Effects of Fdft 1 gene silencing and VD3 intervention on lung injury in hypoxia-stressed rats

Pu Xiaoyan,Lin Xue,Qi Yinglian,Li Yinglian,Li Tiantian,Liu Yang,Wei Dengbang 한국유전학회 2022 Genes & Genomics Vol.44 No.10

Background: Hypoxia can induce lung injury such as pulmonary arterial hypertension and pulmonary edema. And in the rat model of hypoxia-induced lung injury, the expression of Farnesyl diphosphate farnesyl transferase 1 (Fdft 1) was highly expressed and the steroid biosynthesis pathway was activated. However, the role of Fdft 1 and steroid biosynthesis pathway in hypoxia-induced lung injury remains unclear. Objective: The study aimed to further investigate the relationship between Fdft1 and steroid biosynthesis pathway with hypoxia-induced lung injury. Methods: A rat model of lung injury was constructed by hypobaric chamber with hypoxic stress, the adenovirus interference vector was used to silence the expression of Fdft 1, and the exogenous steroid biosynthesis metabolite Vitamin D3 (VD3) was used to treat acute hypoxia-induced lung injury in rats. Results: Sh-Fdft 1 and exogenous VD3 significantly inhibited the expression of Fdft 1 and the activation of the steroid pathway in hypoxia-induced lung injury rats, which showed a synergistic effect on the steroid activation pathway. In addition, sh-Fdft 1 promoted the increase of pulmonary artery pressure and lung water content, the decrease of oxygen partial pressure and oxygen saturation, and leaded to the increase of lung cell apoptosis and the aggravation of mitochondrial damage in hypoxia-stressed rats. And VD3 could significantly improve the lung injury induced by hypoxia and sh-Fdft 1 in rats. Conclusions: Fdft 1 gene silencing can promote hypoxic-induced lung injury, and exogenous supplement of VD3 has an antagonistic effect on lung injury induced by Fdft 1 gene silencing and hypoxic in rats, suggesting that VD3 has a preventive and protective effect on the occurrence and development of hypoxia-induced lung injury.

Acid Exposure Time > 6% Might Not Improve the Therapeutic Outcome in Chinese Gastroesophageal Reflux Disease Patients

( Yuqing Lin ),( Yuwen Li ),( Mengya Liang ),( Niandi Tan ),( Mengyu Zhang ),( Songfeng Chen ),( Yinglian Xiao ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.1

Background/Aims There is less acid burden in Chinese gastroesophageal reflux disease (GERD) patients. However, the Lyon consensus proposed a higher threshold of acid exposure time (AET > 6%) for GERD. The aims are to apply the updated criteria in Chinese GERD patients and clarify its influence on clinical outcome. Methods Patients who were referred for both esophageal high-resolution manometry and 24-hour esophageal pH monitoring due to reflux symptoms were retrospectively screened. Those patients with AET > 4% was included and grouped into either AET 4-6% or AET > 6%. Their manometric profile, reflux profile, and response to proton pump inhibitors (PPIs) were evaluated. Adjunctive evidence proposed in the Lyon consensus was added in patients with AET 4-6% for therapeutic gain. Another group of patients (n = 144) with AET < 4% were included as non-GERD patients. Results In total, 151 patients (102 males) were included with 113 patients AET > 6% (74.9%). GERD patients with AET > 4% were with more male, older patients, and higher body mass index compared with non-GERD patients. Meanwhile, GERD patients were less competent in esophagogastric junction pressure. However, the manometric and reflux profile were similar between patients with AET > 6% and 4-6%. The response rate of PPI therapy was 64.6% and 63.2%, respectively, in groups of AET > 6% and 4-6% (P > 0.05). When adjunctive evidence was added in patients with AET 4-6%, no therapeutic gain was obtained. Conclusions The efficacy of PPI therapy was similar in patients with AET > 6% and 4-6%. The increase of the AET threshold did not influence the clinical outcome of Chinese GERD patients. (J Neurogastroenterol Motil 2021;27:55-62)

Esophagogastric Junction Contractility Integral Reflect the Anti-reflux Barrier Dysfunction in Patients with Gastroesophageal Reflux Disease

( Chenxi Xie ),( Jinhui Wang ),( Yuwen Li ),( Niandi Tan ),( Yi Cui ),( Minhu Chen ),( Yinglian Xiao ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.1

Background/Aims Anti-reflux barrier dysfunction is one of the primary mechanisms in gastroesophageal reflux disease (GERD) pathogenesis. The esophagogastric junction contractile integral (EGJ-CI) is a new metric adopted to evaluate the EGJ contractility, which implies the antireflux barrier function. The aim of the current study was to validate this new metric in patients with GERD and its correlation with the esophageal acid exposure, as well as the efficacy of proton pump inhibitor treatment. Methods Ninety-eight patients with GERD and 21 healthy controls were included in the study. Upper endoscopy, high-resolution manometry (HRM) and 24-hour multichannel intraluminal impedance-pH monitoring were performed in all patients. Three respiration cycles were chosen at the initial HRM resting frame and the value computed with distal contractile integral tool was then divided by the duration of the cycles to yield EGJ-CI. All the patients were treated with esomeprazole 20 mg twice-daily for 8 weeks. Results EGJ-CI was lower in the patients with GERD than that of the controls (P < 0.05). For patients with GERD, EGJ-CI was lower in those with hiatal hernia (P < 0.05). The new metric correlated with esophageal acid exposure in the supine position (P < 0.05), and it also negatively correlated to the total reflux episodes (P < 0.05). There was no significant difference on EGJ-CI between patients with and without response to the esomeprazole treatment (P = 0.627). Conclusions EGJ-CI reflected the dysfunction of the anti-reflux barrier in patients with GERD, but it had little impact on the esomeprazole response. (J Neurogastroenterol Motil 2017;23:27-33)

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment

( Chenxi Xie ),( Daniel Sifrim ),( Yuwen Li ),( Minhu Chen ),( Yinglian Xiao ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

Background/Aims Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. Methods Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. Results The intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 mm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = -0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = -0.230, P < 0.05). “Baseline impedance > 1764 Ω” was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P < 0.01). Conclusions The DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment. (J Neurogastroenterol Motil 2018;24:43-50)