Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats

Objective

We hypothesized that pretreatment with sivelestat therapy could attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat model.

Methods

The neutrophil elastase inhibitor was administered intraperitoneally 30 min before and at the initiation of ventilation. The rats were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV) early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI scores were investigated.

Results

The ratio of wet-to-dry weight, BALF neutrophil and protein, tissue MDA and VILI scores were significantly increased in the VILI group compared to the sham group [3.85±0.32 vs. 9.05±1.02, P<0.001; (0.89±0.93)×10⁴ vs. (7.67±1.41)×10⁴ cells/mL, P<0.001; 2.34±0.47 vs. 23.01±3.96 mg/mL, P<0.001; 14.43±1.01 vs. 36.56±5.45 nmol/mg protein, P<0.001; 3.78±0.67 vs. 7.00±1.41, P<0.001]. This increase was attenuated in the early sivelestat group compared with the sivelestat group [wet-to-dry ratio: 6.76±2.01 vs. 7.39±0.32, P=0.032; BALF neutrophil: (5.56±1.13)×10⁴ vs. (3.89±1.05)×10⁴ cells/mL, P=0.021; BALF protein: 15.57±2.32 vs. 18.38±2.00 mg/mL, P=0.024; tissue MDA: 29.16±3.01 vs. 26.31±2.58, P=0.049; VILI scores: 6.33±1.41 vs. 5.00±0.50, P=0.024].

Conclusions

Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.     

Higher level of heme oxygenase-1 in patients with stroke than TIA

Background

There is a reverse relationship between serum bilirubin level and incidence of stroke, heme oxygenase-1 (HO-1) can catalyze heme into bilirubin, it is unknown the association of HO-1 level with risk of stroke.

Methods

Sixty patients with stroke and fifty patients with transient ischemic attack (TIA) were recruited. Serum level of HO-1, total and direct bilirubin, alanine transaminase, live function, lipid profile and infection status of patients were measured.

Results

Significant differences were found between two groups in terms of serum levels of HO-1 (163.6±58.7 vs. 141.2±49.7, P=0.032), total bilirubin (10.1±4.6 vs. 15.8±2.7, P<0.001), direct bilirubin (3.2±2.1 vs. 5.9±1.2, P<0.001), fasting glucose (6.7±3.1 vs. 4.9±1.3, P<0.001), cholesterol (4.4±1.1 vs. 3.9±0.8, P=0.005) and diastolic blood pressure (DBP) (84.9±9.4 vs. 81.3±9.2, P=0.046). In multivariate analysis, serum direct bilirubin (OR, 2.83; P<0.001), total bilirubin (OR, 1.82, P=0.001), DBP (OR, 0.88, P=0.041), and fasting glucose (OR, 0.34, P<0.001) were independent predictors of stroke.

Conclusions

Serum HO-1 level is higher in patients with stroke than TIA, but the bilirubin level is lower in patients with stroke than TIA and is an independent predictor of stroke. Further studies are warranted to clarify the underlying link among HO-1, bilirubin and stroke.     

Comparative study of systematic thoracoscopic lymphadenectomy and conventional thoracotomy in resectable non-small cell lung cancer

Objective

To assess the feasibility and safety of the video-assisted thoracoscopy surgery (VATS) systematic lymph node dissection in resectable non-small cell lung cancer (NSCLC).

Methods

The clinical data of patients with NSCLC who underwent VATS or thoracotomy combined with lobectomy and systematic lymphadenectomy from January 2001 to January 2008 were retrospectively analyzed to identify their demographic parameters, number of dissected lymph nodes and postoperative complications.

Results

A total of 5,620 patients were enrolled in this study, with 2,703 in the VATS group, including 1,742 men (64.4%), and 961 women (35.6%), aged 59.5±10.9 years; and 2,917 in the thoracotomy group, including 2,163 men (74.2%), and 754 women (25.8%), aged 58.5±10.4 years. Comparing the VATS with the thoracotomy groups, the mean operative time was 146 vs. 157 min, with a significant difference (P<0.001); and the average blood loss was 162 vs. 267 mL, with a significant difference (P<0.001). Comparing the two groups of patients data, the number of lymph node dissection: 18.03 in the VATS group and 15.07 in the thoracotomy group on average, with a significant difference (P<0.001); postoperative drainage time: 4.5 days in the VATS group and 6.37 days in the thoracotomy group on average, with a significant difference (P<0.001); postoperative hospital stay: 6.5 days in the VATS group and 8.37 days in the thoracotomy group on average, with a significant difference (P<0.001); proportion of postoperative chylothorax: 0.2% (4/2,579) in the VATS group and 0.4% (10/2,799) in the thoracotomy group, without significant difference (P>0.05).

