[Determination of four amide synthetic cannabinoid isomers by ultra-high performance liquid chromatography-high resolution mass spectrometry].

Isomerization commonly occurs in synthetic cannabinoids (SCs). Owing to the few differences in their structure and properties, it is difficult to simultaneously separate and identify them. Thus, the identification of synthetic cannabinoids is challenging, posing a threat to public security. This study aims to separate and identify four SCs, which are 2-[1-(5-fluoropentyl)-1H-indole-3-formylamino]-3,3-dimethylbutyrate methyl ester (5F-MDMB-PICA), 2-[1-(5-fluoropentyl)-1H-indole-3-formylamino]-3-methylbutyrate ethyl ester (5F-EMB-PICA), N-(1-amino-2,2-dimethyl-1-oxobutyl-2-yl)-1-butyl-1H-indazole-3-formamide (ADB-BINACA), N-(1-carbamoyl-2-methylpropyl)-1-pentyl indazole-3-formamide (AB-PINACA).Supercritical fluid chromatography-mass spectroscopy (SFC-MS) can realize the effective separation of some cannabinoid isomers. However, most laboratories are not equipped with SFC-MS systems. Ultra-high performance liquid chromatography-high resolution mass spectroscopy (UHPLC-HRMS) effectively combines the excellent efficient separation characteristics of liquid chromatography and the powerful qualitative ability of mass spectrometry. It is a commonly used technical method for the detection of amide synthetic cannabinoids and their metabolites in vivo and in vitro because of its advantages of high accuracy and efficiency. Liquid chromatography allows the separation of tested components by exploiting the difference in the partition coefficients between the mobile and stationary phases. When the two phases are in relative motion, the tested components are divided between the two phases, facilitating the separation and analysis of each component. Although the difference in the polarities of the tested amide synthetic cannabinoid isomeric substances is extremely small, liquid chromatography can induce a strong separation effect. The advantages of UHPLC-HRMS include high resolution imparted by mass spectrometry and high sensitivity, allowing its application in the qualitative analysis of various substances. Through UHPLC-HRMS, trace analytes at the nanogram scale as well as pure drugs and their metabolites in biosamples can be detected. This study proposed a method for the determination of two pairs of amide synthetic cannabinoid isomers-5F-EMB-PICA and 5F-MDMB-PICA, ADB-BINACA and AB-PINACA-through UHPLC-HRMS. A Hypersil GOLD C18 column (100 mm×2.1 mm, 1.9 µm) was selected for separation via liquid chromatography, and gradient elution was performed with methanol containing 0.1% formic acid and a 0.1% formic acid aqueous solution containing 10 mmol/L ammonium formate. Full scan/data-dependent secondary mass spectrometry (Full MS/dd-MS2) was conducted in the positive ion mode for detection. The results indicated that the four synthetic cannabinoid isomers could be accurately detected under the abovementioned conditions. The resolution between 5F-EMB-PICA and 5F-MDMB-PICA was 2.06, while that between ADB-BINACA and AB-PINACA was 1.22, indicating the effective separation and detection of both pairs. Furthermore, method validation was conducted to ensure the accuracy of the proposed method. The relationship of the four amide synthetic cannabinoid isomers exhibited excellent linearity. The correlation coefficients (R2) were >0.99. Moreover, the matrix effects of the four SCs in hair samples were between 88.67% and 111.76% and the recoveries were 96.23%-105.11%. The intra-day and inter-day precisions (RSDs) were <10%. The proposed method was used to identify the case materials. AB-PINACA was detected in a hair sample at a content of 0.73 µg/g. 5F-MDMB-PICA was detected in a tobacco sample at a content of 11.3 mg/g. The results indicate that the proposed method can be used for the examination of practical samples conducted by public security organizations. This study provides a reference method for the identification of synthetic cannabinoid isomers.

Advances in The Diagnosis and Treatment of Achalasia of The Cardia: a Review.

Idiopathic achalasia is an esophageal motor disorder characterized by the loss of the lower esophageal sphincter ganglion, resulting in impaired lower esophageal relaxation and absence of esophageal peristalsis. Patients commonly present with progressive dysphagia accompanied by reflux, heartburn, retrosternal pain, and severe weight loss. Diagnosis is primarily based on the patient's chief complaints, barium esophagography, and the most recent high-resolution manometry. Endoscopic assessment and endoscopic ultrasonography also have significant value with regard to the exclusion of esophageal anatomical lesions, neoplastic diseases, and pseudoachalasia. However, as most patients with achalasia demonstrate a gradual onset, early diagnosis is difficult. Currently, treatment of idiopathic achalasia, including pneumatic dilation, stent placement, and surgical myotomy, is aimed at reducing lower esophageal sphincter pressure and relieving the symptoms of dysphagia. Peroral endoscopic myotomy has gradually become the mainstream treatment because it causes less trauma and has a rapid recovery rate. This article reviews the main methods of diagnosis and treatment of achalasia, with an emphasis on the potential of peroral endoscopic myotomy and the advancements of immunotherapy for achalasia.

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.

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.

Advances in the Prevention and Treatment of Esophageal Stricture after Endoscopic Submucosal Dissection of Early Esophageal Cancer.

Endoscopic submucosal dissection (ESD) has become the main treatment for early esophageal cancer. While treating the disease, ESD may also cause postoperative esophageal stricture, which is a global issue that needs resolution. Various methods have been applied to resolve the problem, such as mechanical dilatation, glucocorticoids, anti-scarring drugs, and regenerative medicine; however, no standard treatment regimen exists. This article describes and evaluates the strengths and limitations of new and promising potential strategies for the treatment and prevention of esophageal strictures.

Comparison of endoscopic ultrasound-guided hepaticogastrostomy and the antegrade technique in the management of unresectable malignant biliary obstruction: study protocol for a prospective, multicentre, randomised controlled trial.

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is used after failed endoscopic retrograde cholangiopancreatography. Based on existing studies, intrahepatic (IH) approaches are preferred in patients with dilated IH bile ducts. Both ultrasound-guided hepaticogastrostomy (EUS-HGS) and ultrasound-guided antegrade treatment (EUS-AG) are appropriate for patients with unreachable papillae. Nevertheless, there have been no direct comparisons between these two approaches. Therefore, we aim to evaluate and compare the safety and efficiency of EUS-HGS and EUS-AG in patients with an unreachable papilla. METHODS: This is a prospective, randomised, controlled, multicentre study with two parallel groups without masking. One hundred forty-eight patients from three hospitals who met the inclusion criteria will be randomly assigned (1:1) to undergo either EUS-HGS or EUS-AG for relief of malignant biliary obstruction. The final study follow-up is scheduled at 1 year postoperatively. The primary endpoint is efficiency, described by technical and clinical success rates of EUS-HGS and EUS-AG in patients with unreachable papillae. The secondary endpoints include stent patency, overall survival rates, complication rates, length of hospital stays, and hospitalisation expenses. The chi-square test, Kaplan-Meier methods, log-rank test, and Cox regression analysis will be used to analyse the data. DISCUSSION: To our knowledge, this is the first study to compare these two EUS-BD approaches directly using a multicentre, randomised, controlled trial design. The clinical economic indexes will also be compared, as they may also affect the patient's choice. The result may contribute to establishing a strategic guideline for choosing IH EUS-BD approaches. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900020737 . Registered on 15 January 2019.