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Long non-coding RNA (lncRNA) ZFAS1 (zinc finger antisense 1) was demonstrated to play critical roles in various cancer progression. However, the functions of ZFAS in cervical cancers (CC) are unclear. Human CC cell lines were used for in vitro experiments. RT-qPCR (Real Time Quantitative PCR) was performed to detect the expression of ZFAS1, microRNA-190a-3p (miR-190a-3p) and Kruppel-like factor 6 (KLF6). Cell proliferation, invasion and migration assays were used to investigate biological behaviors of CC cells related to CC progression. The relationship of KLF6 to ZFAS1 and miR-190a-3p was analyzed by circRIP and luciferase reporter assay. In addition, in vivo experiment was carried out to explore the function of ZFAS1 in tumor growth of CC. The expression levels of ZFAS1 and KLF6 were both significantly elevated, while the expression of miR-190a-3p was inhibited in CC tumor tissues. In addition, ZFAS1 influenced CC tumor growth through miR-190a-3p. KLF6 was a target of miR-190a-3p and inhibited miR-190a-3p-induced CC tumor growth. Furthermore, KLF6 was negatively regulated by miR-190a-3p, but positively regulated by ZFAS1. Overexpression of ZFAS1 and inhibition of miR-190a-3p significantly increased the expression levels of KLF6. Finally, in vitro assays demonstrated that inhibition of ZFAS1 reduced CC tumor growth and the expression levels of KLF6, but increased the expression levels of miR-190a-3p. ZFAS1 could regulate CC pathogenesis via regulating the miR-190a-3p/KLF6 axis, which might be considered as new CC therapeutic targets.

Background Biliary papillomatosis is a rare type of papillomatosis. Depending on the location of the disease, radical surgical resection or liver transplants are the treatment of choice. These radical surgical options may be unrealistic in patients who are not surgical candidates or who are unwilling to consider surgery. Aims To evaluate the effectiveness of endoscopic electrocoagulation for the biliary papillomatosis. Methods In this case series, we report six patients with unresectable biliary papillomatosis who underwent cholangioscopic electrocoagulation using needle knife and their clinic follow up information. Results After patients received cholangioscopy with electrocoagulation of the residual biliary papilloma, the daily T-tube drainage volume increased to 200–400 ml with improvement in the drainage content and significant relief of clinical symptoms, such as jaundice and abdominal pain. Conclusion This method of using electrocoagulation to directly target and destroy tumor tissue is a safe and effective alternative for those with unresectable disease, and this method has shown to enhance T-tube drainage volume and improve patients’ overall clinical symptoms.

Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is upregulated and causes reactive astrogliosis, synaptic degeneration, and cognitive deficits in Alzheimer's disease (AD). However, the mechanism underlying the increased CIP2A expression in AD brains remains unclear. We here demonstrated that the DNA damage-related Checkpoint kinase 1 (ChK1) is activated in AD human brains and 3xTg-AD mice. ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induces reactive astrogliosis, degeneration of neurons, and exacerbation of AD through the CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1 may be a potential therapeutic approach for AD treatment.

Background: In Alzheimer’s disease (AD), activation of astrocyte participates in the development of neurodegenerative diseases through neuroinflammation and disturbs glia-neuron interaction. Cancerous Inhibitor of PP2A (CIP2A) is an endogenous PP2A inhibitor. CIP2A upregulation specifically in astrocytes causes reactive astrogliosis, synaptic degeneration and cognitive deficits. However, the underlying mechanism of CIP2A upregulation remains unclear. Methods: In 3xTg-AD mice, we determined ChK1 was activated and related to DNA damage upregulating CIP2A by WB. We transfected EGFP-ChK1 plasmid into HEK293-T cell to determine ChK1 induces CIP2A upregulation and PP2A inhibition. We incubated Aβ and infected GFAP-ChK1-LV into primary astrocytes to confirm the signaling pathway in astrocytes and astrogliosis in AD. GFAP-ChK1-AAV was injected into C57/BL6 mice to induce specific expression of target protein in astrocytes. ChK1 inhibitor (SB) was performed to reverse the ChK1 activity. Outcomes were assessed using molecular (immunofluorescent staining, Western Blot and Golgi staining) measures to estimate symptomatic pathology and behavioral (NORT, OLT, MWM and FCT) measures to assess cognitive function. For most experiments, subjects were randomly assigned to experimental groups, and data were collected under blinded experimental conditions.Results: We demonstrated that DNA damage related Checkpoint kinase 1 (ChK1) was activated in 3xTg-AD mice. ChK1-mediated CIP2A overexpression drove inhibition of PP2A and activated STAT3, then led to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induced reactive astrogliosis, degeneration of neurons and deterioration of AD through CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1 might be a potential therapeutic approach for AD treatment.Conclusions: These results suggest that ChK1 is upregulated in 3xTg-AD mice, ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis, neurodegeneration and AD-like cognitive deficits in vitro and in vivo.