Conclusions

For patients with resectable NSCLC, VATS systematic lymph node dissection is safe and effective with fewer postoperative complications, and significantly faster postoperative recovery compared with traditional open chest surgery.     

Intestinal barrier dysfunction is involved in the development of systemic inflammatory responses and lung injury in type A aortic dissection: a case-control study

BackgroundThe definite pathogenesis of lung injury complicated by type A aortic dissection (TAAD) remains unclear. In this paper, we investigated the relationship between intestinal injury, lung injury, and systemic inflammatory responses, with the aim of exploring the mechanism underlying intestinal injury and its impact on systemic inflammatory responses and lung injury in patients with TAAD.MethodsPatients with TAAD (n=36) and those with aortic root aneurysm (ARA) (n=30) were compared. TAAD patients were younger and had higher creatinine (Cr) than ARA patients. White blood cell (WBC) count, neutrophil count, neutrophil percentage, interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), histamine (HIS) levels, PaO₂-FiO₂ ratio, diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), and peptidoglycan (PGN) were measured using the same laboratory methods between the two groups.ResultsIncreased WBC [(9.70±4.05)×10⁹/L vs. (5.88±1.2)×10⁹/L, P<0.001], neutrophil [(7.65±4.27)×10⁹/L vs. (3.40±0.97)×10⁹/L, P<0.001], neutrophil percentage [(74.73±13.42)% vs. (57.67±9.45)%, P<0.001], IL-6 (37.48±4.87 vs. 20.90±0.92 pg/mL, P<0.001), IL-8 (97.15±9.11 vs. 69.46±3.17 pg/mL, P<0.001), TNF-α (71.32±10.35 vs. 33.90±2.27 pg/mL, P<0.001), CRP (10.67±1.62 vs. 4.43±0.26 µg/mL, P<0.001), HIS (13.29±1.88 vs. 7.63±0.58 ng/mL, P<0.001), DAO (24.94±4.72 vs. 10.92±2.44 U/L, P<0.001), iFABP (879.01±190.12 vs. 206.35±42.20 pg/mL, P<0.001), and PGN (31.10±5.51 vs. 12.52±2.20 ng/mL, P<0.001) and decreased PaO₂-FiO₂ ratio (365.35±146.47 vs. 447.86±70.80 mmHg, P=0.01) were detected in TAAD group relative to ARA group. In TAAD group, positive correlations were detected between DAO and inflammatory cytokines [IL-6 (r=0.56, P<0.001), IL-8 (r=0.61, P<0.001), TNF-α (r=0.71, P<0.001), and CRP (r=0.68, P<0.001)], between iFABP and inflammatory cytokines [IL-6 (r=0.72, P<0.001), IL-8 (r=0.71, P<0.001), TNF-α (r=0.90, P<0.001), and CRP (r=0.89, P<0.001)], between DAO and PGN (r=0.52, P<0.001), between iFABP and PGN (r=0.74, P<0.001), between PGN and inflammatory cytokines [IL-6 (r=0.85, P<0.001), IL-8 (r=0.44, P<0.001), TNF-α (r=0.61, P<0.001), and CRP (r=0.73, P<0.001)]. In acute TAAD subgroup, PGN and PaO₂-FiO₂ ratio were negatively correlated (r=−0.50, P=0.036).ConclusionsSystemic inflammatory responses in TAAD patients may lead to lung and intestine injury, and the latter may be involved in the development of systemic inflammatory responses and lung injury in these patients.     

Severe intraoperative complications during VATS Lobectomy compared with thoracotomy lobectomy for early stage non-small cell lung cancer

Background

Video-assisted thoracic surgery (VATS) lobectomy has been proved to have shorter hospital stay, less perioperative complications and less pain compared with lobectomy by thoracotomy, but severe intraoperative complications during VATS lobectomy is rare reported. We compared intraoperative safety between VATS lobectomy and lobectomy by thoracotomy.

