Background and Aims nsedated colonoscopy is often associated with patient discomfort and may increase procedural difficulty for endoscopists. This study aimed to investigate the influence of perianal lidocaine application on the comfort level of patients and endoscopic operations during unsedated colonoscopy. Methods 122 patients aged 18-40 years were enrolled and randomly allocated to colonoscopy with 2% lidocaine (experiment group, n = 61) or normal saline (control, n = 61) smeared around the anus. The primary outcomes were anal pain score and abdominal pain score during and after colonoscopy, assessed using a visual analogue scale (VAS). Secondary outcomes included cecal intubation time, polyp detection rate, adenoma detection rate, and adverse events. Results There was no statistical difference between groups in terms of abdominal pain scores during unsedated colonoscopy. Abdominal pain scores after colonoscopy were significantly lower in the lidocaine group than in the saline group. (P < 0.001). However, the lidocaine group had significantly lower anal pain scores during and after colonoscopy (P < 0.001) and a shorter cecal intubation time (P < 0.001). Polyp and adenoma detection rates were higher in the lidocaine group (P < 0.05). Junior endoscopists achieved greater improvements in these outcomes compared to senior endoscopists. Conclusion Perianal application of lidocaine may reduce anal pain and may improve procedural efficiency during unsedated colonoscopy, particularly among junior endoscopists.

Gastric cancer (GC) remains a significant global health burden due to its high incidence and mortality, especially in China. This study aimed to evaluate the performance of combined serological assessment of pepsinogen (PG) and Helicobacter pylori (H. pylori) antibodies for identifying gastric precancerous conditions. From November 2016 to September 2019, an observational cohort study was performed to evaluate serum levels of PG and H. pylori antibodies. Among 19,879 participants, four groups were defined based on serological status: Group A (PG–/ H. pylori–), Group B (PG–/ H. pylori+), Group C (PG+/ H. pylori+), and Group D (PG+/ H. pylori–). Participants from Groups C and D were included in the analysis, while individuals from Groups A and B were randomly selected at a 3:1 ratio relative to Groups D and C, respectively. In total, 1,152 subjects underwent endoscopic and histopathological assessment. Group C demonstrated significantly elevated odds of atrophic gastritis (AG) (OR = 1.98; 95

: As a non-essential element for plant growth and development, the heavy metal mercury (Hg) has significant toxicity to plants. The aim of this study was to investigate the effect of mercuric ion (Hg 2+ ) on the oxidant response and calcium ion (Ca 2+ ) in the protoplasts of Arabidopsis thaliana . The protoplast cells were exposed to 5.0, 10.0, and 20.0 mmol/L Hg 2+ for 0.5 and 1.0 h, respectively. To detect the effect of Hg 2+ on the Reactive Oxygen Species (ROS) with the laser scanning confocal microscopy, 2’ 7’-Dichlorofluorescent yellow Diacetate (DCFH-DA) was used to label ROS in protoplast cells of Arabidopsis thaliana . The result of confocal microscopy analysis showed that the level of ROS was increased in protoplast cells after the treatments of 5.0, 10.0, and 20.0 mmol/L Hg 2+ . However, the activity of antioxidant enzymes Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GSH-PX) in protoplasts was decreased by 5.0, 10.0, and 20.0 mmol/L Hg 2+ treatments. In addition, ion chromatography was used to study the effect of Hg 2+ on the content of Ca 2+ in the protoplasts of Arabidopsis thaliana . It showed that the content of Ca 2+ in the outer cell of protoplasts was increased after the treatments of 5.0, 10.0, and 20.0 mmol/L Hg 2+ . In conclusion, Hg 2+ decreases the activity of antioxidant enzymes and induces the elevation of ROS in the protoplast cells. Mercuric ion inhibits the absorption of Ca 2+ by protoplast cells and the change of Ca 2+ content may affect ROS level in the protoplasts of Arabidopsis thaliana .

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin–Eosin, Masson’s trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-β1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-β pathway was found to play an important role in its development.

As a common foreign body in children, magnet ingestion has been a widespread health issue. Unlike single magnet, ingestion of multiple magnets, especially those high-powered like Buckyballs could cause significant GI injury, e.g., perforation and fistula. Hereby we present a "push-and-pull" trick for management of a rare circumstance of Buckyballs ingestion.

