Stent placement to prevent strictures after esophageal endoscopic submucosal dissection: a systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) is an important method for the treatment of early esophageal cancer. However, post-procedure stenosis is one of the most common long-term complications. This meta-analysis aimed to investigate whether stent placement is effective in the stenosis prevention, and which type of stent would be more effective. A systematic and electronic search of clinical trials and observational studies conducted before March 2020 on the efficacy of stent placement in preventing esophageal stricture after ESD was performed. Search terms included "ESD," "esophageal stenosis," "esophageal stricture," and "stents." We conducted a bias risk assessment of the eligible reports and a meta-analysis of the data using Revman 5.3 software. We included two randomized controlled trials (RCTs) and a prospective cohort study involving 163 patients with esophageal mucosal defects encompassing at least three-quarters of the esophagus circumference after ESD. The meta-analysis results showed that post-ESD stenosis rates (RR, 0.37; 95% CI, 0.22-0.64; P = 0.0003) and the number of endoscopic balloon dilations (EBDs) (MD, -1.74; 95% CI, -2.46 to -1.01; P < 0.00001) were reduced in the pooled analysis of three studies, indicating that stent placement was effective for stenosis prevention, especially a polyglycolic acid (PGA) sheet combined with stent placement can prevent stenosis (RR, 0.41; 95% CI, 0.23-0.74; P = 0.003) and reduce the number of EBDs (MD, -1.65; 95% CI, -2.40 to -0.90; P < 0.0001) significantly. Stent placement can reduce the rate of esophageal stenosis after ESD, especially when stents are covered with PGA sheets. However, more high-quality, low-bias RCTs with a sufficient sample size are needed to demonstrate its effectiveness.

Interaction Effects between Doxorubicin and Hernandezine on the Pharmacokinetics by Liquid Chromatography Coupled with Mass Spectrometry.

Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of the interaction of HER and DOX on pharmacokinetics. Male Sparague-Dawley rats were randomly divided into three groups: a single DOX group, a single HER group, and a combination group. Plasma concentrations of DOX and HER were determined by the LC-MS/MS method at specified time points after administration, and the main pharmacokinetic parameters were estimated. The results showed that there were significant differences in the Cmax and AUC0-∞ of DOX in the single drug group and combined drug group, indicating that HER could improve the absorption of DOX. However, DOX in combination, in turn, reduced the free drug concentration of HER, possibly because DOX enhanced the HER drug-protein binding effect. The results could be used as clinical guidance for DOX and HER to avoid adverse reactions.

Liraglutide reduces the body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients.

AIM: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. METHODS: A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with liraglutide once daily for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Statistical analyses were performed using SPSS software package version 11.5 for Windows. RESULTS: Liraglutide treatment caused significant reduction of the mean body weight (from 86.61±14.09 to 79.10±13.55 kg) and waist circumference (from 101.81±13.96 to 94.29±14.17 cm), resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss above 10% in 34.06% patients, who had significant lower plasma creatinine levels. Baseline waist circumference, BMI and HOMA-IR were independently correlated with the body weight loss. Furthermore, liraglutide treatment significantly decreased HbA1c levels (from 8.66%±2.17% to 6.92%±0.95%) with HbA1c<7.0% in 35.37% patients, who had a significantly lower baseline level of HbA1c, but higher baseline levels of C peptide and glucagon. Moreover, liraglutide treatment resulted in greater body weight loss in patients with a long duration of diabetes, and better glycemic control in patients with a short duration of diabetes. CONCLUSION: Liraglutide significantly reduces body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Patients with apparent visceral obesity, insulin resistance and a long duration of diabetes may have greater body weight loss; whereas patients with high insulin-secreting ability, hyperglucagonemia, and short-duration diabetes may obtain better glycemic control with liraglutide.

Endoscopic full-thickness resection using an over-the-scope device: A prospective study.