Methods

659 patients with postoperative stage I and IIa non-small cell lung cancer (NSCLC) who underwent lobectomy in China-Japan Friendship Hospital from February 2008 to June 2012 were analyzed retrospectively, in which 277 were performed by thoracotomy, 357 performed by VATS, and 25 performed by VATS converted to open. Outcomes were analyzed to compare the incidence of significant bleeding, with conversion cases were included into VATS group.

Results

Ten severe intraoperative complications were identified in 10 patients (6 in VATS, 4 in open), with no intraoperative deaths. The incidence of severe intraoperative complications was similar between VATS group and thoracotomy group [1.57% (6/382) vs. 1.44% (4/277), P=1.0]. Most severe intraoperative complications were related to the injury of major pulmonary vessels (9/10), and most of these complications occurred during upper lobectomy (8/10). There was no statistically significant difference in blood loss (242.85±220.47 vs. 240.43±144.36, P=0.865), and operative time (198.00±75.24 vs. 208.05±61.97, P=0.061) between the open and VATS groups, respectively, but blood loss and operative time are significant different after elimination of conversion cases (214.34±151.85 vs. 240.43±144.36, P<0.01; 193.24±72.64 vs. 208.05±61.97, P<0.01).

Conclusions

Our preliminary study demonstrated that the incidence of severe intraoperative complication during VATS lobectomy was low and similar to open lobectomy. The severe intraoperative complications during VATS lobectomy are manageable and the surgeons need to take proper caution in performing VATS lobectomy.KEY WORDS : Lung cancer surgery, lobectomy, bleeding, surgery complications     

Comparison of outcomes of open and minimally invasive esophagectomy in 183 patients with cancer

Background and objectives

Only few randomized trials or comparative studies with large number of patients have been reported on the outcomes of thoracoscopic and laparoscopic esophagectomy (TLE) with cervical anastomosis and open 3-field esophagectomy (OE) for patients with esophageal cancer. The objective of this study is to compare the safety, feasibility, and short-term outcomes between TLE and OE (via right throax, abdomen, and left neck) for esophageal cancer.

Methods

Clinical and surgical data of patients with esophageal cancer who underwent either TLE or OE between February 2011 and December 2013 were retrospectively analyzed. Demographic characteristics, pathological data, operative procedures, and intraoperative and postoperative outcomes and survival in patients were compared between both groups.

Results

Of the 183 patients included in this retrospective analysis, 94 underwent TLE and 89 underwent OE. Demographics, pathologic data, inpatient mortality, and overall surgical morbidity in both cohorts were almost identical. A significant difference was observed in blood loss (182.6±78.3 vs. 261.4±87.2 mL, P<0.001), hospital stay (13.9±7.5 vs. 17.1±10.2 days, P=0.017), overall surgical morbidity (25.5% vs. 46.1%, P=0.004), and rate of pulmonary and cardiac complication (9.6% vs. 27.0%, P=0.002; 4.1% vs. 12.4%, P=0.046) between TLE and OE groups; however, no difference in survival period was observed between the groups.

Conclusions

The procedure of TLE for esophageal cancer possesses advantages in intraoperative and postoperative outcomes compared with OE. The TLE procedure results in similar or potentially better outcomes.     

Initial synchronized intermittent mandatory ventilation versus assist/control ventilation in treatment of moderate acute respiratory distress syndrome: a prospective randomized controlled trial

Background

Assist/control (A/C) ventilation may induce delirium in patients with acute respiratory distress syndrome (ARDS). We conducted a trial to determine whether initial synchronized intermittent mandatory ventilation with pressure support (SIMV + PS) could improve clinical outcomes in these patients.

Methods

Intubated patients with moderate ARDS were enrolled and we compared SIMV + PS with A/C. Identical sedation, analgesia and ventilation strategies were performed. The co-primary outcomes were early (≤72 h) partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) and incidence of delirium. The secondary outcomes were all-cause in-hospital mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, and duration of mechanical ventilation and hospital stay.

Results

We screened 2,684 patients and 40 patients were enrolled in our study. In SIMV + PS, early (≤72 h) PaO₂/FiO₂ was greater improved than that at baseline and that in A/C (P<0.05) with lower positive end-expiratory pressure (PEEP) (8.7±3.0 vs. 10.3±3.2, P<0.001) and FiO₂ (58%±18% vs. 67%±19%, P<0.001). We found more SIMV + PS success (defined as SIMV + PS successfully applied without switching to A/C) (100.0% vs. 16.7%, P<0.001), less male (46.3% vs. 85.7%, P=0.015) and pulmonary etiology of ARDS (53.8% vs. 92.9%, P=0.015), and lower PEEP (9.1±3.1 vs. 10.3±3.3, P=0.004) and FiO₂ (58%±19% vs. 71%±19%, P<0.001) in survival patients. However, there were no significant differences in incidence of delirium and mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, duration of mechanical ventilation and hospital stay (P>0.05).

