Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

[Effects of maize and peanut co-ridge intercropping on crop photosynthetic characteristics and intercropping advantages]. / çŽ‰ç±³å’ŒèŠ±ç”ŸåŒåž„é—´ä½œå¯¹ä½œç‰©å ‰åˆç‰¹æ€§å’Œé—´ä½œä¼˜åŠ¿çš„å½±å“.

To clarify the photosynthetic mechanism contributing to the enhancement of intercropping advantages through co-ridge intercropping of maize and peanut, we conducted a field randomized block experiment under two phosphorus levels of 0(P0) and 180 kg P2O5·hm-2(P180) with flat intercropping of maize and peanut (FIC) as the control. We analyzed the effects of co-ridge intercropping of maize and peanut (RIC) and groove-ridge intercropping of maize and peanut (GIC) on crop leaf area index (LAI), SPAD values, CO2 carboxylation ability, photosystems coordination (ΦPSⅠ/PSⅡ), and intercropping advantage of yield. The results showed that RIC significantly increased SPAD value at the silking stage of intercropping maize, and significantly improved the apparent quantum yield of photosynthesis (AQY), maximum electron transfer rate (Jmax), maximum rate of Rubisco carboxylation (Vc,max), net photosynthetic rate at the CO2 saturation (Amax) and ΦPSⅠ/PSⅡ of intercropping maize compared with those of FIC and GIC at silking stage and milking stage, but reduced the ratio of variable fluorescence Fk to amplitude Fj-Fo(Wk) and the ratio of variable fluorescence Fj to amplitude Fp-Fo(Vj) of the functional leaf photosystem Ⅱ (PSⅡ) at the milking stage of maize. There were no significant differences in these parameters between FIC and GIC. Compared with FIC, both RIC and GIC increased LAI of intercropping peanut at late growth stage and SPAD value at pod setting stage, significantly improved Vc,max, Amax, and ΦPSⅠ/PSⅡ, and reduced Wk and Vj values of intercropping peanut functional leaves at pod expanding stage. The difference in these parameters between RIC and GIC were not significant. The land equivalent ratio and intercropping advantages of RIC were higher than those of FIC and GIC. Phosphorus application could further promote Vc,max, Jmax, Amax and ΦPSⅠ/PSⅡ of intercropping maize and peanut, and significantly improve yield advantages of intercropping. The findings indicated that co-ridge intercropping could enhance CO2 carboxylation and fixation by improving photosynthetic electron transport and pho-tosystems coordination, improve the photosynthetic rate of functional leaves of maize and peanut, thus increase crop yield and intercropping advantages.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

PURPOSE: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. METHODS: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. RESULTS: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. CONCLUSION: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

The optimal percutaneous coronary intervention strategy for patients with ST-segment elevation myocardial infarction and multivessel disease: a pairwise and network meta-analysis.

Objective: To investigate the optimal percutaneous coronary intervention (PCI) strategy in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. Methods: Trials that randomized patients with STEMI and multivessel coronary artery disease to immediate multivessel PCI, staged multivessel PCI, or culprit-only PCI and prospective observational studies that investigated all-cause death were included. Random effect risk ratio (RR) and 95% confidence interval (CI) were calculated. Results: A total of 13 randomized trials with 7627 patients and 21 prospective observational studies with 60311 patients were included. In the pairwise and network meta-analysis based on randomized trials, immediate or staged multivessel PCI was associated with a lower risk of long-term major adverse cardiac events (MACE; RR: 0.58; 95% CI: 0.45 to 0.74) than culprit-only PCI, which was mainly due to lower risks of myocardial infarction (RR: 0.67; 95% CI: 0.51 to 0.88) and revascularization (RR: 0.38; 95% CI: 0.28 to 0.51), without any significant difference in all-cause death (RR: 0.85; 95% CI: 0.69 to 1.04; I 2 = 0.0%). However, short-term outcomes were deficient in randomized trials. The results from real-world prospective observational studies suggested that staged multivessel PCI reduced long-term all-cause death (RR: 0.53; 95% CI: 0.39 to 0.71; I 2 = 15.6%), whereas immediate multivessel PCI increased short-term all-cause death (RR: 1.58; 95% CI: 1.22 to 2.05; I 2 = 43.8%) relative to culprit-only PCI. Conclusion: For patients in randomized trials, multivessel PCI in an immediate or staged procedure was preferred due to improvements in long-term outcomes. As a supplement, the results in real-world patients derived from prospective observational studies suggested that staged multivessel PCI was superior to immediate multivessel PCI. Therefore, staged multivessel PCI may be the optimal PCI strategy for patients with STEMI and multivessel coronary artery disease.

Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction.

AIMS: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. METHODS AND RESULTS: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. CONCLUSION: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.

Circular RNA WHSC1 exerts oncogenic properties by regulating miR-7/TAB2 in lung cancer.

Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy.

Culprit-only versus multivessel percutaneous coronary intervention among STEMI patients complicated by cardiogenic shock in real-world practice: an updated systematic review and meta-analysis.

BACKGROUND: The recent randomized trials demonstrated that culprit-only percutaneous coronary intervention (CO-PCI) was superior to multivessel PCI (MV-PCI) among ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) complicated by cardiogenic shock, yet the real-world scenario remains to be determined. METHODS: Studies that compared CO-PCI versus MV-PCI in STEMI patients with MVD complicated by cardiogenic shock were identified by a systematic search of published articles. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by using random-effects models. RESULTS: Eventually, 18 observational studies involving 73,528 patients were included. The results showed that CO-PCI was associated with lower risks of short-term renal failure (OR: 0.75; 95% CI: 0.64 to 0.88; I2=14.7%) and short-term stroke (OR: 0.86; 95% CI: 0.77 to 0.96; I2=0.0%) compared with immediate MV-PCI. But the risk of short-term myocardial infarction (OR: 1.12; 95% CI: 1.03 to 1.22; I2=0.0%) was increased. There was no significant difference during long-term follow-up. The results remained consistent after adding the only randomized trial. DISCUSSION: Based on real-world analyses, our meta-analysis suggested that CO-PCI decreased the risks of renal failure and stroke but increased the risk of myocardial infarction relative to immediate MV-PCI during short-term follow-up in STEMI patients with MVD complicated by cardiogenic shock. If possible in clinical practice, staged MV-PCI can be given a try to decrease the risks of renal failure and stroke associated with immediate MV-PCI and myocardial infarction associated with CO-PCI. However, the conclusions need to be confirmed by further large-scale studies.

Circ_0044516 Regulates miR-136/MAT2A Pathway to Facilitate Lung Cancer Development.

Circular RNA (circRNA) is a type of noncoding RNA that can interact with miRNAs to regulate gene expression. However, little is known concerning circRNA, which is crucial in the pathogenesis of lung cancer. To date, limited studies have explored the role of circ_0044516 in lung cancer progression. Recently, we observed that circ_0044516 expression levels were obviously elevated in lung cancer tissues and cells. A549 and SPCA1 cells were transfected with circ_0044516 siRNA. We observed that knockdown of circ_0044516 dramatically repressed cell proliferation, increased cell apoptosis, and repressed the cell cycle. Moreover, A549 and SPCA1 cell migration and invasion abilities were greatly repressed by circ_0044516 siRNA. Due to accumulating evidence demonstrating the vital role of cancer stem cells, their mechanism of involvement has drawn increasing attention in tumor progression and metastasis research. We also found that cancer stem cell properties were restrained by silencing circ_0044516 in A549 and SPC-A1 cells. Moreover, in vivo xenograft experiments showed that circ_0044516 downregulation reduced tumor growth. Mechanistically, in lung cancer and using bioinformatics, we demonstrated that circ_0044516 sponges miR-136 targeting MAT2A. Furthermore, rescue assays were carried out to identify that circ_0044516 modulates cell proliferation, invasion, and stemness by regulating miR-136 and MAT2A in lung cancer. In summary, our study revealed that the circ_0044516/miR-136/MAT2A axis is involved in lung cancer progression. Our findings may provide novel targets for diagnosis and therapeutic intervention in lung cancer patients.

Impact of the shift to a fibrinolysis-first strategy on care and outcomes of patients with ST-segment-elevation myocardial infarction during the COVID-19 pandemic-The experience from the largest cardiovascular-specific centre in China.