BACKGROUND: Endoscopic submucosal dissection to treat mucosal and submucosal lesions sometimes results in low rates of microscopically margin-negative (R0) resection. Endoscopic full-thickness resection (EFTR) has a high R0 resection rate and allows for the definitive diagnosis and treatment of selected mucosal and submucosal lesions that are not suitable for conventional resection techniques. AIM: To evaluate the efficacy and safety of EFTR using an over-the-scope clip (OTSC). METHODS: This prospective, single-center, non-randomized clinical trial was conducted at the endoscopy center of Shengjing Hospital of China Medical University. The study included patients aged 18-70 years who had gastric or colorectal submucosal tumors (SMTs) (≤ 20 mm in diameter) originating from the muscularis propria based on endoscopic ultrasound (EUS) and patients who had early-stage gastric or colorectal cancer (≤ 20 mm in diameter) based on EUS and computed tomography. All lesions were treated by EFTR combined with an OTSC for wound closure between November 2014 and October 2016. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. RESULTS: A total of 68 patients (17 men and 51 women) with an average age of 52.0 ± 10.5 years (32-71 years) were enrolled in this study, which included 66 gastric or colorectal SMTs and 2 early-stage colorectal cancers. The mean tumor diameter was 12.6 ± 4.3 mm. The EFTR procedure was successful in all cases. The mean EFTR procedure time was 39.6 ± 38.0 min. The mean OTSC defect closure time was 5.0 ± 3.8 min, and the success rate of closure for defects was 100%. Histologically complete resection (R0) was achieved in 67 (98.5%) patients. Procedure-related adverse events were observed in 11 (16.2%) patients. The average post-procedure length of follow-up was 48.2 ± 15.7 mo. There was no recurrence during follow-up. CONCLUSION: EFTR combined with an OTSC is an effective and safe technique for the removal of select subepithelial and epithelial lesions that are not amenable to conventional endoscopic resection techniques.

Comprehensive review of diagnostic modalities for early chronic pancreatitis.

Chronic pancreatitis (CP) is a progressive condition caused by several factors and characterised by pancreatic fibrosis and dysfunction. However, CP is difficult to diagnose at an early stage. Various advanced methods including endoscopic ultrasound based elastography and confocal laser endomicroscopy have been used to diagnose early CP, although no unified diagnostic standards have been established. In the past, the diagnosis was mainly based on imaging, and no comprehensive evaluations were performed. This review describes and compares the advantages and limitations of the traditional and latest diagnostic modalities and suggests guidelines for the standardisation of the methods used to diagnose early CP.

Endoscopic fenestration in the diagnosis and treatment of delayed anastomotic submucosal abscess: A case report and review of literature.

BACKGROUND: Abscess formation is one of the complications after radical resection of rectal cancer; cases with delayed postoperative anastomotic abscess are rare. Here, we report a rare case of postoperative anastomotic abscess with a submucosal neoplasm appearing after rectal surgery. Ultimately, the patient was diagnosed and treated by endoscopic fenestration. In addition, we review the literature on the appearance of an abscess as a complication after rectal cancer surgery. CASE SUMMARY: A 57-year-old man with a history of rectal malignancy resection complained of a smooth protuberance near the anastomotic stoma. Endoscopic ultrasonography revealed a hypoechoic structure originating from the muscularis propria, and a submucosal tumor was suspected. The patient was subsequently referred to our hospital and underwent pelvic contrast-enhanced computed tomography, which revealed no thickening or strengthening of the anastomotic wall. In order to clarify the origin of the lesion and obtain the pathology, endoscopic fenestration was performed. After endoscopic procedure, a definitive diagnosis of delayed anastomotic submucosal abscess was established. The patient achieved good recovery and prognosis after the complete clearance of abscess. CONCLUSION: Endoscopic fenestration may be safe and effective for the diagnosis/treatment of delayed intestinal smooth protuberance after rectal cancer surgery.

Endoscopic ultrasound-measured muscular thickness of the lower esophageal sphincter and long-term prognosis after peroral endoscopic myotomy for achalasia.

