New endoscopic closure technique, "internal traction-assisted suspended closure," for GI defect closure: a pilot study (with video).

BACKGROUND AND AIMS: After endoscopic full-thickness resection (EFTR), reliable closure of the perforation is critical. However, it is technically difficult to close some defects by using metal clips alone or by purse-string suturing, which may lead to unreliable closure. Inspired by the process of pulling up the 2 ends of the incision in the surgical suture, we developed a new endoscopic closure technique, the "internal traction-assisted suspended closure" technique. This pilot study was performed as an initial evaluation of the feasibility and safety of this new endoscopic closure technique. METHODS: Data from patients in whom this suspended closure technique was used to close full-thickness defects after EFTR were retrospectively reviewed. The primary outcome was successful closure rate. Secondary outcomes were closure time, length of postprocedural hospital stay, and incidence of postprocedural adverse events. Defect size and tumor characteristics were also analyzed. RESULTS: Eight patients who underwent the suspended closure technique after EFTR were included. All patients were successfully treated with the suspended closure technique, and no patient developed serious adverse events. The median length of the defect was 3.25 cm (range, 2.5-9.0) and the median width was 2.8 cm (range, 1.8-6.0). The median closing time was 13 minutes (range, 6-24). CONCLUSIONS: The internal traction-assisted suspended closure technique is a simple, reliable, and easy-to-use technique for large full-thickness defects after endoscopic resection.

A novel risk score model of esophageal stricture for patients undergoing endoscopic submucosal dissection.

BACKGROUND AND PURPOSE: Endoscopic submucosal dissection (ESD) is a promising technique for superficial esophageal lesions. However, stricture is a frequent adverse complication. This study was performed to develop a precise and convenient score prediction model for esophageal strictures after ESD, and compare its efficacy with a previously published predictive model. METHODS: This study enrolled clinical data of patients who underwent esophageal ESD for superficial esophageal lesions. Possible risk factors for esophageal stricture were identified by univariate and multivariate logistic regression analysis. Then we developed a prediction model according to the Framingham system for the first time and presented a convenient table containing the risk probability for each patient. In addition, we validated our score model and the previously published model in our center. RESULTS: A total of 838 patients were enrolled in this study and 6 variables, including age, surgery time, location of the lesion, circumference of the lesion, longitudinal resection length, and depth of infiltration were comprised in the score model. The total score ranged from 0 to 16 points and the risk probability was presented in one concise table for each patient. Areas under receiver-operator characteristic curves for the prediction model were 0.715 in derivation group and 0.804 in validation group. CONCLUSION: We designed and validated a prediction score model for esophageal stricture after ESD, which can be applied conveniently to stratify the stricture risk after esophageal ESD and may facilitate appropriate clinical decision-making for these patients.

Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer.

Immunotherapy is a promising treatment for advanced colorectal cancers (CRCs). However, immunotherapy resistance remains a common problem. Immunogenic cell death (ICD), a form of regulated cell death, induces adaptive immunity, thereby enhancing anti-tumor immunity. Research increasingly suggests that inducing ICD is a promising avenue for cancer immunotherapy and identifying ICD-related biomarkers for CRCs would create a new direction for targeted therapies. Thus, this study used bioinformatics to address these questions and create a prognostic signature, aiming to improve individualized CRC treatment. We identified two ICD -related molecular subtypes of CRCs. The high subtype showed pronounced immune cell infiltration, high immune activity, and high expression of human leukocyte antigen and immune checkpoints genes. Subsequently, we constructed and validated a prognostic signature comprising six genes (CD1A, TSLP, CD36, TIMP1, MC1R, and NRG1) using random survival forest analyses. Further analysis using this prediction model indicated that patients with CRCs in the low-risk group exhibited favorable clinical outcomes and better immunotherapy responses than those in the high-risk group. Our findings provide novel insights into determining the prognosis and design of personalized immunotherapeutic strategies for patients with CRCs.