Conclusions

In patients with moderate ARDS, SIMV + PS can safely and effectively improve oxygenation, but does not decrease mortality, incidence of delirium and patient-ventilator asynchrony, dosages of analgesics and sedatives, and duration of mechanical ventilation and hospital stay.     

Increased QT dispersion and P wave dispersion in major depressive disorder

BACKGROUND:

QT and P wave dispersion parameters can indicate abnormalities in autonomic nervous system and cardiac functioning.

OBJECTIVES:

To determine QT and P wave dispersion in patients with major depressive disorder compared with healthy volunteers.

METHODS:

Fifty newly diagnosed patients with major depressive disorder and 50 age- and sex-matched healthy volunteers underwent 12-lead electrocardiography. QT interval, QT dispersion, heart rate-corrected QT dispersion and P wave dispersions were calculated manually by a blinded specialist.

RESULTS:

Groups were comparable in terms of age, sex, body mass index, smoking status, metabolic diseases and left ventricular ejection fraction. The major depressive disorder group had significantly higher QT dispersion (58.5±9.9 versus 41.7±3.8; P<0.001), heart rate-corrected QT dispersion (62.5±10.0 versus 45.2±4.3; P<0.001) and P wave dispersion (46.9±4.8 versus 41.5±5.1; P<0.001).

CONCLUSION:

Increased QT dispersion, heart-rate corrected QT dispersion and P wave dispersion in major depressive disorder patients may be indicative of autonomic imbalance and increased risk of cardiac morbidity and mortality.     

Linking soluble vascular adhesion molecule-1 level to calcific aortic stenosis in patients with coronary artery disease

BACKGROUND:

Calcific aortic stenosis (AS) is an atherosclerosis-related process and the most common cause of valve disease requiring surgery.

OBJECTIVE:

To assess the association of inflammatory markers with AS in advanced atherosclerosis.

METHODS:

Consecutive patients with coronary artery disease (CAD) associated with AS were prospectively identified (mean transvalvular aortic gradient of 30 mmHg or greater). Subjects with aortic sclerosis (mean transvalvular aortic gradient of 10 mmHg or less) served as controls. All patients underwent clinical evaluation, echocardiography and coronary angiography.

RESULTS:

One hundred twenty-two patients with AS (85 men) and 101 with aortic sclerosis (76 men) of similar CAD severity were enrolled. The AS patients were older (mean [± SD] 71±7 years versus 66±7 years; P<0.001), had higher soluble vascular adhesion molecule-1 (s-VCAM-1) levels (1533±650 μg/L versus 1157±507 μg/L; P<0.001), but lower soluble intercellular adhesion molecule-1 (s-ICAM-1) (254±81 μg/L versus 293±84 μg/L; P<0.01) and soluble E-selectin (53±28 μg/L versus 62±29 μg/L; P<0.05) levels. The two groups did not differ with respect to C-reactive protein level (3±2.9 mg/L versus 3.4±2.6 mg/L; P not significant). Higher s-VCAM-1 (OR 1.09, 95% CI 1.04 to 1.14; P<0.001) and lower s-ICAM-1 (OR 0.82, 95% CI 0.72 to 0.94; P<0.001) levels were associated with AS after adjustment for age.

CONCLUSION:

Increased s-VCAM-1 levels were associated with calcific AS in patients with significant CAD.     

Vaspin and lipocalin-2 levels in severe obsructive sleep apnea

Background

Vaspin and lipocalin-2 are less-known recent members of adipocytokine family. There are ongoing studies investigating the role of vaspin ve lipocalin-2 in metabolic syndrome (MS). Obstructive sleep apnea syndrome (OSAS) is independently associated with an increased prevalence of MS. We aimed to measure the levels of vaspin and lipocalin-2 which are secreted from adipocytes in patients with severe OSAS and examine the relationship between these two adipocytokines and OSAS.