BACKGROUND: People with achalasia typically have a thick lower esophageal muscularis propria (LEMP), and peroral endoscopic myotomy (POEM) has been effective in treating most patients. LEMP thickness may be associated with the outcomes and prognosis after POEM. However, more evidence is needed regarding the relationship between LEMP thickness and patient prognosis after POEM. AIM: To assess the association between LEMP thickness, measured using endoscopic ultrasound (EUS), and long-term prognosis, especially relapse, after POEM for achalasia. METHODS: All medical records, including EUS data, of patients who underwent POEM to treat achalasia at Shengjing Hospital of China Medical University from January 2012 to September 2018 were retrospectively reviewed. LEMP thickness was measured by EUS, and a thickness of ≥ 3 mm was defined as thickened. The severity of patient symptoms was evaluated using the Eckardt score. Relapse was defined as a 3-point rise in the Eckardt score after a period of clinical remission. The relationship between patient characteristics, muscle thickness, and recurrence was analyzed. RESULTS: Eighty-two patients (32 males and 50 females, aged 17-78 years) and 85 POEM procedures were included. In total, 76.8% (63/82 patients) of patients had a thickened muscularis propria. Older age and longer disease course were associated with muscularis propria thickening (P < 0.05). The mean postoperative follow-up time was 35.4 ± 17.2 mo (range, 8-87.5 mo) in 60 patients. Five patients with Eckardt scores > 3 refused further management after their symptoms were relieved. The relapse rate was 12.73% (7/55 cases). Five patients, four of whom had muscularis propria thickening, had disease recurrence within 12 mo after the procedure. Achalasia relapsed in one patient who had a thickened muscularis propria after 24 mo and in another patient who did not have a thickened muscularis propria after 30 mo. Patients with recurrence were typically younger and had a shorter disease course (P < 0.05). The relapse rate in patients with a non-thickened muscularis propria tended to be higher (18.2%, 2/11 patients) than that in patients with a thickened muscularis propria (11.4%, 5/44 patients), although no significant difference was found. Age (hazard ratio = 0.92; 95% confidence interval: 0.865-0.979; P < 0.05) and being male (hazard ratio = 7.173; 95% confidence interval: 1.277-40.286; P < 0.05) were identified as risk factors for symptomatic recurrence by multivariable analysis using the Cox model. CONCLUSION: Patients with a thickened muscularis are typically older and have a longer disease course. Younger age and the male sex are associated with increased recurrence. Patients with a thin muscularis propria may be prone to relapse, although further validation is needed.

[Effects of methylation status of CpG islands on results of luciferase reporter assay].

OBJECTIVE: To investigate the effects of methylation status of CpG islands of endogenous E-cadherin (CDH1) gene on the promoter activity of corresponding genes in reporter assays. METHODS: The methylation statuses of CpG island of CDH1 in 8 different cell lines were detected by methylation-specific PCR. CDH1 protein was analyzed by Western blotting. Two sets of pGL3 reporter vectors with different genotypes/haplotypes of the CDH1 promoter were constructed [ pGL3-A(-73)/-C(-73) pGL3-H1/-H4] and used to transfect these cell lines. The differences between these promoter reporter vectors were analyzed by t-test. RESULTS: (1) CDH1 CpG island was unmethylated in AGS, MCF7, MKN74, and PC-3 cell lines, expressed in MCF7, MKN74, and PC-3, but not in AGS. Expression of CDH1 was silenced by methylation in HeLa, BGC823, A549, and RKO cell lines. (2) In the four CDH1-unmethylated MCF7, MKN74, PC-3, and AGS cell lines, the promoter activities of pGL3-C(-73), (as 0.78 +/- 0.10, 0.17 +/- 0.01, 0.11 +/- 0.01, 1.19 +/- 0.18) were significantly higher than those of pGL3-A(-73) (as 0.30 +/- 0.08, 0.07 +/- 0.01, 0.07 +/- 0.01, 0.39 +/- 0.04) (t values are -6.298, - 12.349, -8.128, -7.388, and P <. 0.1). However, in the four CDH1-methylated HeLa, BGC823, A549, and RKO cell lines, the promoter activity of pGL3-C(-73) (as 0.09 +/- 0.02, 0.13 +/- 0.02, 0.05 +/- 0.01, 0.01 +/- 0.00) was significantly lower than that of pGL3-A(-73) (as 0.16 +/- 0.01, 0.25 +/- 0.01, 0.11 +/- 0.03, 0.03 +/- 0.00) (t valued at 5.958, 11.189, 3.661, 13.866, and P<0.05). (3) In the unmethylated MKN74 and methylated RKO cell lines, the promoter activities of pGL3-H1/-H4 were obviously and contrarily different (as 1.57 +/- 0.23/0.94 +/- 0.06 and 0.38 +/- 0.02/0.50 +/- 0.04, t values were 4.577 and -4.915, P values were 0.010 and 0.003). CONCLUSION: The methylation status of CpG island of the target gene in the tested cell lines affects the promoter activity in Reporter Assay significantly. The most active one may be the most suppressive one.

