomarker and a therapeutic target in hypertension.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells.

Endothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

Identification of genome variations in patients with lung adenocarcinoma using whole genome re­sequencing.

Lung adenocarcinoma is one of the types of non­small cell lung carcinoma, which tends to be treated with surgical therapy rather than radiation therapy. It occurs in smokers and non­smokers, and is the most common form of lung cancer among non­smokers and women. Gene rearrangements, including ALK, ROS1 and RET, and gene mutations, including epidermal growth factor receptor (EGFR), HER2, Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide­3­kinase, catalytic, α polypeptide and MET, have been identified in lung adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example erlotinib, gefitinib and afatinib, which are EGFR inhibitors. The aim of the present study was to further investigate genome variations in lung adenocarcinoma. Single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), structural variations (SVs) and copy number variations (CNVs) were identified in the whole genome from four patients with adenocarcinoma using a whole genome re­sequencing method performed on the Illumina HiSeq Xten platform. In total, ~415 GB of clean reads were obtained, the average sequencing depth was 31.10­fold, and 99.29% of the reference genome was covered by the clean reads. An average of 3,364,270 SNPs was identified, 98.76% of which were matched to the SNP database (dbSNP), and an average of 453,547 InDels were identified, 28.28% of which were in the dbSNP. The present study also identified a total of 13,050 SVs and 886 CNVs. The majority of the SVs were deletions (74.25%) and the major CNVs were in intergenic regions and coding sequence regions. In conclusion, the results of the present study generated an output of the genome alterations in lung adenocarcinoma, and provided a foundation for further investigation of the pathogenesis of lung adenocarcinoma.

Cardiac Cavernous Hemangioma Coexisting With Pulmonary Cavernous Hemangiomas and Giant Hepatic Hemangioma.

We describe a case of cardiac cavernous hemangioma with coexisting pulmonary cavernous hemangiomas and hepatic hemangioma. A 35-year-old woman who had previously received a living donor liver transplant to cure giant hepatic hemangioma was seen because of chest pain. A cardiac neoplasm and multiple pulmonary nodules were detected. The tumor was surgically removed, and biopsy specimens were taken from the lung nodules. Histopathologic examination confirmed that both lesions were cavernous hemangiomas. The patient was discharged without adverse events postoperatively. Cardiac hemangioma is an extremely rare entity; the present case is unique for its multiorgan involvement. Suspicion of this entity should be aroused if the imaging manifestation suggests a vascular nature.

Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells.

CD22 is a surface immunoglobulin implicated in negative regulation of B cell receptor (BCR) signaling; particularly inhibiting intracellular Ca2+ (Ca2+i)signals. Its cytoplasmic tail contains six tyrosine residues (Y773/Y783/Y817/Y828/Y843/Y863, designated Y1~Y6 respectively), including three (Y2/5/6) lying within immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that serve to recruit the protein tyrosine phosphatase SHP-1 after BCR activation-induced phosphorylation. The mechanism of inhibiting Ca2+i by CD22 has been poorly understood. Previous study demonstrated that CD22 associated with plasma membrane calcium-ATPase (PMCA) and enhanced its activity (Chen, J. et al. Nat Immunol 2004;5:651-7). The association is dependent on BCR activation-induced cytoplasmic tyrosine phosphorylation, because CD22 with either all six tyrosines mutated to phenylalanines or cytoplasmic tail truncated loses its ability to associate with PMCA. However, which individual or a group of tyrosine residues determine the association and how CD22 and PMCA interacts, are still unclear. In this study, by using a series of CD22 tyrosine mutants, we found that ITIM Y2/5/6 accounts for 34.3~37.1% Ca2+i inhibition but is irrelevant for CD22/PMCA association. Non-ITIM Y4 and its YEND motif contribute to the remaining 69.4~71.7% Ca2+i inhibition and is the binding site for PMCA-associated Grb2. Grb2, independently of BCR cross-linking, is constitutively associated with and directly binds to PMCA in both chicken and human B cells. Knockout of Grb2 by CRISPR/Cas9 completely disrupted the CD22/PMCA association. Thus, our results demonstrate for the first time that in addition to previously-identified ITIM/SHP-1-dependent pathway, CD22 holds a major pathway of negative regulation of Ca2+i signal, which is ITIM/SHP-1-independent, but Y4/Grb2/PMCA-dependent.

Literature Analysis of the Treatment of Benign Esophageal Disease with Stent.