Cinnamoyl-containing natural products (CCNPs) are a small class of bacterial metabolites with notable bioactivities. The biosynthesis of cinnamoyl moiety has been proposed to be assembled by an unusual highly reducing (HR) type II polyketide synthases (PKS). However, the biosynthetic route, especially the cyclization step for the benzene ring formation, remains unclear. In this work, we successfully reconstituted the pathway of cinnamoyl moiety in kitacinnamycin biosynthesis through a step-wise approach in vitro and demonstrated that a three-protein complex, Kcn17-Kcn18-Kcn19, can catalyze 6π-electrocyclization followed by dehydrogenation to form the benzene ring. We found that the three-protein homologues were widely distributed among 207 HR type II PKS biosynthetic gene clusters including five known CCNPs. In contrast, in the biosynthesis of youssoufene, a cinnamoyl-containing polyene, we identified that the benzene ring formation was accomplished by a distinct orphan protein. Thus, our work resolved the long-standing mystery in cinnamoyl biosynthesis and revealed two distinct enzymes that can synthesize benzene rings via polyene precursors.

Hepatocellular carcinoma (HCC) has constituted a significant health burden worldwide, and patients with advanced HCC, which is stage C as defined by the Barcelona Clinic Liver Cancer staging system, have a poor overall survival of 6-8 months. Studies have indicated the significant survival benefit of treatment based on sorafenib, lenvatinib, or atezolizumab-bevacizumab with reliable safety. In addition, the combination of two or more molecularly targeted therapies (first-plus second-line) has become a hot topic recently and is now being extensively investigated in patients with advanced HCC. In addition, a few biomarkers have been investigated and found to predict drug susceptibility and prognosis, which provides an opportunity to evaluate the clinical benefits of current therapies. In addition, many therapies other than tyrosine kinase inhibitors that might have additional survival benefits when combined with other therapeutic modalities, including immunotherapy, transarterial chemoembolization, radiofrequency ablation, hepatectomy, and chemotherapy, have also been examined. This review provides an overview on the current understanding of disease management and summarizes current challenges with and future perspectives on advanced HCC.

Background Esophageal cancer is associated with high incidence and mortality worldwide. Differential expression genes (DEGs) and weighted gene co-expression network analysis (WGCNA) are important methods to screen the core genes as bioinformatics methods. Methods The DEGs and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the hub module in the WGCNA. The CCNB1 was identified as the hub gene based on the intersection between DEGs and the greenyellow module in WGCNA. Expression levels and prognostic values of CCNB1 were verified in UALCAN, GEPIA2, HCMDB, Kaplan–Meier plotter, and TIMER databases. Results We identified 1,044 DEGs from dataset GSE20347, 1,904 from GSE29001, and 2,722 from GSE111044, and 32 modules were revealed by WGCNA. The greenyellow module was identified as the hub module in the WGCNA. CCNB1 gene was identified as the hub gene, which was upregulated in tumour tissues. Moreover, esophageal cancer patients with higher expression of CCNB1 showed a worse prognosis. However, CCNB1 ‘might not play an important role in immune cell infiltration. Conclusions Based on DEGs and key modules related to esophageal cancer, CCNB1 was identified as the hub gene, which offered novel insights into the development and treatment of esophageal cancer.

We congratulate Maehata et al1Maehata T. Fujimoto A. Uraoka T. et al.Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissection.Gastrointest Endosc. 2020; 92: 667-674Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar on their study. The authors reported that dual red imaging (DRI) can facilitate hemostasis during endoscopic submucosal dissection (ESD) because of improved visualization of the bleeding point, compared with white-light imaging (WLI). Although it is a great study, we would like to share our reservations and suggestions for further research. First, the authors mentioned that if subsequent bleeding was detected after the use of WLI, the endoscopist switched to DRI immediately, based on the discretion of the endoscopist. Then, the hemostasis times between the WLI and DRI groups were analyzed. However, it is worth noting that the initial hemostasis with WLI may affect the subsequent hemostasis time with DRI. For example, when partial microvascular bleeding has been stopped in WLI, while bleeding is still continuing because of some potential factors, the endoscopist may switch to DRI to observe the last bleeding points and stop the bleeding. However, we could not draw a conclusion that hemostasis time in DRI is shorter without a direct comparison to attempts at bleeding control with WLI only. Second, a very interesting approach–measuring distances of eye movement–was used to illustrate the advantages of DRI. We strongly agree with this approach. However, the distance from the eye to the video, the number of head turns, and the experience of endoscopists involved are also factors that may affect the distances of eye movement and should have been controlled for. Finally, the authors mentioned that DRI may have a stress-reducing effect on both the ability to identify bleeding points earlier and the color. We support this hypothesis,2Fujimoto A. Saito Y. Abe S. et al.Haemostasis treatment using dual red imaging during endoscopic submucosal dissection: a multicentre, open-label, randomised controlled trial.BMJ Open Gastroenterol. 2019; 6e000275Crossref PubMed Scopus (3) Google Scholar but the author could have reached a more convincing conclusion by the questionnaire. We thank the authors and encourage similar efforts to advance the clinical benefit of ESD. All authors disclosed no financial relationships. Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissectionGastrointestinal EndoscopyVol. 92Issue 3PreviewHemostasis during endoscopic submucosal dissection (ESD) can sometimes be challenging and stressful for the endoscopist. Therefore, we aimed to assess the usefulness of dual red imaging (DRI), a new image enhancement technique that uses 3 wavelengths (540, 600, and 630 nm) to visualize bleeding points and to examine the efficacy of DRI in shortening the time required to achieve hemostasis (hemostasis time) during ESD. Full-Text PDF