[Methylation specific binding activity of zinc finger protein Kaiso].

OBJECTIVE: To compare binding activity of different zinc finger domain of human Kaiso with methylated CpG. METHODS: pGEX constructs with different human Kaiso domain were generated and then corresponding fusion proteins were induced and purified. Electrophoretic mobility shift assays were applied to evaluate the binding activity of fusion proteins with methylated CpG. RESULTS: The purified GST-KaisoZF fusion protein (without the POZ protein binding domain) could bind with methylated CpG probe specifically, but not for three or two zinc fingers without flanking domains. CONCLUSION: Human zinc finger protein Kaiso could bind with methylated CpG specifically, only in the assistance of the neighboring flank sequence of the zinc finger domain.

Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72.

Heat stress stimulates the production of reactive oxygen species (ROS), which cause oxidative damage in the kidney. This study clarifies the mechanism by which saikosaponin-d (SSd), which is extracted from the roots of Bupleurum falcatum L, protects heat-stressed pig kidney proximal tubular (LLC-PK1) cells against oxidative damage. SSd alone is not cytotoxic at concentrations of 1 or 3 µg/mL as demonstrated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To assess the effects of SSd on heat stress-induced cellular damage, LLC-PK1 cells were pretreated with various concentrations of SSd, heat stressed at 42°C for 1 h, and then returned to 37°C for 9 h. DNA ladder and MTT assays demonstrated that SSd helped to prevent heat stress-induced cellular damage when compared to untreated cells. Additionally, pretreatment with SSd increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) but decreased the concentration of malondialdehyde (MDA) in a dose-dependent manner when compared to controls. Furthermore, real-time PCR and Western blot analysis demonstrated that SSd significantly increased the expression of copper and zinc superoxide dismutase (SOD-1), CAT, GPx-1 and heat shock protein 72 (HSP72) at both the mRNA and protein levels. In conclusion, these results are the first to demonstrate that SSd ameliorates heat stress-induced oxidative damage by modulating the activity of anti-oxidant enzymes and HSP72 in LLC-PK1 cells.

[STI571 induces apoptosis of K562 cells through down-regulation of anti-apoptotic protein Mcl-1 and Bcl-xl expression].

This study was aimed to investigate the effect of STI571, an inhibitor of tyrosine kinase, on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells as well as expression of anti-apoptotic protein Mcl-1, and to explore the possible role of Mcl-1 in apoptosis-inducing mechanism. K562 cell line was used to observe the effect of STI571 on CML cells. Proliferation and cytotoxicity were analyzed by MTT assay. The apoptotic cells were labelled with Annexin V-FITC and PI and then analyzed by flow cytometry. The expression of apoptotic-related proteins in K562 cells was determined by Western blot with specific antibodies. The results showed that STI571 significantly inhibited the proliferation and induced apoptosis of K562 cells in a dose-and time-dependent manner. Coincidently, the protein phosphorylation on tyrosine residues was reduced and the expressions of anti-apoptotic protein Mcl-1 and Bcl-xl were down-regulated after exposure to STI571. It is concluded that STI571 induces the apoptosis of CML cells by down-regulating the expressions of Mcl-1 and Bcl-xl, which suggests that Mcl-1 and Bcl-xl may play an important role in anti-apoptotic process of CML cells.