Methods

The study consisted of two groups: severe OSAS patients with an apnea-hypopnea index (AHI) of >30/h (OSAS group, 34 subjects) and age-matched healthy volunteers with a AHI <5/h (control group, 25 subjects) Serum levels of vaspin and lipocalin-2 in these two groups were compared.

Results

Serum levels of vaspin were significantly lower in OSAS group; patients with severe OSAS compared with control group; healthy volunteers (OSAS group: 0.69±0.5 vs. control group: 1.24±1.13; P=0.034). The difference between the two groups in terms of serum levels of lipocalin-2 has not reached statistical significance (OSAS group: 61.6±18.2 vs. control group: 68.5±20.1; P=0.17).

Conclusions

We found that serum vaspin levels were significantly lower in patients with severe OSAS compared with healthy controls. Lipocalin-2 levels were similar. The decrease in serum vaspin levels in severe OSAS patients may be important in diagnosis and follow-up of these patients.     

Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich,Switzerland

Background

The aim of this study was to investigate the impact of the introduction of a Patient Blood Management (PBM) programme in elective orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass loss, and transfusion.

Materials and methods

Orthopaedic operations (hip, n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were analysed. Period 1 (2008), was before the introduction of the PBM programme and period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative anaemia, RBC mass loss, and transfusion rates in the two periods were compared.

Results

In hip surgery, the percentage of patients with immediate pre-operative anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged, being 626±434 vs 635±450 mL (p=0.974). Transfusion rate was significantly reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre-operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss reduced from 573±355 to 476±365 mL (p<0.001). The transfusion rate dropped from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53±1.27 to 0.16±0.90 units (p<0.001). In spine surgery the prevalence of immediate pre-operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551±421 to 404±337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6% (p<0.001) and RBC transfusions decreased from 0.66±1.80 to 0.22±0.89 units (p=0.008).

Discussion

Detection and treatment of pre-operative anaemia, meticulous surgical technique, optimal surgical blood-saving techniques, and standardised transfusion triggers in the context of PBM programme resulted in a lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss, and a lower transfusion rate.     

Impacts of anemia on 3-year ischemic events in patients undergoing percutaneous coronary intervention: a propensity-matched study

Background

Anemia correlates with worse outcomes in patients undergoing percutaneous coronary intervention (PCI), improved anemia can improve the outcomes in patients who underwent PCI. But the influence of anemia on long-term ischemic events after PCI remains unknown.

Methods

We analyzed 8,825 consecutive patients who underwent PCI at General Hospital of Shenyang Military Region and identified 581 patients with anemia. Patients (anemia vs. no anemia) were compared using a propensity score analysis to best match between groups. The main outcome of this study is 3-year ischemic events after PCI, the secondary outcome of this study is 3-year mortality and major adverse cardiac events (MACE) after PCI.

Results

Compared with nonanemic patients, anemic patients were often female (38.90% vs. 14.51%) and elder patients (66.44% vs. 34.95%). Anemic patients have lower left ventricular ejection fraction (LVEF) and creatinine clearance (Ccr) and were more likely to have history of cardiovascular and cerebrovascular diseases, hypertension, peripheral vascular diseases (PVD) (P<0.05). However, the prevalences of diabetes and hyperlipidemia were lower in anemic patients (P<0.01). Anemia was an independent predictor for 3-year ischemic events [hazard ratio (HR): 2.20, 95% confidence intervals (CI): 1.61-3.00, P<0.01], 3-year mortality (HR: 3.58, 95% CI: 1.75-7.32, P<0.01) and 3-year MACE (HR: 2.14, 95% CI: 1.64-2.79, P<0.01) after PCI in post-match samples. The incidence of 3-year ischemic events was 41.0% and 19.3% in anemic and nonanemic patients, respectively.

Conclusions

Anemia is an independent predictor for 3-year ischemic events, 3-year mortality and 3-year MACE in patients who underwent PCI. Further studies need to explore the impact of the pathogenesis and progress, prevention and therapy of anemia on the outcome of patients undergoing PCI.     

TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity

AIM: To investigate the roles of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB on cystathionine β synthetase (CBS) expression and visceral hypersensitivity in rats.METHODS: This study used 1-7-wk-old male Sprague-Dawley rats. Western blot analysis was employed to measure the expression of TLR4, NF-κB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia (DRG) from control and “irritable bowel syndrome” rats induced by neonatal colonic inflammation (NCI). Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques. Immunofluorescence was employed to determine the co-expression of TLR4, NF-κB and CBS in DiI-labeled DRG neurons.RESULTS: NCI significantly upregulated the expression of TLR4 in colon-related DRGs (0.34 ± 0.12 vs 0.72 ± 0.02 for the control and NCI groups, respectively, P < 0.05). Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats. CLI-095 treatment also markedly reversed the hyperexcitability of colon-specific DRG neurons and reduced the expression of CBS (1.7 ± 0.1 vs 1.1 ± 0.04, P < 0.05) and of the NF-κB subunit p65 (0.8 ± 0.1 vs 0.5 ± 0.1, P < 0.05). Furthermore, the NF-κB-selective inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the upregulation of CBS (1.0 ± 0.1 vs 0.6 ± 0.1, P < 0.05) and attenuated visceral hypersensitivity in the NCI rats. In vitro, incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65 (control vs 8 h: 0.9 ± 0.1 vs 1.3 ± 0.1; control vs 12 h: 0.9 ± 0.1 vs 1.3 ± 0.1, P < 0.05; control vs 24 h: 0.9 ± 0.1 vs 1.6 ± 0.1, P < 0.01) and CBS (control vs 12 h: 1.0 ± 0.1 vs 2.2 ± 0.4; control vs 24 h: 1.0 ± 0.1 vs 2.6 ± 0.1, P < 0.05), whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression (1.2 ± 0.1 vs 0.6 ± 0.0, P < 0.01).CONCLUSION: Our results suggest that the activation of TLR4 by NCI upregulates CBS expression, which is mediated by the NF-κB signaling pathway, thus contributing to visceral hypersensitivity.     

Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients

Background

Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases.

Methods

Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival.

Results

PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ²=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ²=20.486, P<0.001).

Conclusions

Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.     

Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension

Objective

To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs.

Methods

AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated.

Results

A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG.

Conclusions

AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD.     

Correlations between brachial endothelial function and cardiovascular risk factors: a survey of 2,511 Chinese subjects

Objective

We examined the relationship of several cardiovascular risk factors (CVRF) to brachial artery flow-mediated dilatation (FMD) in Chinese subjects.

Methods

This was a cross-sectional study. In 2,511 Chinese adults (age 46.86±9.52 years, 1,891 men and 620 women) recruited from people who underwent health screening at The Third Xiangya Hospital, patients’ CVRF [age, body mass index (BMI), waist circumference (WC), blood pressure (BP), cholesterol parameters, creatinine (Cr), uric acid (UA), glucose level and smoking] and prevalence of present disease (hypertension, diabetes mellitus, coronary heart disease and hyperlipidemia) were investigated.

Results

Multivariate analysis revealed that FMD negative correlated with age (β=–0.29, P<0.001), gender (β=–0.12, P<0.001), BMI (β=–0.12, P=0.001), WC (β=–0.10, P=0.011), systolic BP (SBP) (β=–0.12, P<0.001), fasting glucose (β=–0.04, P=0.009), total cholesterol (TC) (β=–0.04, P=0.014), smoking (β=–0.05, P=0.003), and baseline brachial artery diameter (β=–0.35, P<0.001). FMD decreased with increasing age in both genders. In women, FMD was higher than men and age-related decline in FMD was steepest after age 40; FMD was similar in men above 55 years old.

Conclusions

In Chinese subjects, FMD may be a usefully marker of CVRF. Age, gender, BMI, WC, SBP, fasting glucose, TC, smoking, and baseline brachial artery diameter were independent variables related to the impairment of FMD. The influence of CVRF on endothelial function is more in women than men.     

Intermediate-term mortality and incidence of ICD therapy in octogenarians after cardiac resynchronization therapy