Efficacy of two endoscopic rubber band ligation methods for symptomatic hemorrhoids: a randomized controlled trial.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is considered an effective nonsurgical treatment for symptomatic grade I to III hemorrhoids; however, it is unclear whether ligation of hemorrhoids or simultaneous ligation of hemorrhoids and proximal normal mucosa (combined ligation) is safer and more effective. This controlled, open-label, and prospective study aimed to evaluate the efficacy and safety of both methods for symptomatic grade I to III hemorrhoids. METHODS: Seventy patients with symptomatic grade I to III hemorrhoids were randomly assigned to the hemorrhoid and combined ligation groups (35 in each group). Patients were followed up at 3, 6, and 12 months to assess symptom improvement, complications, and recurrence. The primary outcome was overall therapeutic success rate (complete resolution and partial resolution rates). The secondary outcomes included recurrence rate and efficacy for each symptom. Complications and patient satisfaction were also assessed. RESULTS: Sixty-two patients (31 in each group) completed the 12-month follow-up; 42 (67.8%) experienced complete resolution, 17 (27.4%) experienced partial resolution, and 3 (4.8%) experienced no change in overall efficacy. The rates of complete resolution, partial resolution, and no change in the hemorrhoid ligation and combined ligation groups were 71.0 and 64.5%, 22.6 and 32.3%, and 6.5 and 3.2%, respectively. No significant differences in overall efficacy, recurrence rate, or efficacy for each symptom (including bleeding, prolapse, pain, anal swelling, itching, soiling, and constipation) were observed between groups. No life-threatening events requiring surgical intervention occurred. The incidence of postoperative pain was higher in the combined ligation group (74.2% vs. 45.2%, P = 0.02). No significant differences between groups in terms of incidences of other complications or patient satisfaction were observed. CONCLUSION: Both methods achieved satisfactory therapeutic effects. No significant differences in efficacy and safety of the two ligation methods were observed; however, combined ligation resulted in a higher incidence of postprocedural pain.

Comparison of statins with steroids and botulinum toxin A in the prevention of benign strictures after esophageal endoscopic submucosal dissection: a retrospective cohort study.

BACKGROUND: Preventing benign strictures following esophageal endoscopic submucosal dissection (ESD) remains difficult, and finding a safe, effective, and simple management method is vital. We previously reported that rosuvastatin significantly reduced the incidence and severity of strictures in a rabbit model of esophageal stricture. Accordingly, in this study, we compared the effects of statins, steroids, and botulinum toxin A (BTX-A) on stricture prevention after ESD involving more than three-fourths of the luminal circumference. METHODS: Of the 1019 ESD cases treated between January 2015 and December 2020, 246 met the inclusion criteria, with 21 cases excluded due to loss to follow-up, tumor recurrence, death, or need for additional surgery, radiotherapy, and/or chemotherapy. Of the 225 included cases, 145 received no intervention, while the remaining 80 were treated: 16 with oral steroids, 20 with topical triamcinolone acetonide (TA) injection, 21 with topical BTX-A injection, and 23 with statins. RESULTS: The occurrence stricture rate in the statins group (17.4%, 4/23) was significantly lower than in the non-intervention (75.2%, 109/145, P = 0.000), oral steroids (56.3%, 9/16, P = 0.011) and TA injection (50%, 10/20, P = 0.023) groups, but comparable to in the BTX-A injection (38.1%, 8/21, P = 0.124) group. The dysphagia score was lower in the statin than non-intervention group (P = 0.000). Although there was no significant difference in the number of required dilations between groups, the maximum number of dilations in the statins group was only six. CONCLUSIONS: Statins may be a potential treatment to prevent esophageal strictures after extensive ESD; however, clinical trials should be conducted to validate this.

Noninvasive Transcutaneous Auricular Vagal Nerve Stimulation Improves Gastric Slow Waves Impaired by Cold Stress in Healthy Subjects.

