TRPA1 protects mice from pathogenic Citrobacter rodentium infection via maintaining the colonic epithelial barrier function.

Transient receptor potential ankyrin 1 (TRPA1) is expressed in gastrointestinal tract and plays important roles in intestinal motility and visceral hypersensitivity. However, the potential role of TRPA1 in host defense, particularly against intestinal pathogens, is unknown. Here, we show that Trpa1 knockout mice exhibited increased susceptibility to Citrobacter rodentium infection, associated with the increased severity of diarrhea and intestinal permeability associated with the disrupted tight junctions (TJs) in colonic epithelia. We further demonstrated the expression of TRPA1 in murine colonic epithelial cells (CECs) and human epithelial Caco-2 cells both at protein level and transcription level. Using calcium imaging, TRPA1 agonists allyl isothiocyanates (AITC) and hydrogen peroxide were observed to induce a transient Ca2+ response in Caco-2 cells, respectively. Moreover, TRPA1 knockdown in Caco-2 cells resulted in the decreased expression of TJ proteins, ZO-1 and Occludin, and in the increased paracellular permeabilities and the reduced TEER values of Caco-2 monolayers in vitro. Furthermore, inhibition of TRPA1 by HC-030031 in the confluent Caco-2 cells caused the altered distribution and expression of TJ proteins, ZO-1, Occludin, and Claudin-3, and exacerbated the bacterial endotoxin lipopolysaccharide (LPS)-induced damage to these TJ proteins and actin cytoskeleton. By contrast, AITC pretreatment restored the distribution and expression of these TJ proteins in the confluent Caco-2 cells upon LPS challenge. Our results identify an unrecognized protective role of TRPA1 in host defense against an enteric bacterial pathogen by maintaining colonic epithelium barrier function, at least in part, via preserving the distribution and expression of TJ proteins in CECs.

Urine Output Is Associated With In-hospital Mortality in Intensive Care Patients With Septic Shock: A Propensity Score Matching Analysis.

Background: The relationship between urine output (UO) and in-hospital mortality in intensive care patients with septic shock is currently inconclusive. Methods: The baseline data, UO, and in-hospital prognosis of intensive care patients with septic shock were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. By drawing receiver operating characteristic (ROC) curves and comparing the areas under the ROC curves (AUC) to determine the predictive value of UO for in-hospital mortality, and by drawing the Kaplan-Meier curves to compare the difference in in-hospital mortality between different groups of UO. Results: Before and after the propensity score matching (PSM) analysis, UO was always a risk factor for in-hospital mortality in patients with septic shock. The AUC of UO was comparable to the Sequential Organ Failure Assessment (SOFA) scoring system, while the AUC of combining UO and SOFA was greater than that of SOFA. The median survival time of the high-UO group (UO > 0.39 ml/kg/h, before PSM; UO > 0.38 ml/kg/h, after PSM) was longer than that of the low-UO group. Compared with the high-UO group, the hazard ratios (HR) of the low-UO group were 2.6857 (before PSM) and 1.7879 (after PSM). Conclusions: UO is an independent risk factor for septic shock. Low levels of UO significantly increase the in-hospital mortality of intensive care patients with septic shock. The predictive value of UO is comparable to the SOFA scoring system, and the combined predictive value of the two surpasses SOFA alone.

Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines.

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN. Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples. Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001). Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200-250 W is effective and safe in normal-sized canines.

[Biomechanical comparison study of two ultra-strong sutures in repair of Achilles tendon via panda rope bridge technique].