Cancer is one of the serious diseases that endanger human health and bring a heavy burden to world economic development. Although the current targeted therapy and immunotherapy have achieved initial results, the emergence of drug resistance shows that the existing research is far from enough. In recent years, the tumor microenvironment has been found to be an important condition for tumor development and has profound research value. The SLC16 family is a group of monocarboxylic acid transporters involved in cancer metabolism and the formation of the tumor microenvironment. However, there have been no generalized cancer studies in the SLC16 family. In this study, we conducted a pan-cancer analysis of the SLC16 family. The results showed that multiple members of the SLC16 family could be used as prognostic indicators for many tumors, and were associated with immune invasion and tumor stem cells. Therefore, the SLC16 family has extensive exploration value in the future.

LASS2 is a novel tumor‐suppressor gene and has been characterized as a ceramide synthase, which synthesizes very‐long acyl chain ceramides. However, LASS2 function and pathway‐related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes β‐catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin–proteasome pathway, phosphorylation of LASS2 is essential for β‐catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Furthermore, we find that dephosphorylation of LASS2 at serine residue 248 significantly enhances prostate cancer cell growth and metastasis in vivo, indicating that phosphorylated LASS2 inhibits prostate carcinogenesis through negative regulation of Wnt/β‐catenin signaling. Thus, our findings implicate LASS2 as a potential biomarker and therapeutic target of prostate cancer.

The goal of this systematic review was to compare the clear liquid diet and the low-residue diet to determine which is better for bowel preparation before colonoscopy. A literature search for randomized controlled trials on the effects of employing the clear liquid diet and low-residue diets before colonoscopy was conducted in major online English databases (PubMed, Web of Science, and Ovid EMBASE). After the systematic review of all 16 studies, the outcomes including quality of bowel preparation, tolerance, willingness to repeat, and adverse effects were analyzed through meta-analysis. The statistical analysis was performed by using RevMan 5.3 software. No statistically significant difference was observed between the low-residue diet and clear liquid diet groups (odds ratio [95% confidence interval] = 1.19 [0.79, 1.81]; p = .41). There was no statistically significant difference between the Boston Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.21, −0.14]; p = .68) Ottawa Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.19, 0.11]; p = .59) scores of the two groups. The quality indicators for colonoscopy of the two groups were not statistically significant. However, patient tolerance to the low-residue diet was higher (odds ratio [95% confidence interval] = 1.86 [1.47, 2.36]; p < .01). More patients in the low-residue diet group were willing to repeat the low-residue diet for bowel preparation (odds ratio [95% confidence interval] = 2.34 [1.72, 3.17]; p < .01). More patients in the clear liquid diet group experienced hunger, nausea, and vomiting. People who employed the low-residue diet before colonoscopy had the same quality of bowel preparation as those with clear liquid diet. Meanwhile, the tolerance of people with low-residue diet was better than people with clear liquid diet, and these people were more willing to repeat the colonoscopy with less adverse events.