To analyze the efficacy and safety of benign esophageal disease used biodegradable (BD) stent or metal stent. The English literatures of benign esophageal disease that were treated by biodegradable or metal stents implantation were retrieved and summarized. In all 323 benign esophageal disease, the most common etiologies were benign refractory stricture, surgical anastomotic stricture and esophageal fistula/leak/perforation, but the main characteristics between the two groups were not significantly different. One hundred fifty-four cases were completely healed by using BD stents or self-expandable metal stents (SEMS) (47.7 %). Clinical success was achieved in 47.7 % of all patients and there was no significant difference between BD stents (51 %) and SEMS (46.2 %) (P = 0.472), while stent migration occurred more frequently with SEMS (33.9 %) than with BD stent (19.6 %) (P ≤ 0.05), and tissue in- or overgrowth occurred more frequently with SEMS (22.2 %) than with BD stents (8.8 %) (P ≤ 0.05). Furthermore, the time about degradation of BD stents in esophageal was longer than removal of SEMS from the esophagus (P ≤ 0.05). Placement of BD stents or SEMS provides effective and safe relief for benign esophageal disease. Clinical success and mortality were not significantly different. BD stents offers an advantage of fewer complications. Although stent placement is a viable strategy in patients with benign esophageal disease, the ideal treatment strategy and further randomized trials with large number of patients are needed.

Circulating cytokine portraits can differentiate between allograft rejection and pulmonary infection in cardiac transplant rats.

OBJECTIVES: Cardiac rejection and infection are the leading causes of morbidity and mortality after transplant representing with similar non-specific symptoms. Early discrimination is crucial yet challenging. We proposed that aberrant serum cytokine portraits exist in pulmonary infection and allograft rejection, and such profiles might aid in timely differential diagnosis. METHODS: Lewis rat received Wistar rat heart allografts. Allograft rejection (n = 5) and pulmonary infection (n = 7) were induced via cessation of cyclosporine injection and intratracheal inoculation of Pseudomonas aeruginosa, respectively, and pathologically confirmed. A non-rejection and non-infection group (n = 5) was served as healthy controls. The circulating cytokine profiles of the study objects were then simultaneously measured using a multiplex quantitative cytokine array. RESULTS: Thirteen cytokines [B7-2, ß-nerve growth factor (NGF), chemokine (C-X3-C motif) ligand 1 (Fractalkine), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interleukin beta (IL-ß), IL-2, IL-4, IL-10, chemokine (C-X-C motif) ligand 5 (LIX), L-selectin, chemokine (C-C motif) ligand 2 (MCP-1), brain creatine kinase (TCK-1) and tumour necrosis factor alpha (TNF-α)] were up-regulated in allograft rejecting animals. Among them, B7-2, ß-NGF, Fractalkine, GM-CSF, IFN-γ, IL-ß, IL-2, IL-4, LIX, MCP-1 and TCK-1 were significantly increased compared with infection rats (all P-values <0.05). B7-2, CNIC-1 and CNIC-2 were increased in infection animals when compared with healthy controls (900.85 ± 259.30 vs 175.04 ± 161.07 pg/ml, 319.68 ± 264.91 vs 13.50 ± 0.00 pg/ml and 51.424 ± 29.51 vs 5.24 ± 1.30 pg/ml, respectively, all P-values <0.05). CONCLUSIONS: The present study demonstrated fluctuations in circulating cytokine portraits in cardiac allograft rejection and bacterial pulmonary infection after transplant. Such disease-specific cytokine patterns might facilitate early discrimination between rejection and infection.

Impact of mild preoperative renal insufficiency on in-hospital and long-term outcomes after off-pump coronary artery bypass grafting: a retrospective propensity score matching analysis.

BACKGROUND: Mild preoperative renal insufficiency is not rare in patients receiving isolated off-pump coronary artery bypass grafting surgery (OPCAB) surgery. However, there is less study aimed to evaluate the impact of mild preoperative renal insufficiency on in-hospital and follow-up outcomes after isolated OPCAB surgery. This single-centre, retrospective propensity score matching study aimed to evaluate the impact of mild preoperative renal insufficiency on in-hospital and long-term outcomes after first isolated OPCAB surgery. METHODS: After propensity score matching, 1236 patients with preoperative estimated glomerular filtration rate (eGFR) of more than 60 ml/min/1.73 m(2) undergoing first isolated OPCAB surgery from January 2007 to December 2011 were entered into this study and were divided to normal group (eGFR ≥ 90 ml/min/1.73 m(2), n = 618) and mild group (eGFR of 60-89 ml/min/1.73 m(2), n = 618). The in-hospital and long-term outcomes were investigated and retrospectively analyzed. RESULTS: The 2 propensity score-matched groups had similar baseline and procedural characteristics except the baseline eGFR. Thirty-five patients died during the same hospitalization or within 30 days of operation, with a surgical mortality of 2.8 %. Sixty-seven patients died during follow-up, with a long-term survival of 94.1 %. Univariate factor analysis showed that the 2 propensity score-matched groups have similar rates among in-hospital outcomes. Kaplan-Meier curves displayed a similar in-hospital survival between the 2 groups (χ(2) = 0.728, p = 0.393), while a better long-term survival in patients with normal preoperative renal function compared with mild preoperative renal insufficiency (χ(2) = 4.722, p = 0.030). After Cox proportional model was used, the hazard ratio for long-term mortality in patients with mild preoperative renal insufficiency compared with normal preoperative renal function was 1.72 (95 % CI 1.06-2.83, p = 0.032). CONCLUSIONS: Mild preoperative renal insufficiency compared with normal preoperative renal function reduced long-term survival, without evidence of worse in-hospital outcomes.