BACKGROUND/AIMS: Stress is known to inhibit gastric motility. The aim of this study was to investigate the effects and autonomic mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) on cold stress (CS)-induced impairment in gastric motility that are relevant to the brain-gut interactions in healthy volunteers. MATERIALS AND METHODS: Healthy volunteers (eight women; age 28.2 ± 1.8 years) were studied in four randomized sessions (control, CS, CS + taVNS, and CS + sham-electrical stimulation [sham-ES]). Each session was composed of 30 minutes in the fasting state and 30 minutes after a standard test meal. CS was induced during minutes 10 to 30 after the meal, whereas taVNS or sham-ES was performed during minutes 0 to 30 after the meal. The electrogastrogram and electrocardiogram were recorded for assessing gastric slow waves and autonomic functions, respectively. RESULTS: First, CS decreased the percentage of normal gastric slow waves (59.7% ± 9.8% vs 85.4% ± 4.5%, p < 0.001 vs control); this impairment was dramatically improved by taVNS (75.5% ± 6.3% vs 58.4% ± 12.5%, p < 0.001 vs sham-ES). Second, CS increased the symptom score (22.0 ± 12.1 vs 39.3 ± 11.5, p = 0.001 vs control); taVNS, but not sham-ES, reduced the symptom score (26.0 ± 12.2 vs 38.3 ± 21.6, p = 0.026 vs sham-ES). Third, CS decreased vagal activity assessed from the spectral analysis of heart rate variability (0.21 ± 0.10 vs 0.26 ± 0.11, p < 0.05 vs control) and increased the sympathovagal ratio (4.89 ± 1.94 vs 3.74 ± 1.32, p = 0.048 vs control); taVNS normalized CS-induced suppression in vagal activity (0.27 ± 0.13 vs 0.22 ± 0.10, p = 0.049 vs sham-ES; p > 0.05 vs control) and CS-induced increase in the sympathovagal ratio (3.28 ± 1.61 vs 4.28 ± 2.10, p = 0.042 vs sham-ES; p > 0.05 vs control). CONCLUSION: The noninvasive taVNS improves the CS-induced impairment in gastric pace-making activity, possibly by reversing the detrimental effect of CS on autonomic functions. taVNS may have a therapeutic potential for stress-induced gastric dysmotility.

Establishment of anammox coupled with sulfide-depending autotrophic denitrification process and its efficient pollutants removal performance.

Nitrogen and sulfur pollutants coexist in many industrial wastewaters, which may cause serious water pollution issues. In this study, Anammox coupled with sulfide-depending autotrophic denitrification process (coupling process) was established by adding sulfide to an Anammox system in a membrane bioreactor. Variations in nitrogen and sulfur removal performance, extracellular polymeric substances (EPS), key enzyme activities, and microbial components were analyzed. The sulfide in 25.0 mg L-1 successfully induced denitrification, and then helped establish the coupling process. This process achieved 96.1% TN removal and complete sulfide removal when the sulfide was increased to 100.0 mg L-1. The protein and polysaccharide in EPS gradually increased to 2.0 and 4.9 mg g-1 SS, respectively. The hydroxylamine oxidoreductase activity, Heme-c content, nitrite reductase activity, and nitrate reductase activity slightly decreased to 19.1 EU g-1 SS, 0.001 mmol g-1 SS, 0.002 µg min-1 mg-1 protein, and 0.005 µg min-1 mg-1 protein, respectively, indicating the slight suppression of sulfide in high concentration on the coupling process. However, after acclimatization, the Anammox and denitrifying bacteria interacted and cooperatively contributed to the simultaneous nitrogen and sulfur removal, with relative abundances of Thiobacillus-denitrifying bacteria and Candidatus Kuenenia-Anammox bacteria of 31.7% and 9.0%, respectively. The establishing strategy was proposed and then verified in another Anammox system, in which the coupling process was also established, with TN removal increasing from 73.4% to 82.5%.

Protective effect of rosuvastatin against the formation of benign esophageal stricture.

BACKGROUND: Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model. METHODS: Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin-eosin and Masson staining. The expressions of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry. RESULTS: The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-ß1, CTGF, and α-SMA significantly reduced in the rosuvastatin group. CONCLUSIONS: The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-ß1.

A Comparative Study of the Properties of Recycled Concrete Prepared with Nano-SiO2 and CO2 Cured Recycled Coarse Aggregates Subjected to Aggressive Ions Environment.

This research focused on the modification effects on recycled concrete (RC) prepared with nano-SiO2 and CO2 cured recycled coarse aggregates (RCA) subjected to an aggressive ions environment. For this purpose, RCA was first simply crushed and modified by nano-SiO2 and CO2, respectively, and the compressive strength, ions permeability as well as the macro properties and features of the interface transition zone (ITZ) of RC were investigated after soaking in 3.5% NaCl solution and 5% Na2SO4 solution for 30 days, respectively. The results show that nano-SiO2 modified RC displays higher compressive strength and ions penetration resistance than that treated by carbonation. Besides, we find that ions attack has a significant influence on the microcracks width and micro-hardness of the ITZ between old aggregate and old mortar. The surface topography, elemental distribution and micro-hardness demonstrate that nano-SiO2 curing can significantly decrease the microcracks width as well as Cl- and SO42- penetration in ITZ, thus increasing the micro-hardness, compared with CO2 treatment.

MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle Cells via the Targeting of the miR-449a/DLL1 Axis in Diabetic Gastroparesis.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular Ca2+ changes in human gastric smooth muscle cells (HGSMCs) under high glucose (HG) conditions, using short hairpin RNA technology, RNA immunoprecipitation, and dual-luciferase reporter assays. We show that MALAT1 expression was upregulated in the gastric tissues of DGP model mice, the adjacent healthy tissues collected from diabetic gastric cancer patients with DGP symptoms, and in HGSMCs cultured under HG conditions. Functionally, MALAT1 knockdown in vitro impacted the viability, proliferation, migration and promoted the phenotypic switch of HGSMCs under HG conditions. Additionally, we show that MALAT1 sponged miR-449a, regulating Delta-like ligand 1 (DLL1) expression in HGSMCs; any disturbance of the MALAT1/miR-449a/DLL1 pathway affects the proliferation, migration, phenotypic switch, and carbachol-induced Ca2+ transient signals in HGSMCs under HG conditions. Collectively, our data highlight a novel regulatory signaling pathway, the MALAT1/miR-449a/DLL1 axis, in the context of DGP.

Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia by enhancing vagal efferent activity.

This study was designed to investigate whether transcutaneous auricular vagal nerve stimulation (taVNS) would be able to improve major pathophysiologies of functional dyspepsia (FD) in patients with FD. Thirty-six patients with FD (21 F) were studied in two sessions (taVNS and sham-ES). Physiological measurements, including gastric slow waves, gastric accommodation, and autonomic functions, were assessed by the electrogastrogram (EGG), a nutrient drink test and the spectral analysis of heart rate variability derived from the electrocardiogram (ECG), respectively. Thirty-six patients with FD (25 F) were randomized to receive 2-wk taVNS or sham-ES. The dyspeptic symptom scales, anxiety and depression scores, and the same physiological measurements were assessed at the beginning and the end of the 2-wk treatment. In comparison with sham-ES, acute taVNS improved gastric accommodation (P = 0.008), increased the percentage of normal gastric slow waves (%NSW, fasting: P = 0.010; fed: P = 0.007) and vagal activity (fasting: P = 0.056; fed: P = 0.026). In comparison with baseline, 2-wk taVNS but not sham-ES reduced symptoms of dyspepsia (P = 0.010), decreased the scores of anxiety (P = 0.002) and depression (P < 0.001), and improved gastric accommodation (P < 0.001) and the %NSW (fasting: P < 0.05; fed: P < 0.05) by enhancing vagal efferent activity (fasting: P = 0.015; fed: P = 0.048). Compared with the HC, the patients showed increased anxiety (P < 0.001) and depression (P < 0.001), and decreased gastric accommodation (P < 0.001) and %NSW (P < 0.001) as well as decreased vagal activity (fasting: P = 0.047). The noninvasive taVNS has a therapeutic potential for treating nonsevere FD by improving gastric accommodation and gastric pace-making activity via enhancing vagal activity.NEW & NOTEWORTHY Treatment of functional dyspepsia is difficult due to various pathophysiological factors. The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions (accommodation and slow waves), possibly mediated via the enhancement of vagal efferent activity. This noninvasive and easy-to-implement neuromodulation method will be well received by patients and healthcare providers.

Transcutaneous Electrical Acustimulation Improves Gastrointestinal Disturbances Induced by Transcatheter Arterial Chemoembolization in Patients With Liver Cancers.