Background Diabetes mellitus is an important risk factor for cardiomyopathy. Increasing oxidative stress may be one of the main factors of diabetic cardiomyopathy. A13, a newly synthesized curcumin analog, was proved to be superior to curcumin in biological activity. However, little know about how A13 performed in diabetic models. In this study, we evaluated the ability of curcumin analog A13 to alleviate oxidative stress and ameliorate fibrosis in the myocardium, and explore the underlying mechanisms. Methods Intraperitoneal injection of streptozotocin (30 mg/kg in 0.1 M sodium citrate buffer, pH 4.5) induced diabetes in high-fat fed rats. The rats were respectively treated with a daily dose of curcumin or A13 via intragastric intubation for 8 weeks. Myocardial tissue sections were stained with hematoxylin–eosin; oxidative stress was detected by biochemical assays; activation of the Nrf2/ARE pathway was detected by Western blot, immunohistochemical staining and RT-qPCR; myocardial fibrosis was identified by Western blot and Masson trichrome staining. Results Treatment with curcumin analog A13 reduced the histological lesions of the myocardium in diabetic rats. Curcumin and A13 treatment decreased the malondialdehyde level and increased the activity of superoxide dismutase in the myocardium of diabetic rats. Molecular analysis and immunohistochemical staining demonstrated that dose of 20 mg/kg of A13 could activate the Nrf2/ARE pathway. Molecular analysis and Masson staining showed that curcumin analog A13 treatment significantly ameliorated fibrosis in myocardium of these diabetic rats. Conclusion Treatment with curcumin analog A13 protects the morphology of myocardium, restores the MDA levels and SOD activity, activates the Nrf2/ARE pathway and ameliorates myocardial fibrosis in diabetic rats. It may be a useful therapeutic agent for some aspects of diabetic cardiomyopathy.

This study was aimed to develop a computer-aided diagnosis (CAD) system with deep-learning technique and to validate its efficiency on detecting the four categories of lesions such as polyps, advanced cancer, erosion/ulcer and varices at endoscopy. A deep convolutional neural network (CNN) that consists of more than 50 layers were trained with a big dataset containing 327,121 white light images (WLI) of endoscopy from 117,005 cases collected from 2012 to 2017. Two CAD models were developed using images with or without annotation of the training dataset. The efficiency of the CAD system detecting the four categories of lesions was validated by another dataset containing consecutive cases from 2018 to 2019. A total of 1734 cases with 33,959 images were included in the validation datasets which containing lesions of polyps 1265, advanced cancer 500, erosion/ulcer 486, and varices 248. The CAD system developed in this study may detect polyps, advanced cancer, erosion/ulcer and varices as abnormality with the sensitivity of 88.3% and specificity of 90.3%, respectively, in 0.05 s. The training datasets with annotation may enhance either sensitivity or specificity about 20%, p = 0.000. The sensitivities and specificities for polyps, advanced cancer, erosion/ulcer and varices reached about 90%, respectively. The detect efficiency for the four categories of lesions reached to 89.7%. The CAD model for detection of multiple lesions in gastrointestinal lumen would be potentially developed into a double check along with real-time assessment and interpretation of the findings encountered by the endoscopists and may be a benefit to reduce the events of missing lesions.

Healthcare professionals responsible for patients with gastrointestinal diseases need a particular level of nursing knowledge and abilities to ensure excellent care. This study aims to propose a set of core competencies for the gastroenterology nursing specialists (GNS) in China. This research integrates quantitative and qualitative research methods. Literature review, semistructured interview, and the Delphi approach were used to develop the core competency items of GNS in China. SPSS 16.0 was used to analyze the data. Finally, 28 of 30 experts participated in the study resulting in a consensual list containing 7 domains (clinical nursing practice, communication and collaboration, education and counseling, critical thinking, leadership, ethical and legal practice, and professional development), 23 aspects, and 66 competencies required for GNS. The authority coefficient (Cr) of the consensus was 0.77, and the Kendall (W) value of each level of competencies all scored above 0.5. Results of the study can serve as a foundation of work performance evaluation for GNS as well as promote nurses' professional development.

