薄荷醇通过调节食管上皮细胞 TRPV1 缓解酸反流炎症。
- 作者列表："Zhang Z","Wu X","Zhang L","Mao A","Ma X","He D
:Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays an important role in pain and inflammatory responses. Previous studies have shown that the expression of TRPV1 increases in the sensory neurons of the esophagus during the development of gastroesophageal reflux disease and esophagitis, but the response of TRPV1 in esophageal epithelial cells (EECs), which directly confront the refluxed acid, is still unknown. Here, we found that acid reflux triggered esophageal damage, which was accompanied by increased expression of TRPV1 in EECs and TRPV1 channel activity in these cells. Furthermore, menthol inhibited the Ca2+ influx induced by acid stimulation in EECs. After menthol treatment, the expression of TRPV1 in EECs was significantly reduced, and their hyperplasia was significantly reduced; finally, the inflammation pathway elicited in EECs was diminished in mice with acid reflux. These results suggest that menthol improves the clinical symptoms caused by gastroesophageal acid reflux by interfering with TRPV1 in EECs.
: 瞬时受体电位阳离子通道亚家族 V 成员 1 (TRPV1) 在疼痛和炎症反应中起重要作用。既往研究表明，在胃食管反流病和食管炎的发展过程中，TRPV1 在食管感觉神经元中的表达增加，但 TRPV1 在食管上皮细胞 (EECs) 中的反应, 它直接面对回流酸，仍然是未知的。在这里，我们发现酸反流触发了食管损伤，伴随着 EECs 中 TRPV1 的表达增加和这些细胞中 TRPV1 通道活性的增加。此外，薄荷醇抑制了酸刺激诱导的 EECs 中 Ca2 + 内流。薄荷醇处理后，EECs 中 TRPV1 的表达显著减少，其增生显著减少; 最后，酸反流小鼠 EECs 中引发的炎症通路减少。这些结果提示薄荷醇通过干扰 EECs 中 TRPV1 改善胃食管酸反流引起的临床症状。
METHODS:PURPOSE:The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods:A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. RESULTS:With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. CONCLUSION:No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.
METHODS::The radial force of esophageal stents may not completely change during extraction and therefore, the procedure of stent removal may cause tissue damage. The present study reports the manufacture of 2 novel detachable stents, which were designed to reduce tissue damage through their capacity to be taken or fall apart prior to removal and evaluated the supporting properties of these stents and the extent of local mucosal injury during their removal. The stents were manufactured by braiding, heat-setting, coating and connecting. The properties of the stents were evaluated by determining the following parameters: Expansion point, softening point, stent flexibility, radial compression ratio and radial force. A total of 18 rabbits with induced esophageal stricture were randomly assigned to 3 groups as follows: Detachable stent (DS) group, biodegradable stent (BS) group and control group. The stricture rate, complications, survival, degradation and stent removal were observed over 8 weeks. The stents of the DS and BS groups provided a similar supporting effect. The stricture rate, incidence of complications and survival were also similar between the 2 groups, while significant differences were noted between the DS and control groups and between the BS and control groups. In the BS group, the stents were degraded and moved to the stomach within 7 weeks (2 in 6 weeks and 3 in 7 weeks). The debris was extracted using biopsy forceps. In the DS group, all stents were easy to remove and 2 cases exhibited minor hemorrhage. In conclusion, the 2 types of novel detachable stent provided an equally efficient supporting effect in vitro and in vivo and may reduce the incidence of secondary injury during stent removal.
METHODS:BACKGROUND:Immune imbalance and inflammation have been suggested as key factors of Barrett's esophagus (BE) pathway towards adenocarcinoma. The neutrophil-lymphocyte ratio (NLR) indirectly reflects the relation between innate and adaptive immune systems and has been studied in premalignant conditions as a biomarker for cancer diagnosis. Our aim was to investigate if increasing values of NLR correlated with advancing stages of BE progression to dysplasia and neoplasia. METHODS:We retrospectively analyzed data of patients with biopsies reporting BE between 2013 and 2017 and with a complete blood count within 6 months from the endoscopy, as well as patients with esophageal adenocarcinoma (EAC). NLR was calculated as neutrophil count/lymphocyte count. Cases (n = 113) were classified as non-dysplastic BE (NDBE, n = 72), dysplastic BE (DBE, n = 11) and EAC (n = 30). RESULTS:NLR progressively increased across groups (NDBE, 1.92 ± 0.7; DBE, 2.92 ± 1.1; EAC 4.54 ± 2.9), with a significant correlation between its increasing value and the presence of dysplasia or neoplasia (r = 0.53, p 2.27 was able to diagnose EAC with 80% sensitivity and 71% specificity (area under the curve = 0.8). CONCLUSION:NLR correlates with advancing stages of BE progression, a finding that reinforces the role of immune imbalance in EAC carcinogenesis and suggests a possible use of this marker for risk stratification on surveillance strategies.