BACKGROUND: Gastrointestinal (GI) disturbances occur in patients who receive chemotherapy via transcatheter arterial chemoembolization (TACE) and could last for an extended period of time in some cases. Antiemetic drugs have a potential risk of developing hepatic failure and are ineffective for delayed nausea and emesis. Transcutaneous electrical acustimulation (TEA) has recently been reported to exert antiemetic and prokinetic effects, but it is unknown whether it has an ameliorating effect on TACE-induced GI disturbances. AIM: This study was designed to evaluate effects and mechanisms of noninvasive TEA on GI symptoms in patients treated with TACE. MATERIALS AND METHODS: Seventy-four patients with liver cancers (eighteen female; age 63.4 ± 1.1 years) scheduled for TACE were randomized to TEA (n = 37) or sham-TEA (n = 37). TEA was performed via acupoints, ST36 and PC6 using parameters previously optimized for GI motility (1 h, bid) from the postoperative day 0 (POD0) to POD2. Sham-TEA was performed using the same parameters via non-acupoints. Symptom questionnaires were completed daily. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded in the fasting state for 30 mins to assess gastric slow waves and autonomic functions, respectively, before and after the 3-day treatment. RESULTS: 1) In the acute phase (<24 h), TEA showed no effects on any of GI symptoms, compared with sham-TEA. 2) In the delayed phase (>24 h), TEA, compared with sham-TEA, decreased the percentage of patients who experienced nausea on POD3 (0% vs. 13.5%, p = 0.021), the nausea score on POD3 (p = 0.022), the anorexia score on POD2 (p = 0.040) and POD3 (p = 0.004), and the bloating score (POD1-3: p < 0.01). 3) In comparison with sham-TEA, TEA increased the number of spontaneous bowel movements (p = 0.001) and the Bristol score of the first stool (p = 0.014) and decreased the number of patients with the use of laxatives (p = 0.022). 4) Physiologically, the 3-day TEA but not sham-TEA increased the percentage of normal gastric slow waves (p < 0.001) and vagal activity (p = 0.006). The vagal activity was negatively correlated with the anorexia score (r = -0.267, p = 0.026). It was found that the sympathovagal ratio and tumor size>5 cm were independent risk factors predicting the occurrence of nausea in patients after TACE. CONCLUSION: TEA improves major TACE-induced GI disturbances in the delayed phase, including nausea, bloating, impaired gastric pace-making activity, and constipation in patients with liver cancers via the autonomic pathway.

Total Panax notoginseng saponin inhibits vascular smooth muscle cell proliferation and migration and intimal hyperplasia by regulating WTAP/p16 signals via m6A modulation.

Intimal hyperplasia, the key event of arterial restenosis, is a result of vascular smooth muscle cell (VSMC) proliferation and migration. Previous studies have demonstrated that total Panax notoginseng saponin (TPNS) represses intimal hyperplasia and inhibits the proliferation of VSMCs following balloon injury. However, the underlying roles of TPNS in intimal hyperplasia remain unclear. In this study, we first found that TPNS inhibited the intimal hyperplasia and reversed the reduced m6A quantity in balloon catheter-injured rat carotid artery. Then, we measured the expression profiles of m6A "writers" (i.e., methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), and WT1 associated protein (WTAP)) and "erasers" (i.e., FTO alpha-ketoglutarate dependent dioxygenase (FTO) and alkB homolog 5, RNA demethylase (ALKBH5)) in vivo and found that TPNS up-regulated the reduced the WTAP expression in balloon catheter-injured rat carotid artery. Furthermore, we illustrated that TPNS inhibited the viability, proliferation, and migration potential of VSMCs via promotion of WTAP expression and suppression of WTAP restored the TPNS-induced inhibition of cell viability, proliferation and migration potential of VSMCs. In addition, we found that p16 was up-regulated in VSMCs treated with TPNS and repression of p16 restored the TPNS-induced inhibition of cell viability, proliferation and migration potential of VSMCs. Finally, we elucidated that, mechanistically, WTAP exerted its role by regulating p16 via m6A modification. Collectively, our results reveal the WTAP-p16 signaling axis and highlight the critical roles of m6A modification in intimal hyperplasia. Thus, this study provided a potential biomarker for the assessment of intimal hyperplasia risk following angioplasty as well as a novel therapeutic target for this disease.

Isolated gastric varices secondary to abdominal tuberculosis mimicking lymphoma: a case report.