Bariatric surgery effectively treats morbid obesity. However, the negative effect of this surgery on the bone is concerning. The aim of this meta-analysis was to investigate the fracture risk associated with bariatric surgery in morbidly obese subjects. Relevant studies published from database inception to September 2017 were identified in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to evaluate the quality of the observational studies, and the Jadad score evaluated randomized controlled trials. Among the 1003 studies initially identified, five observational trials and one randomized controlled trial were eligible for inclusion. All studies included in the meta-analysis were considered high quality. Risk for any type of fracture was higher in the surgical group than in the non-surgical group (risk ratio [RR] 1.29, 95% confidence interval [CI] 1.18-1.42). After surgery, the fracture risk in non-vertebral sites was significantly increased, especially in the upper limbs (RR 1.42, 95% CI 1.08-1.87; and RR 1.68, 95% CI 1.15-2.45). Compared with those with restrictive procedures, subjects who underwent mixed restrictive and malabsorptive procedures tended to have an increased fracture risk (RR 1.54, 95% CI 0.96-2.46). To conclude, bariatric surgery is associated with an increased risk of total and non-vertebral fractures, especially in the upper limbs.

The application of transcatheter angiographic embolization (TAE) is controversial in the treatment of ulcer bleeding. This study aims to determine rebleeding risk factors and evaluate the efficacy of prophylactic TAE (p-TAE) following endoscopic hemostasis in rebleeding prevention of Forrest lla ulcers. The medical records of Forrest lla ulcer patients who underwent endoscopic hemostasis (E group) and endoscopic hemostasis plus p-TAE (E + p-TAE group) in West China Hospital from May 2009 to May 2018 were retrospectively reviewed. Baseline characteristics, clinical efficacy, and rebleeding risk factors were analyzed. As a result, a total of 102 patients were included, with 75 and 27 patients in E and E + p-TAE group, respectively. Most of the baseline data in E and E + p-TAE group were similar except for the proportion of protruded non-bleeding visible vessel (NBVV) (E group vs E + p-TAE group, 50.7% vs 74.1%, P = .035). The rebleeding rate of E + p-TAE group (3.7%) was significantly lower than E group (24.0%) (P = .02). The protruded NBVV (OR: 6.896, 95% confidence interval [CI]: 1.532–30.642, P = .01) and employment of p-TAE (OR: 0.038, 95% CI: 0.003–0.448, P = .009) were identified as independent risk factors for Forrest IIa ulcer rebleeding. Additionally, log-rank test indicated the rebleeding occurrence was greatly reduced by p-TAE in patients with protruded NBVVs (P = .006). In conclusion, the protruded NBVV and employment of p-TAE were the independent risk factors tightly associated with rebleeding of Forrest IIa ulcer. P-TAE following endoscopic hemostasis could effectively prevent Forrest IIa ulcer from rebleeding.

Introduction During the coronavirus disease 2019 (COVID-19) pandemic, endoscopists have high risks of exposure to exhaled air from patients during gastroscopy. To minimize this risk, we transformed the oxygen mask into a fully closed negative-pressure gastroscope isolation mask. This study aimed to evaluate the effectiveness, safety, and feasibility of use of this mask during gastroscopy. Methods From February 28, 2020, to March 10, 2020, 320 patients undergoing gastroscopy were randomly assigned into the mask group (n = 160) or conventional group (n = 160). Patients in the mask group wore the isolation mask during gastroscopy, whereas patients in the conventional group did not wear the mask. The adenosine triphosphate fluorescence and carbon dioxide (CO2) concentration in patients' exhaled air were measured to reflect the degree of environmental pollution by exhaled air. Patients' vital signs, operation time, and adverse events during endoscopy were also evaluated. Results Four patients were excluded because of noncooperation or incomplete data. A total of 316 patients were included in the final analysis. The difference between the highest CO2 concentration around patients' mouth and CO2 concentration in the environment was significantly decreased in the mask group compared with the conventional group. There was no significant difference in the adenosine triphosphate fluorescence, vital signs, and operation time between the 2 groups. No severe adverse events related to the isolation mask, endoscopy failure, or new coronavirus infection during follow-up were recorded. Discussion This new isolation mask showed excellent feasibility of use and safety compared with routine gastroscopy during the COVID-19 pandemic.

