Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.

High 28-day mortality in critically ill patients with sepsis and concomitant active cancer.

OBJECTIVE: This study was performed to explore the characteristics and outcomes of patients with sepsis accompanied by active cancer who were admitted to the intensive care unit (ICU). METHODS: The baseline characteristics, infection profiles, and outcomes of patients with sepsis were retrospectively analyzed according to the presence of concomitant active cancer. The association between concomitant active cancer and 28-day mortality was explored. RESULTS: Of 23,956 patients with sepsis, 1574 (6.6%) had concomitant active cancer. The most common type was digestive (30.7%). The 28-day mortality ranged from 41.9% to 81.5%. Patients with active cancer had a significantly higher Simplified Acute Physiology Score II and significantly shorter length of ICU stay. Respiratory (32.9%), genitourinary (31.0%), and bloodstream (17.0%) infections were most common. Escherichia coli was the most frequent gram-negative pathogenic bacteria. The 28-day mortality rate was significantly higher in patients with than without active cancer. Concomitant active cancer was associated with increased 28-day mortality in patients with sepsis. Hematological malignancy was associated with a significantly higher risk of death than solid tumors. CONCLUSIONS: Concomitant active cancer was associated with higher 28-day mortality in patients with sepsis requiring ICU admission. Hematological malignancy was associated with a higher risk of death than solid tumors.

High Serum Iron level is Associated with Increased Mortality in Patients with Sepsis.

Iron is an essential nutrient for bacterial survival and thus higher iron levels may precipitate bacterial infections. We investigated the association between the serum iron level and prognosis in patients with sepsis by using the single-centre Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis patients with iron parameters measured on ICU admission were included and stratified according to quartiles of serum iron levels. A total of 1,891 patients diagnosed with sepsis according to the Sepsis-3 criteria were included in this study, 324 of whom were septic shock. After adjusting for confounding variables, higher iron quartile was associated with an increase in 90-day mortality in the Cox regression analysis. Moreover, a stepwise increase in the risk of 90-day mortality was observed as the quartiles of serum iron levels increased in the patients with sepsis. In conclusion, higher serum iron levels were independently associated with increased 90-day mortality in this large cohort of patients with sepsis.

Clinical and microbiological characteristics of Klebsiella pneumoniae liver abscess in East China.

BACKGROUND: Klebsiella pneumoniae has been the dominant pathogen for liver abscesses in several Asian countries. Although the prevalence of K. pneumoniae liver abscess (KLA) in mainland China is increasing recently, the clinical and microbiological characteristics of KLA in China have not been elucidated. METHODS: Clinical and microbiology characteristics of 45 consecutive patients with KLA from a tertiary teaching hospital in China between June 2008 and June 2012 were retrospectively evaluated. RESULTS: Vast majority of the strains were susceptible to main antimicrobial agents. Most of K. pneumoniae strains from pyogenic liver abscess patients belonged to K1/K2 serotype (68.9% for K1 serotype and 20% for K2 serotype). All K. pneumoniae strains were rmpA positive, and 68.9% of these strains were magA positive. Overall, 57.8% (26/45) of K. pneumoniae strains belonged to ST23. Twenty-five of 26 ST23 K. pneumoniae isolates (96.2%) from KLA patients were magA-positive and K1 serotype. Only 28.9% (13/45) of KLA isolates exhibited hypermucoviscous phenotype, which is clinically used as the characteristic of hypervirulent K. pneumoniae (hvKP). Liver abscess sizes in patients infected with hvKP were tend to be larger than those in patients infected with cKP. There was no significant association between the microbiological and clinical characteristics including serotypes, magA and rmpA genotypes, and STs with the metastatic infection and prognosis of KLA. CONCLUSIONS: Neither the serotypes, magA and rmpA genotypes, nor the STs of K. pneumoniae were associated with the metastatic infection and prognosis of KLA. However, further studies with larger sample are needed in the future.

Antihypertensive therapy with nicardipine for patients with aortic disease is associated with more esmolol usage than urapidil.

BACKGROUND: Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous ß-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients' outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease. METHODS: All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients' outcomes were evaluated with logistics regression. RESULTS: A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine (with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123). CONCLUSIONS: Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.

Aortoduodenal fistula following aortic reconstruction of a pseudoaneurysm caused by stab wound 12 years ago.

Gastrointestinal bleeding due to aortoenteric fistula is extremely rare. Aortoenteric fistula is difficult to be diagnosed timely and entails a significant morbidity and mortality. Herein, we present an uncommon case of gastrointestinal bleeding caused by aortoduodenal fistula, which was a complication of a successful aortic reconstruction 4 months ago for an aortic pseudoaneurysm resulted from a stab wound 12 years ago. An urgent laparotomy confirmed an aortoduodenal fistula and repaired the defects in aorta and duodenum, but a prolonged shock led to the patient's death. In summary, early diagnosis and surgical intervention for aortoenteric fistula are vital for survival.