BACKGROUND: Abdominal tuberculosis (TB) rarely presents with abdominal masses and rarely causes isolated gastric varices. CASE PRESENTATION: We report a case of isolated gastric varices secondary to abdominal TB mimicking lymphoma. A 42-year-old woman without any history of liver disease presented with melena and mild abdominal pain. Upon admission to the hospital, laboratory investigations revealed a hemoglobin level of 76 g/L. Gastroduodenoscopic examination showed isolated gastric fundal varices with red color signs. Abdominal contrast-enhanced computed tomography (CECT) revealed non-enhanced masses of soft-tissue density in the lesser omental and the retropancreatic areas, multiple para-aortic lymph nodes, and multiple small hypodense splenic lesions. Positron emission tomography-CT showed hypermetabolic [F-18]2-fluoro-2-deoxyglucose activity involving multiple regional lymph nodes and the bone marrow, suggestive of lymphoma. Bone marrow biopsy revealed no abnormality. Histopathological examination of a CT-guided biopsy specimen showed granulomatous inflammation with necrosis and microorganisms that stained positive with acid-fast stains. Abdominal CECT showed a decrease in the size of the lesser omental and peripancreatic masses, as well as the para-aortic lymph nodes after 4-month anti-TB therapy. CONCLUSIONS: TB should be considered among the differential diagnoses in patients with abdominal masses, isolated gastric varices, and regional lymphadenopathy. Prompt and definitive diagnosis of abdominal TB requires a coordinated approach involving laboratory tests, radiological examination, and invasive procedures for optimal decision making and management.

Sleep disturbance and psychological distress are associated with functional dyspepsia based on Rome III criteria.

BACKGROUND: Functional dyspepsia (FD) is considered a bio-psychosocial disorder. The role of psychosocial factors in FD pathogenesis remains unclear. METHODS: This study evaluated sleep quality and mood symptoms in patients with FD, assessing the associations of FD severity, disordered sleep, and psychological symptoms. One-hundred-and-fifteen adult patients with typical FD symptoms were enrolled alongside 61 healthy volunteers. Rome III criteria were used to evaluate FD symptoms; sleep disorder was assessed with the Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist-90-Revised (SCL-90R) was utilized to determine the status of depression, anxiety and other psychological symptoms. RESULTS: PSQI scores and nine symptomatic dimensions of SCL-90R were significantly higher in FD patients than in controls. Multiple logistic regression indicated that lower BMI, lower level of education, and sleep disturbance were independently associated with FD and FD subgroups. Hostility and phobic anxiety were independent risk factors for FD. Further analysis showed that hostility was an independent risk factor for both FD subgroups, and somatization and additional psychiatric symptoms for epigastric pain syndrome. CONCLUSIONS: We found that FD was associated with sleep disorder and psychopathological factors. These findings suggest that implementing sleeping and/or psychological therapies may help reduce FD symptoms.

LncRNA MALAT1 is up-regulated in diabetic gastroparesis and involved in high-glucose-induced cellular processes in human gastric smooth muscle cells.

Recent years, widespread long non-coding RNAs (lncRNAs) were identified and known as regulator of gene expression. Diabetic gastroparesis (DGP) is one of the most common chronic complications of diabetes mellitus. There was no research reported the role of lncRNAs in DGP. In this study, we firstly established a rat model of DGP by STZ injection. Then, we detected the expression of MALAT1 and found that expression of MALAT1 was up-regulated in rat model of DGP, comparing to the control group (P < .01). Furthermore, we revealed that MALAT1 expression was increased in the samples from diabetic patients with DGP symptoms, in comparison with the control. In addition, we demonstrated that the inhibition of MALAT1 increased the expression of α-SMA and SM myosin heavy chains, reduced the cell viability, inhibited the potential of cell migration and induced cell apoptosis in human gastric smooth muscle cells (SMCs). Ultimately, we found that the regulation of MALAT1 expression modulated the function of high-glucose stimulation in human gastric SMCs. Therefore, our study firstly indicated that MALAT1 was up-regulated in DGP and played an important role in the pathogenesis of DGP.

Down-regulation of lncRNA MEG3 promotes hypoxia-induced human pulmonary artery smooth muscle cell proliferation and migration via repressing PTEN by sponging miR-21.

Hypoxia-induced pulmonary hypertension is a life-threatening disease arising from a progressive increase in pulmonary vascular resistance, irreversible pulmonary vascular remodeling and resulting in right ventricular failure. Recent studies suggested that pulmonary artery smooth muscle cell proliferation and migration played an important role in the pathogenesis of hypoxia-induced pulmonary hypertension. However, the mechanisms of hypoxia-induced pulmonary hypertension are complicated and largely unclear. In this study, we discovered that lncRNA MEG3 was down-regulated in human pulmonary artery smooth muscle cell in hypoxia, and inhibition of MEG3 promoted the cell proliferation and cell migration in both normal and hypoxia condition. Further study demonstrated that MEG3 exerted its function via regulation of miR-21 expression in both normal and hypoxia condition. In addition, we displayed the modulation of PTEN by miR-21 and their role in hypoxia. Ultimately, our study illustrated that MEG3 exerts its role via miR-21/PTEN axis in human pulmonary artery smooth muscle cell under both normal and hypoxia conditions.