Yuefeng Li,1,2,* Xiaofen Zhou,2,* Qiongying Zhang,3 Endong Chen,2 Yihan Sun,2 Danrong Ye,2 Ouchen Wang,2 Xiaohua Zhang,2 Jianxin Lyu1 1Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Pathology Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China *These authors contributed equally to this work Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial–mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future. Keywords: papillary thyroid carcinoma, hypoxia, metastasis, epithelial–mesenchymal transition

Supplemental Digital Content is available in the text, The worldwide prevalence and incidence of diabetes and obesity are increasing in pandemic proportions. Thus, regular health examination is an important way for early detection of diabetes and glucose intolerance. The present study aims to detect the blood glucose distribution characteristics of the participants in the Health Examination Center at West China Hospital, Sichuan University from 2010 to 2016. A prospective cohort included 9168 Chinese participants, aged 18 years or more, who had available information on fasting blood glucose concentrations at the start of the study (2010). Examination surveys were conducted every year from 2010 to 2016. Cases having serum level of fasting blood glucose between 2.2 and 6.1 mmol/L were considered as normality, while serum level of fasting blood glucose < 2.2 or higher than 6.2 mmol/L were considered as abnormality. The percentage of participants having normal level of glucose was gradually reduced both in males and females from 2010 to 2016, by which the percentage of males having normal level of glucose was significantly lower than that in females. Moreover, the mean level of glucose was significantly increased from 2010 to 2016 both in males and females overall, and the mean level of glucose was higher in males compared with that in females every year. Furthermore, we showed that the level of glucose was gradually increased year by year in each age group, and the level of glucose was higher in aged cases compared with the young population. The study population in the current study showed higher levels of glucose with ages increasing, and males indicated higher expression of glucose than that in females. Some preventive action may be adopted early and more attention can be paid to this health-examination population.

Based on the function of high performance DSP analog-digital converter (ADC) and pulse width modulator (PWM), a general digital PID control Buck converter is designed. Based on design of main circuit, the basic principle of PID control algorithm based on PWM is discussed in detail. Through the analysis of the PWM generation mode by DSP and PID control algorithm, a universal digital PID controller is designed. Then a prototype of digital control Buck converter based on PWM is constructed. On one hand, static tests showed that static value of the output voltage changes very little in the presence of input voltage and load change of Buck converter. On the other hand, dynamic tests showed that its output voltage fluctuation peak is small when Buck converter input voltage and load fast changes, and can recover quickly. Experiments showed that the proposed system is high accuracy, fast dynamic response and robustness.

To report a case of endoscopic enucleation of a gastrointestinal stromal tumor of the ampulla of Vater. The tumor resection was performed by needle knife endoscopic submucosal dissection. The tumor was resected completely without serious complications and the patient recovered rapidly. Endoscopic enucleation may be an alternative treatment for gastrointestinal stromal tumors of the ampulla of Vater for patients who fulfill certain requirements.

Neuroendocrine tumors (NETs) of the main duodenal papilla are rare. Surgery such as pancreaticoduodenectomy is traditionally recommended as the standard treatment for papillary neuroendocrine tumors. Endoscopic resection is increasingly used for treating these lesions. However, resection of papillary NETs using endoscopic submucosal dissection (ESD) technique was scarcely reported. In this paper, we report a patient with neuroendocrine tumor of the main duodenal papilla originating from the muscularis propria on EUS underwent successful endoscopic submucosal dissection using a duodenoscope. With 6-month followed up, no stenosis of bile and pancreatic ducts or relapse of tumor occurred.

i o j a f t A e e g v i t t h Esophageal leiomyomas are the most common benign mesenchymal tumors of the esophagus. Giant esophageal leiomyomas usually originate from the muscularis propria and are located in the lower esophagus.1,2 Surgical resecion remains the main therapeutic option for symptomatic nd complicated patients. With the progression of thoraoscopic and GI endoscopic therapy, multiple choices for esection of esophageal leiomyoma have become feasile.3,4 Although some investigators consider a large leiomyoma arising from the muscularis propria to be a contraindication to endoscopic removal, we present here a small case series of 5 patients who underwent enucleation of esophageal leiomyomas using endoscopic techniques in our endoscopy center.