Four-Component Reaction Access to Nitrile-Substituted All-Carbon Quaternary Centers.

A four-component reaction strategy for access to acyclic nitrile-substituted all-carbon quaternary centers is disclosed. In the presence of a DABCO-based ionic liquid catalyst, the reactions proceed smoothly with a wide range of substrates efficiently to deliver nitrile-substituted all-carbon quaternary centers under mild reaction conditions. This protocol is further demonstrated as an efficient method for the construction of contiguous all-carbon quaternary centers. All the reactions are easily operated in a green manner, producing water as the only byproduct. Some of the products show excellent activity against specific fungi.

Artificial intelligence for detecting superficial esophageal squamous cell carcinoma under multiple endoscopic imaging modalities: A multicenter study.

BACKGROUND AND AIM: Diagnosis of esophageal squamous cell carcinoma (ESCC) is complicated and requires substantial expertise and experience. This study aimed to develop an artificial intelligence (AI) system for detecting superficial ESCC under multiple endoscopic imaging modalities. METHODS: Endoscopic images were retrospectively collected from West China Hospital, Sichuan University as a training dataset and an independent internal validation dataset. Images from other four hospitals were used as an external validation dataset. The AI system was compared with 11 experienced endoscopists. Furthermore, videos were collected to assess the performance of the AI system. RESULTS: A total of 53 933 images from 2621 patients and 142 videos from 19 patients were used to develop and validate the AI system. In the internal and external validation datasets, the performance of the AI system under all or different endoscopic imaging modalities was satisfactory, with sensitivity of 92.5-99.7%, specificity of 78.5-89.0%, and area under the receiver operating characteristic curves of 0.906-0.989. The AI system achieved comparable performance with experienced endoscopists. Regarding superficial ESCC confined to the epithelium, the AI system was more sensitive than experienced endoscopists on white-light imaging (90.8% vs 82.5%, P = 0.022). Moreover, the AI system exhibited good performance in videos, with sensitivity of 89.5-100% and specificity of 73.7-89.5%. CONCLUSIONS: We developed an AI system that showed comparable performance with experienced endoscopists in detecting superficial ESCC under multiple endoscopic imaging modalities and might provide valuable support for inexperienced endoscopists, despite requiring further evaluation.

Risk factors for distal migration of biliary plastic stents and related duodenal injury.

BACKGROUND: The risk factors of duodenal injury from distal migrated biliary plastic stents remain uncertain. The aim of this study was to determine the risk factors of distal migration and its related duodenal injury in patients who underwent placement of a single biliary plastic stent for biliary strictures. METHODS: We retrospectively reviewed all patients with biliary strictures who underwent endoscopic placement of a single biliary plastic stent from January 2006 to October 2017. RESULTS: Two hundred forty-eight patients with 402 endoscopic retrograde cholangiopancreatography procedures were included. The incidence of distal migration was 6.2%. The frequency of duodenal injury was 2.2% in all cases and 36% in cases with distal migration. Benign biliary strictures (BBS), length of the stent above the proximal end of the stricture (> 2 cm), and duration of stent retention (< 3 months) were independently associated with distal migration (p = 0.018, p = 0.009, and p = 0.016, respectively). Duodenal injury occurred more commonly in cases with larger angle (≥ 30°) between the distal end of the stent and the centerline of the patient's body (p = 0.018) or in cases with stent retention < 3 months (p = 0.031). CONCLUSIONS: The risk factors of distal migration are BBS and the length of the stent above the proximal end of the stricture. The risk factor of duodenal injury due to distal migration is large angle (≥ 30°) between the distal end of the stent and the centerline of the patient's body. Distal migration and related duodenal injury are more likely to present during the early period after biliary stenting.

p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation.

The ubiquitin-proteasome system (UPS) and autophagy are two distinct and interacting proteolytic systems. They play critical roles in cell survival under normal conditions and during stress. An increasing body of evidence indicates that ubiquitinated cargoes are important markers of degradation. p62, a classical receptor of autophagy, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1-Nrf2 pathway. It is involved in the proteasomal degradation of ubiquitinated proteins. When the cellular p62 level is manipulated, the quantity and location pattern of ubiquitinated proteins change with a considerable impact on cell survival. Altered p62 levels can even lead to some diseases. The proteotoxic stress imposed by proteasome inhibition can activate autophagy through p62 phosphorylation. A deficiency in autophagy may compromise the ubiquitin-proteasome system, since overabundant p62 delays delivery of the proteasomal substrate to the proteasome despite proteasomal catalytic activity being unchanged. In addition, p62 and the proteasome can modulate the activity of HDAC6 deacetylase, thus influencing the autophagic degradation.

Artificial intelligence-assisted esophageal cancer management: Now and future.

Esophageal cancer poses diagnostic, therapeutic and economic burdens in high-risk regions. Artificial intelligence (AI) has been developed for diagnosis and outcome prediction using various features, including clinicopathologic, radiologic, and genetic variables, which can achieve inspiring results. One of the most recent tasks of AI is to use state-of-the-art deep learning technique to detect both early esophageal squamous cell carcinoma and esophageal adenocarcinoma in Barrett's esophagus. In this review, we aim to provide a comprehensive overview of the ways in which AI may help physicians diagnose advanced cancer and make clinical decisions based on predicted outcomes, and combine the endoscopic images to detect precancerous lesions or early cancer. Pertinent studies conducted in recent two years have surged in numbers, with large datasets and external validation from multi-centers, and have partly achieved intriguing results of expert's performance of AI in real time. Improved pre-trained computer-aided diagnosis algorithms in the future studies with larger training and external validation datasets, aiming at real-time video processing, are imperative to produce a diagnostic efficacy similar to or even superior to experienced endoscopists. Meanwhile, supervised randomized controlled trials in real clinical practice are highly essential for a solid conclusion, which meets patient-centered satisfaction. Notably, ethical and legal issues regarding the black-box nature of computer algorithms should be addressed, for both clinicians and regulators.