An association between the endothelial nitric oxide synthase gene G894T polymorphism and premature coronary artery disease: a meta-analysis.

Previous epidemiological studies have suggested that genetic factors are more likely to influence the development of premature coronary artery disease (CAD) than disease in older patients. Several studies have evaluated the association between the G894T polymorphism located in an exon of endothelial nitric oxide synthase (eNOS) and the risk of premature CAD. However, the findings were inconsistent. Thus, we performed a meta-analysis to clarify the association; we conducted both overall and subgroup analyses. Odds ratios and 95% confidence interval were calculated to evaluate the association between the G894T polymorphism and the risk of premature CAD. Overall analysis revealed a significant association. Subgroup analysis in terms of ethnicity revealed a significant association, in all models evaluated, between the G894T polymorphism and susceptibility to premature CAD in mixed population. In contrast, no such association was evident in Caucasians and Asians. On further subgroup analysis based on the premature CAD subtypes, we found that the G894T polymorphism was correlated with premature myocardial infarction (MI) but not with premature CAD without MI. In conclusion, we confirmed that the eNOS G894T polymorphism is a risk factor for premature CAD, particularly in those suffering premature MI.

Atorvastatin treatment modulates p16 promoter methylation to regulate p16 expression.

Intimal hyperplasia, the key event of arterial restenosis, is a result of cell proliferation and cell migration. Atorvastatin exerts an inhibitory effect on cell proliferation and migration, but the mechanism remains largely unknown. p16, as a well-known tumor suppressor, was also reported to suppress cell growth and migration, but with an unclear mechanism. In this study, we demonstrated that atorvastatin represses cell proliferation and migration in vascular smooth muscle cells (VSMCs) and that this process is mediated by p16. Furthermore, we found that DNA methylation in the p16 promoter was reduced and p16 expression was restored in VSMCs treated with 5-aza-2'-deoxycytidine or atorvastatin. However, the effect was absent when DNA methyltransferase 1 (DNMT1) was knocked down with RNA interference. These observations demonstrated that atorvastatin regulates p16 expression via DNMT1-induced DNA methylation in the p16 promoter. In addition, we found that the mitogen-activated protein kinase (MAPK) pathway was involved in the regulation of p16 by DNMT1, and MAPK inhibitors partially released the effects of atorvastatin on p16 and DNMT1. Finally, we illustrated that atorvastatin inhibits neointima formation and modulates p16 expression in balloon catheter-injured rat carotid artery. Taken together, we demonstrated that atorvastatin inhibits neointima formation through inducing p16 expression by affecting DNA methylation in the p16 promoter region.

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro.

OBJECTIVES: To evaluate the role of exogenous interleukin-9 (IL-9) in the growth, proliferation and activity of interstitial cells of Cajal (ICCs) cultured in vitro, and to assess its role in maintaining the functions of ICCs. METHODS: ICCs of murine gastric antrum were isolated and cultured in vitro. ICCs were identified with c-Kit and ANO1 immunofluorescent antibodies. Both fluorescence microscope and confocal microscopy were used to observe the effects of IL-9 on the growth, proliferation and activity of ICCs in cultured in vitro. ICCs were loaded with fluorescence probe Fluo-3/AM and the fluorescence of intracellular calcium concentration ([Ca2+]i) was measured by confocal microscopy. The effects of exogenous IL-9 on the sulfated cholecystokinin octapeptide (CCK-8S)-evoked [Ca2+]i elevation were observed by confocal microscopy. RESULTS: Immunofluorescence results confirmed the successful separation and culture of ICCs in vitro. IL-9 in concentrations ranging from 0.02 to 1 µg/ml promoted the growth, proliferation and activity of ICCs in culture, and ICCs grew best with 0.5 mg/ml of IL-9. The presence of IL-9 could significantly increase the CCK-8S-evoked [Ca2+]i oscillation, which is probably caused by facilitating the maintenance of the functions of ICCs under suitable conditions for culture. CONCLUSION: IL-9 could promote the growth, proliferation and activity of ICCs, reinforce the CCK-8S-induced [Ca2+]i increment in ICCs, and facilitate the maintenance of the functions of ICCs under suitable culture condition.