OBJECTIVE: To compare the biomechanical properties of two ultra-strong sutures and suturing methods in panda rope bridge technique (PRBT) application, and provide guidance for clinical selection of suture threads and suture methods. METHODS: Forty Achilles tendons from bulls were randomly divided into 4 groups ( n=10) and transected at the 4 cm proximal to the tendon insertion. Groups A and B used Ethibond sutures (USP 5), the proximal end was fixed at the myotendious junction with Krackow sutures and the distal end was fixed through a calcaneus canal. Groups A and B had 4 and 8 threads through the stump plane, respectively. Groups C and D used Ultrabraid sutures (USP 2), the proximal end was fixed at the myotendious junction with Krackow sutures and the distal end was fixed in the calcaneus with two anchors. Groups C and D had 4 and 8 threads through the stump plane, respectively. The dynamic tensile forces of 20-100, 20-200, 20-300, and 20-400 N were tested respectively by using a dynamic tensile testing machine at 0.5 Hz for 250 cycles. After each stage of testing, the gap between stumps was measured with a caliper and the type of suture failure was recorded. RESULTS: After dynamic tensile forces of 20-100 N and 20-200 N, the gaps of the four groups arranged from small to large were groups D, B, C, and A. The differences between groups A and B and groups C and D were significant ( P<0.05). But after dynamic tensile forces of 20-300 N and 20-400 N, the gaps were more than 5 mm in all groups. The suture retention rates of the four groups after dynamic tensile forces of 20-100 N and 20-200 N were all 100%. The suture retention rates of groups A, B, C, and D were 0, 80%, 60%, and 100%, respectively after dynamic tensile forces of 20-300 N. The differences of suture retention rates between group A and groups B and D were significant ( P<0.05). There was no significant difference between groups B, C, and D ( P>0.05). After dynamic tensile forces of 20-400 N, the suture retention rates of groups A, B, C, and D were 0, 50%, 0, and 70%, respectively. There were significant differences between groups A and B and groups C and D ( P<0.05). CONCLUSION: Repairing Achilles tendon rupture via PRBT with 8 ultra-strong sutures through the stump plane can meet the mechanical requirements for walking by using ankle boots and heel pads in the early accelerated rehabilitation after operation.

Annealing effects on microstructure and laser-induced damage threshold of quasi-rugate filters.

Ta2O5/SiO2 quasi-rugate filters with high damage thresholds were deposited by ion-beam sputtering and then annealed at temperature of 200-800°C. The relations between microstructure, optical properties, chemical composition, weak absorption, and laser-induced damage threshold (LIDT) were studied. It was found that the transmittance spectra shifted to short wavelength as the annealing temperature increased. Three evolution courses of the films in the annealing process were analyzed by Atomic Force microscopy (AFM), Zygo interferometer measurement and Focused Ion Beam microscope (FIB). The decreased weak absorption during annealing process was found with significant effect on the LIDT. As the annealing temperature increased to 600°C, the weak absorption of films decreased from 39.99 to 7.2 ppm and the 50%-LIDTs increased from 59.32 to 158.87J/cm2. Distinct damage micrographs of the films annealed at different temperature were obtained. A combination of substoichiometric defect and structural defect dominant description was used to illustrate the aggravation of laser-induced damage.

Complementary prognostic values of ST segment deviation and Thrombolysis In Myocardial Infarction (TIMI) risk score in non-ST elevation acute coronary syndromes: Insights from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study.

BACKGROUND: Although the Thrombolysis In Myocardial Infarction (TIMI) score incorporates ST deviation, it does not account for characteristics of the ST deviations. In the present study, it was hypothesized that the magnitude and characteristics of ST deviation may add to the prognostic values of the TIMI risk score in acute coronary syndrome (ACS) patients, particularly in lower-risk patients with a TIMI risk score of less than 5. OBJECTIVE: To evaluate the prognostic value of combining the TIMI risk score and characteristics of ST deviation in patients with non-ST elevation ACS and a TIMI risk score of less than 5. METHODS: The death/myocardial infarction (MI) rates of 1296 patients enrolled in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) angiographic substudy were examined. RESULTS: Patients without a TIMI risk score of 5 or greater, and without an ST deviation of 1 mm or greater had the lowest six-month rate of death/ MI (5%). In patients with a TIMI risk score of less than 5, the six-month death/MI rate was increased in those with ST depression of 2 mm or greater compared with patients with a similar TIMI risk score and without ST deviation of 1 mm or greater (24% versus 5%, P<0.001). The presence of ST deviation of 2 mm or greater identified an additional 15% of patients with an increased six-month death/MI rate in patients with a TIMI risk score of less than 5. CONCLUSION: ST segment deviation of 2 mm or greater confers additional prognostic information in non-ST elevation ACS patients with a TIMI risk score of less than 5. Patients with a TIMI risk score of less than 5 and ST deviation of 2 mm or less had the lowest risk of six-month death/MI.