Endoscopic palliative resection of a giant 26-cm esophageal tumor: A case report.

BACKGROUND: Esophageal carcinosarcoma, usually presenting as a pedunculated polypoid mass, is a rare malignancy with coexisting sarcomatoid and carcinomatous components. Its imaging and endoscopic characteristics are similar to those of leiomyosarcoma, liposarcoma and so forth. The diagnosis needs histological confirmation. Surgical resection is the traditional therapy. Endoscopic resection is minimally invasive but still controversial. This paper reports the case of a patient with a giant esophageal carsinosarcoma who underwent a palliative endoscopic resection. CASE SUMMARY: A 55-year-old male patient presented with dysphagia and weight loss for 1 mo. Imaging and endoscopy showed a gray-white, polypoid, stalk-like mass, with a bulky pedicle located in the middle and lower esophagus. The mass almost filled the whole esophageal lumen, but the endoscope could still pass through. Despite the suspicion of a malignancy, repeated biopsies indicated necrosis and inflammation. After multidisciplinary team consultation, an endoscopic resection to diagnose and relieve the obstruction was recommended. The pedicle of the mass was cut off, the bleeding was stopped, and the mass was cut into pieces and pulled out. The mass was 26 cm × 5 cm × 4 cm in size. The final diagnosis was esophageal carcinosarcoma. No postoperative complications occurred. After 1 mo, the patient gained 6 kg and endoscopic reexamination revealed no obstruction. Radical surgery with lymph node dissection was carried out successfully. This lesion was the largest endoscopically resected esophageal carcinosarcoma reported to date. CONCLUSION: Endoscopic palliative resection can help obtain adequate tissue for diagnosis and relieve obstructions in patients with giant esophageal carcinosarcoma.

Epidemiological features of gastroenteropancreatic neuroendocrine tumors in Chengdu city with a population of 14 million based on data from a single institution.

AIM: Recent studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in the United States as well as the European studies demonstrate an increasing GEP-NETs incidence. Most information on the epidemiology of neuroendocrine tumors comes from western countries. However, the epidemiological profile of GEP-NETs in West China is still unclear. The aim of study was to reflect the regional features of GEP-NETs in Chengdu city of West China based on data from a single institution. METHODS: West China Hospital (WCH), the largest university hospital located in Chengdu (West China) with population of 14.04 million, has established a serial of databases in recent years. According to the data from Medical Records Section of WCH and Chengdu Health Bureau, the total patients per year in WCH covered about 25.6-28% patients of Chengdu city during the 5 years. Therefore, we have used GEP-NETs diagnosed in WCH from 2009 to 2013 to reflect the regional epidemiological profile of GEP-NETs. RESULTS: GEP-NETs proportion in WCH increased 1.6-folds during past 5 years from 1.28/10(5) to 2.03/10(5) , P < 0.05. The average duration of symptom before diagnosis was 16.8 months. About 46.6% (115/248) of GEP-NETs were metastatic. Seventy-seven percent (190/248) of patients were over 40 years. Proportions of GEP-NETs from primary sites were rectum 30.6% (76/248), pancreas 23.4% (58/248), gastric 13.3% (33/248) and esophagus 11.3% (28/248). Proportions of insulinoma, vipoma and nonfunctional pancreatic neuroendocrine tumors (P-NETs) were 43.1% (25/58), 1.7% (1/58) and 55.2% (32/58) separately in the P-NETs. CONCLUSIONS: There is a distinct epidemiologic profile between West China and western countries based on a single institution data. The delayed diagnosis reflects inadequate disease awareness of GEP-NETs and paucity of research funding.

[Effect of bcl-2 antisense oligonucleotides on multidrug resistance of cultured uveal melanoma cells].

OBJECTIVE: To evaluate the chemotherapeutic sensitivity of uveal melanoma in vitro and reverse its drug resistance by the delivery of bcl-2 antisense oligodeoxynucleotide (AS-ODN). METHODS: The drug sensitivity tests of primary cultured uveal melanoma cells toward 5-flurouracil (5-FU), thiophosphamide (TSPA), cisplatin (DDP), adriamycin (ADM), vinblastine (VLB), dacarbazine (DTIC) were performed with 3, -4, 5 dimethyliazol-2,5 diphenyl tetrazolium bromide (MTT). AS-ODN bcl-2 were delivered with cationic lipid to down-regulate bcl-2 expression. Immunohistochemistry and Western-blot methods were used to detect bcl-2 expression. According to the principle of multi-drug mutual action, the influence of anti-apoptosis gene bcl-2 on tumor cell drug sensitivity was measured. RESULTS: Uveal melanoma was resistant to different chemotherapeutic drugs in different degrees. AS-ODN bcl-2 could down-regulate bcl-2 expression, was synergetic with all tested drugs and partially reversed the multi-drug resistance. CONCLUSIONS: Clinically, with ordinary dosages the above 6 drugs have little cytotoxicity to uveal melanoma cells, bcl-2 over-expression is associated with multi-drug resistance and AS-ODN bcl-2 can partially reverse the multi-drug resistance.

Somatostatin analogues do not prevent carcinoid crisis.

BACKGROUND: Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis. MATERIALS AND METHODS: PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013. RESULTS: Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/ surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15). CONCLUSIONS: SSTA was not helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.