Background Clinical outcomes of cardiac resynchronization therapy （CRT） in patients over the age of 80 have not been well de-scribed.MethodsWe retrospectively identified 96 consecutive patients≥ 80 years old who underwent an initial implant or an upgrade to CRT, with or without defibrillator （CRT-Dvs. CRT-P）, at our institution between January 2003 and July 2008. The control cohort consisted of 177 randomly selected patients 〈 80 years old undergoing CRT implant during the same time period. The primary efficacy endpoint was all-cause mortality at 36 months, assessed by Kaplan-Meier time to first event curves.Results In the octogenarian cohort, mean age at CRT implant was 83.1 ± 2.9 yearsvs. 60.1 ± 8.8 years among controls （P 〈 0.001）. Across both groups, 70% were male, mean left ventricular ejection fraction （LVEF） was 24.8% ± 14.1% and QRS duration was 154 ± 24.8 ms, without significant differences between groups. Octo-genarians were more likely to have ischemic cardiomyopathy （74%vs. 37%,P 〈 0.001） and more likely to undergo upgrade to CRT instead of an initial implant （42%vs. 19%,P 〈 0.001）. The rate of appropriate defibrillator shocks was lower among octogenarians （14%vs. 27%,P = 0.02） whereas the rate of inappropriate shocks was similar （3%vs. 6%,P = 0.55）. At 36 months, there was no significant difference in the rate of all-cause mortality between octogenarians （11%） and controls （8%,P = 0.381）.ConclusionAppropriately selected octogenarians who are candidates for CRT have similar intermediate-term mortality compared to younger patients receiving CRT.     

The relationship between hypertension and anxiety or depression in Hong Kong Chinese

BACKGROUND:

Psychosocial stress can be the cause or the consequence of hypertension.

OBJECTIVE:

To study the association between hypertension and anxiety or depression in adults from Hong Kong, China.

SUBJECTS AND METHODS:

Patients with diagnosed hypertension (n=197) were recruited to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire. The control group comprised 182 normotensive subjects recruited using random telephone numbers.

RESULTS:

The score in the anxiety subscale (HADS-A) of the HADS correlated with age (r= −0.23, P<0.001) and sex (r=0.11, P=0.042), and was found to be higher in women. The score in the depression subscale (HADS-D) correlated with age (r=0.17, P=0.003) and hypertension (r=0.12, P=0.039), but not with sex (r=0.02, P=0.68). When the control subjects were matched for sex and age with the subjects with hypertension, the mean HADS-A score was 5.51±0.41 in 113 hypertensive subjects and 4.38±0.39 in 113 normotensive subjects (P=0.047). The mean HADS-D score was 5.56±0.39 in the hypertensive and 4.76±0.32 in the normotensive subjects (P=0.11). Multiple regression analysis using data from both groups indicated that the HADS-A score was related to the HADS-D score (β=0.49, P<0.001), age (β= −0.25, P<0.001) and sex (β=0.12, P=0.01) (R²=0.28), whereas the HADS-D score was related to the HADS-A score (β=0.48, P<0.001), age (β=0.30, P<0.001), positive smoking status (β=0.13, P=0.004) and lack of exercise habit (β=0.12, P=0.008) (R²=0.31). Hypertension was related to waist circumference, history of parental hypertension and age (R²=0.38, P<0.001). Anxiety and depression scores were rejected as independent variables.

CONCLUSIONS:

Hypertension was associated with anxiety but not depression; however, age, history of parental hypertension and central obesity appeared to have a stronger association with hypertension in adults from Hong Kong.     

A novel method for lymphadenectomy along the left laryngeal recurrent nerve during thoracoscopic esophagectomy for esophageal carcinoma

Background

Due to limited space in the left upper mediastinum, complete dissection of lymph nodes (LN) along left recurrent laryngeal nerve (RLN) is difficult. We herein present a novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone position for esophageal carcinoma. The method, suspension the esophagus and push aside trachea, allows en bloc lymphadenectomy along the left RLN from the below aortic arch to the thoracic inlet.

Methods

Between September 2014 and September 2015, a total of 110 consecutive patients with esophageal carcinoma were treated with thoraco-laparoscopic esophagectomy with cervical anastomosis in the semi-prone position. Outcomes between those who received surgery with the novel method and conventional surgery were compared.

Results

Fifty patients underwent the novel method and sixty received conventional surgery. The operative field around the left RLN was easier to explore with the novel method. The estimated blood loss was less (23.7±8.2 vs. 34.2±10.3 g, P=0.001), and the number of harvested LNs along the left RLN was greater (6.4±3.2 vs. 4.1±2.8 min, P=0.028) in the novel method group, while the duration of lymphadenectomy along left RLN was longer in the novel method group (28.2±3.9 vs. 20.3±2.8 min, P=0.005). The rate of hoarseness in the novel and conventional groups was 10% and 16.7%, respectively. No significant difference in postoperative morbidity related to the left RLN was noted between the groups.

Conclusions

The novel method during semi-prone esophagectomy for esophageal carcinoma is associated with better surgeon ergonomics and operative exposure.