Oncological and surgical outcomes of minimally invasive versus open esophagectomy for esophageal squamous cell carcinoma: a matched-pair comparative study.

Only a few series have demonstrated the safety and efficacy of minimally invasive esophagectomy (MIE) for esophageal squamous cell carcinoma and the benefits of this approach. This report describes the results of a pair-matched comparative study between minimally invasive and open esophagectomy (OE) for esophageal squamous cell carcinoma. Patients were retrospectively matched in pairs for the following criteria: age, sex, American Society of Anesthesiology (ASA) score, clinical TNM stage, tumor location, and type of resection. A total of 97 patients undergoing MIE were compared with patients undergoing OE during the same period. Operative, postoperative, and oncologic outcomes were compared. Significantly less bleeding was observed in the MIE group (P = 0.001). Transfusion was required for three patients in the MIE group and ten patients in the OE group (P = 0.044). Overall morbidity was similar in the two groups. The hospital stay was significantly shorter for the patients undergoing MIE (P = 0.027). The surgical margin and tumor stage were not affected by MIE. The overall survival rates in the MIE group were 54% at 5 years and 46% in the OE group (P = 0.631). The disease-free survival rates in the MIE group were 45% at 5 years, 41% in the OE group (P = 0.704). In summary, MIE for esophageal squamous cell carcinoma for selected patients gave a better postoperative outcome without oncologic consequences.

Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.

OBJECTIVES: The excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia. METHODS: In a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry. RESULTS: Transfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA. CONCLUSIONS: We confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model.

Impact of smoking on early clinical outcomes in patients undergoing coronary artery bypass grafting surgery.

BACKGROUND: To evaluate the impact of persistent smoking versus smoking cessation over one month prior to surgery on early clinical outcomes in Chinese patients undergoing isolated coronary artery bypass grafting (CABG) surgery in a retrospective study. METHODS: The peri-operative data of consecutive well-documented patients undergoing isolated CABG surgery from January 2007 to December 2013 were investigated and retrospectively analyzed. All included patients were divided into either a non-smoking group or a smoking group according to preoperative smoking records. Furthermore, smokers were divided into either a former smoking subgroup (smokers with smoking cessation over 1 month before surgery) or a current smoking subgroup (persistent smokers). RESULTS: A total of 3730 consecutive patients (3207 male patients and mean 63.6 ± 9.5 years) undergoing isolated CABG surgery were analyzed. Persistent smokers had significantly higher incidence of postoperative pulmonary complications as compared to non-smokers (7.8% vs. 4.5%, p = 0.0002). No significantly differences in both surgical mortality and major postoperative morbidities between smokers with smoking cessation over 1 month before surgery and non-smokers were found. In multiple logistic regression analysis, the risk of postoperative pulmonary complications in persistent smokers was 2.41 times than that in non-smokers, whereas the risk of postoperative pulmonary complications in smokers with smoking cessation over 1 month before surgery was similar to non-smokers. CONCLUSIONS: Persistent smokers had a higher incidence of pulmonary complications following CABG as compared to non-smokers. Smoking cessation more than 1 month before surgery was expected to reduce early major morbidities following CABG surgery.

Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers.

It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein-protein or gene-gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed.

A rat model of pulmonary infection after cardiac transplant.

OBJECTIVES: Cardiac allograft rejection and infection are leading causes of morbidity and mortality after transplant. The lack of an animal model has hindered related research. We have developed a rat model of pulmonary infection after cardiac transplant to address this issue. MATERIALS AND METHODS: Lewis rats received Wistar rat heart allografts, cardiac rejection was induced by cessation of cyclosporine injection, and pulmonary infection was induced by Pseudomonas aeruginosa intrabronchial inoculation. Development of pulmonary infection and/or heart rejection was assessed by histopathology. RESULTS: Histopathologic findings showed that a dose of 2 × 108 colony forming units of Pseudomonas aeruginosa intrabronchial inoculation is sufficient to cause severe pneumonia without being lethal to transplanted animals. Daily administration of 10 mg/kg of cyclosporine reliably suppressed rejection, and withdrawal for 7 days can obtain a consistent International Society for Heart and Lung Transplantation 3R rejection. CONCLUSIONS: The current study represents a simple and effective rat model of pulmonary infection along, or in combination, with rejection after heart transplant, which can be used for research of infection-rejection in cardiac transplant settings.