BACKGROUND: The impact of fibrinolysis-first strategy on outcomes of patients with ST-segment-elevation myocardial infarction (STEMI) during the COVID-19 pandemic was unknown. METHODS: Data from STEMI patients presenting to Fuwai Hospital from January 23 to April 30, 2020 were compared with those during the equivalent period in 2019. The primary end-point was net adverse clinical events (NACE; a composite of death, non-fatal myocardial reinfarction, stroke, emergency revascularization, and bleeding over BARC type 3). The secondary outcome was a composite of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. RESULTS: The final analysis included 164 acute STEMI patients from 2020 and 240 from 2019. Eighteen patients (20.2% of those with indications) received fibrinolysis therapy in 2020 with a median door-to-needle time of 60.0 (43.5, 92.0) minutes. Patients in 2020 underwent primary PCI less frequently than their counterparts (14 [14.2%] vs. 144 [86.8%] in 2019, P < 0.001), and had a longer median door-to-balloon time (175 [121,213] minutes vs. 115 [83, 160] minutes in 2019, P = 0.009). Patients were more likely to undergo elective PCI (86 [52.4%] vs. 28 [11.6%] in 2019, P < 0.001). The in-hospital NACE was similar between 2020 and 2019 (14 [8.5%] vs. 25 [10.4%], P = 0.530), while more patients developed a secondary outcome in 2020 (20 [12.2%] vs. 12 [5.0%] in 2019, P = 0.009). CONCLUSIONS: The fibrinolysis-first strategy during the COVID-19 pandemic was associated with a lower rate of timely coronary reperfusion and increased rates of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. However, the in-hospital NACE remained similar to that in 2019.

CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR-21.

Acute lung injury (ALI) induced by sepsis is characterized by an inflammatory process related to the up-regulation of inflammatory cytokines and chemokines. In the present study, we explored the role of circC3P1 in sepsis-induced ALI in vitro and in vivo. The caecal ligation and puncture (CLP)-induced sepsis model was established through CLP surgery. Forty adult male C57BL/6 mice were randomly assigned into sham, CLP, CLP + vector and CLP + circC3P1 (each n = 10). Primary murine pulmonary microvascular endothelial cells (MPVECs) were transfected with circC3P1 or empty vector 24 hours prior to LPS treatment via Lipofectamine 2000. The expressions of circC3P1, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were evaluated after 6-h LPS treatment. Cell apoptosis was evaluated via flow cytometry. The CLP group demonstrated pulmonary morphological abnormalities, increased concentrations of TNF-α, IL-6 and IL-1ß in the lung tissue, compared with the sham group. MPVECs treated with LPS significantly elevated TNF-α, IL-6 and IL-1ß levels and increased cell apoptosis than that in the control group. The circC3P1 overexpression in sepsis-induced ALI mice attenuated pulmonary injury, inflammation and apoptosis. Besides, circC3P1 revealed anti-inflammatory and anti-apoptotic effect in MPVEC-treated LPS. CircC3P1 overexpression reduced cell apoptosis and pro-inflammatory cytokines levels via down-regulating miR-21. CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in ALI induced by sepsis through modulating miR-21, indicating that circC3P1 is a promising therapeutic biomarker for sepsis-induced ALI.

Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients.

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

Relations between gross motor competence and physical fitness in 3-5 years old children / 中国学校卫生

Objective@#The cross-sectional study examined associations between gross motor competence and physical fitness in 3-5 years old children.@*Methods@#A convenient sampling method was used to select 201 children aged 3-5 years, to assess gross motor competence, each child accomplished the Test of Gross Motor Development-3(TGMD-3). The level of physical fitness was measured by National Physical Fitness Test, comprising eight different tasks including height, weight, flexibility(sit-and-reach test), balance (walking on a balance beam), explosive force(Standing long jump), strength(Tennis ball throwing), agility(10-shuttle-run test), strength and coordination(Continuous foot jump).@*Results@#With the increase of age, the scores of locomotor skills，object control skills, gross motor competence, height, weight, walking on a balance beam, continuous foot jump, tennis ball throwing and standing long jump were better(P<0.01). Significant differences were not found in the gross motor competence, locomotor skills, 10-shuttle-run test, continuous foot jump, standing long jump and walking on a balance beam(P>0.05). In the object control skills and tennis ball throwing, the boys showed a greater performance(P<0.01). In the sit-and-reach test, girls showed a greater performance(P<0.01). The results revealed a significant relationship between gross motor competence and the following items: 10-shuttle-run test, continuous foot jump, standing long jump, walking on a balance beam, tennis ball throwing(P<0.05). There were no associations among gross motor competence, BMI(r=0.02), sit-and-reach test(r=0.07). There were no associations between gross motor competence and physical fitness in 3-5 years old(r=-0.13-0.21), except for 5 years old children’s object control skills and continuous foot jump(r=0.42). Sex, age, height , BMI (R2=0.05,F=2.62, P>0.05) as well as gross motor competence(△R2=0.04, F=2.00, P>0.05) did not predict physical fitness.@*Conclusion@#The results indicated a relationship between motor competence and physical fitness in 3-5 years old. In order to increase the level of physical fitness, the educators should pay attention to the development of children’s gross motor.

