Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function.

BACKGROUND AND AIM: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans. METHODS: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry. RESULTS: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0-15.8, n = 10) than in normal esophageal motility (13.3, 12.8-14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0-14.1, n = 10) and normal esophageal motility (13.3, 12.8-14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure. CONCLUSIONS: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs.

Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body.

Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM. In CSM, contraction occurred at trypsin concentrations of 100nM and relaxation at 1µM. A proteinase-activated receptor (PAR)2 activating peptide, SLIGKV-NH2 (1mM), induced a monophasic contraction. Those responses were unaffected by tetrodotoxin though abolished by the gap junction uncouplers carbenoxolone and octanol. They were also partially inhibited by a transient receptor potential vanilloid type 1 (TRPV1) antagonist and abolished by combination of neurokinin receptor 1 (NK1) and NK2 antagonists, but not by an NK3 antagonist, suggesting a PAR2-TRPV1-substance P pathway in sensory neurons. Substance P (100nM), an agonist for various NK receptors (NK1, NK2 and NK3) with differing affinities, induced significant contraction in CSM, but not in LSM. The contraction was also blocked by the combination of NK1 and NK2 antagonists, but not by the NK3 antagonist. Moreover, substance P-induced contractions were unaffected by the TRPV1 antagonist, but inhibited by a gap junction uncoupler. In conclusion, trypsin induced a biphasic response only in CSM and this was mediated by PAR2, TRPV1 and NK1/2. Gap junctions were indispensable in this tachykinin-induced response.

The value of assessing femoral vein to femoral artery ratio in the treatment of patients with heart failure / 中华心血管病杂志

Objective@#To investigate the relationship between ultrasound derived ratio of femoral vein to femoral artery diameter and hemodynamics in patients with heart failure.@*Methods@#This was a case-control study. A total of 61 patients with heart failure and 49 patients with non-heart failure hospitalized in the Department of Critical Care Medicine from September 2017 to September 2018 were included in this study. Doppler ultrasound was used to measure the femoral artery and vein diameter. After deep inhalation, the femoral vein diameter was measured again, and the ratio of femoral vein and artery diameter was calculated. The central venous pressure (CVP) and mean pulmonary wedge pressure (mPAWP) were also measured. Pearson correlation analysis was used to explore the correlation between the ratio of femoral vein diameter to femoral artery diameter and CVP and mPAWP, and linear regression equation was established.@*Results@#The overall CVP and mPAWP levels were significantly higher, and the femoral vein diameter after deep inhalation was bigger in heart failure patients than in non-heart failure patients(all P<0.001). The femoral vein diameter/femoral artery diameter ratio was positively correlated with CVP (r=0.76, P<0.001), and positively correlated with mPAWP (r=0.40, P<0.001) in heart failure group. The linear regression equation established by the femoral vein/femoral artery diameter ratio and CVP in the heart failure group showed that the inner diameter of the femoral vein/the inner diameter of the femoral artery ratio≥1.3 corresponded CVP≥15.518 cmH2O(1 cmH2O=0.098 kPa) in heart failure patients.@*Conclusions@#In patients with heart failure, the inner diameter of the femoral vein/femoral artery ratio is positively correlated with CVP and mPAWP. The ratio of inner diameter of the femoral vein/femoral artery can be used to assess the volumetric load of patients with heart failure and to guide the clinical treatment of heart failure patients.