The immune system recognizes and attacks non-self antigens, making up the cornerstone of immunity activity against infection. However, during organ transplantation, the immune system also attacks transplanted organs and leads to immune rejection and transplantation failure. Interestingly, although the embryo and placenta are semi-allografts, like transplanted organs, they can induce maternal tolerance and be free of a vigorous immune response. Also, embryo or placenta-related antibodies might adversely affect subsequent organ transplantation despite the immune tolerance during pregnancy. Therefore, the balance between the immune tolerance in maternal-fetal interface and normal infection defense provides a possible desensitization and tolerance strategy to improve transplantation outcomes. A few studies on mechanisms and clinical applications have been performed to explore the relationship between maternal-fetal immune tolerance and organ transplantation. However, up to now, the mechanisms underlying maternal-fetal immune tolerance remain vague. In this review, we provide an overview on the current understanding of immune tolerance mechanisms underlying the maternal-fetal interface, summarize the interconnection between immune tolerance and organ transplantation, and describe the adverse effect of pregnancy alloimmunization on organ transplantation.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA-34a (miR-34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR-34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle-related genes (cyclin D1, PCNA, and p21) and inhibited the proliferation of prostate cancer cells. Furthermore, we found that curcumin significantly upregulated the expression of miR-34a, along with the downregulated expression of β-catenin and c-myc in three prostate cancer cell lines. Inhibition of miR-34a activated β-catenin/c-myc axis, altered cell cycle-related genes expression and significantly suppressed the antiproliferation effect of curcumin in prostate cancer cells. Findings from this study revealed that miR-34a plays an important role in the antiproliferation effect of curcumin in prostate cancer.

Prostate cancer is the most common malignancy in men. Phthalate esters are a class of environmental endocrine disruptors and were reported to be cancer promoting agents, however the potential role of phthalate esters in prostate cancer has been rarely reported. Mounting evidence has shown that miR-34a is a master tumor suppressor miRNA in cancer. The aim of this study was to investigate the role of butyl benzyl phthalate (BBP), one of the typical phthalate esters, in cell proliferation of prostate cancer cells. Human prostate cancer LNCaP and PC-3 cells were exposed to low dose of BBP for 6 days. The results showed that 10(-6) and 10(-7) mol/L BBP increased the expression of cyclinD1 and PCNA, decreased p21 expression, and induced cell growth in both LNCaP and PC-3 cells. Furthermore, we found that BBP significantly downregulated the expression of miR-34a, along with upregulation of miR-34a target gene c-myc. Using cell tranfection of miR-34a mimic and inhibitor, we demonstrated that BBP promoted cell proliferation through miR-34a/c-myc axis in prostate cancer cells. Findings from this study could provide new insight into the involvement and the molecular mechanism of phthalate esters on prostate cancer.

Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. β‑carotene, a carotenoid present in fruits, vegetables and rice, suppresses cancer progression. In this investigation, we evaluated the regulatory role of Notch pathway in tobacco smoke‑mediated gastric EMT and the preventive effect of β‑carotene using a BALB/c mouse smoking model. Exposure of mice to tobacco smoke reduced levels of epithelial markers, while the expression of mesenchymal markers were increased. We further found that Notch pathway modulated tobacco smoke-triggered EMT in the stomach of mice, as evidenced by these findings that tobacco smoke activated Notch activities, and tobacco smoke induced EMT was reversed by blocking Notch activities with FLI‑06. Moreover, treatment of β‑carotene prevented tobacco smoke‑mediated activation of Notch and EMT changes. Our data suggested that Notch regulate tobacco smoke induced gastric EMT and the protective effects of β‑carotene in vivo. These findings may establish a new mechanism for tobacco smoke-associated gastric tumorigenesis and its chemoprevention.

Prostate cancer is one of the most commonly diagnosed cancers in man. Studies have shown that phthalates may act as promoters in various types of cancer; however, the role of phthalates in prostate cancer has been rarely reported. The MAPK/AP-1 pathway is a vital regulator of cell proliferation in cancer. In this report we found that three typical phthalates, diethylhexyl phthalate (DEHP), Butyl benzyl phthalate (BBP) and Dibutyl phthalate (DBP), up-regulated cyclinD1 and PCNA, down-regulated P21, inducing proliferation of prostate cancer cells. Furthermore, we found that phthalates increased the expression of p-ERK5 and p-p38, along with upregulation of AP-1 (p-c-fos and p-c-jun). In studies with ERK5 and a p38 inhibitor, our data showed that downregulation of p-ERK5 or p38 inhibited phthalate-triggered cell proliferation. Taken together, findings from this study suggest that phthalates activate MAPK/AP-1 pathway and may potentially promote cell proliferation in prostate cancer, thus providing new insight into the effects and the underlying mechanism of phthalates on prostate cancer.

Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3 cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1 year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.