Experience of ZHANG Lv-fu in Preventive Treatment of Diseases in Women's Childbearing Period / 中国中医药信息杂志

In clinic, eugenics is a great demand of women in childbearing after marriage. If women have been in poor physical fitness, it can affect fertility. ZHANG Lv-fu was born in a TCM aristocratic family, and is good at the treatment of gynecology and pediatrics. It has a good curative effect when he takes differentiation regulation in the stages of before pregnancy, pregnancy, and postpartum. This article summarized the experience of ZHANG Lv-fu in using TCM for preventive treatment of diseases in different stages of women's reproductive period.

Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare form of non-small cell lung carcinoma. The current study focused on its clinicopathological features and potential factors influencing the prognosis. METHODS: The statistical analysis was based on the clinicopathological records and the prognosis of 43 LELC patients, analyzed by Kaplan-Meier method, Log-rank test, and COX regression analysis. RESULTS: The patients' average age was 57.35±9.22 years, 86.05% of them were non-smokers and 53.49% were women. The average tumor diameter was 3.24±1.57 cm. The 2- and 5-year overall survival (OS) rates of LELC patients were 90% and 74%, respectively; the disease-free survival (DFS) rates were 87% and 47%, respectively. The patients with large tumor, accompanied with lymph nodes metastasis or at the advanced stage had the worst OS, and the patients with lymph nodes metastasis or at the advanced stage had the worst DFS. Univariate analysis indicated that T and N grading and TNM stage influenced the OS, and N grading and TNM stage influenced the DFS; the independent factors affecting OS or DFS were not identified by multivariate analysis. CONCLUSIONS: LELC commonly occurred in senior non-smoking women. In summary, the prognosis of LELC was satisfactory.

VATS right upper lobectomy.

Standard thoracotomy has been considered as the classic approach and only choice for the diagnosis and treatment of certain thoracic diseases especially in patients with peripheral lung cancer. Video-assisted thoracic surgery (VATS) is a new minimally invasive thoracic surgery through small incisions in the intercostal muscle of chest wall by using modern camera technology, high-tech equipment and surgical instrument. Consequently, VATS has become the preferred main method for peripheral lung cancer in the last two decades. The aim of the present paper is to describe and discuss the operative techniques of VATS for right upper lobectomy (RUL).

Expression and significance of hypoxia inducible factor-1α and lysyl oxidase in non-small cell lung cancer.

OBJECT: To detect expression of hypoxia inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) in non-small cell lung cancer (NSCLC) and explore their roles in prognosis. METHODS: The mRNA levels of HIF-1α and LOX were investigated by real-time reverse-transcriptase polymerase chain reaction in 40 cases of tumour and paired normal tissues. In addition, protein expression of HIF-1α and LOX was examined by immunohistochemistry in 82 cases of tumour and 45 paired normal tissues. The relationship between HIF-1α or LOX and clinicopathologic characteristics, as well as the correlation between HIF-1α and LOX, were also examined. Kaplan-Meier survival curves and the log-rank test were used to analyze progression-free survival. RESULTS: HIF-1α or LOX mRNA levels in tumor tissues was significantly higher than those in paired normal tissues (p<0.01). Positive HIF-1α or LOX protein expression in tumor tissues was noted in 46/82 (56.1%) and 49/82 (59.8%) of the cases, respectively, being significantly higher than those in paired normal tissues (p<0.05). There was significant correlation between the expression of HIF-1α or LOX and tumor size, lymph node metastasis and pathological stage (p<0.05). The expression of HIF-1α and LOX had a significant inverse impact on survival of patients with NSCLC. CONCLUSION: HIF-1α and LOX may play a pivotal role in the development of NSCLC, and may act in synergy to promote the progression of NSCLC.

Association of preoperative serum IGF- I concentration with clinicopathological parameters in patients with non-small cell lung cancer.

Insulin-like growth factor-I (IGF-I) is a mitogenic and anti-apoptotic factor. Serum IGF-I concentration is related to some cancer risk and tumor progression. The aim of this research was to study the association of preoperative serum IGF-I concentration with clinicopathological parameters and prognosis of non-small cell lung cancer (NSCLC). Preoperative serum IGF-I concentration was measured in 80 consecutive patients with NSCLC who underwent radical lung cancer resection, and 45 patients with benign pulmonary lesion (BPL) by using enzyme linked immunosorbent assay (ELISA). The results showed that the serum IGF-I concentration was elevated and correlated with clinicopathological parameters and overall survival (OS) in NSCLC patients. Serum IGF-I concentration was significantly higher in patients with NSCLC than in those with BPL. The IGF-I concentrations were significantly higher in NSCLC patients with ≥T2, N1-3, and in IIIA-IV but not in those with