Upper gastrointestinal (GI) hemorrhage is a common clinical emergency worldwide. Endoscopic hemostasis is the current first line treatment. Nevertheless, for patients with severe active bleeding and ...challenging anatomy, endoscopic management can be still difficult and usually requires a higher level of surgical expertise. A simple and effective method of endoscopic hemostasis is therefore in acute clinical demand. Herein a hemostatic hybrid hydrogel comprised of hyaluronic acid and polyethylene glycol stabilized by thiourea–catechol coupling and disulfide bonds is reported. The hybrid hydrogels exhibit enhanced mechanical properties, short gelation time, and good blood clotting ability compared with fibrin gels. The in vivo hemostatic efficacy is confirmed in a rat model of arterial bleeding, in which the rapid gelation of hybrid hydrogels after topical application effectively arrests blood loss with no rebleeding occurring during resuscitation when blood pressure approximately recovers to normal. A large animal study further demonstrates the efficacy of hybrid hydrogels to achieve endoscopic hemostasis against upper GI hemorrhage in pigs. Follow‐up observations show that the hybrid hydrogels can remain adherent at the bleeding wound for 48 h, indicating the sustained hemostatic function in vivo. Collectively, this work demonstrates a promising hemostatic hydrogel for endoscopic hemostasis in upper GI hemorrhage.
A hybrid adhesive hydrogel comprised of hyaluronic acid and polyethylene glycol stabilized by thiourea–catechol coupling and disulfide bond is developed for endoscopic hemostasis of acute upper gastrointestinal hemorrhage. The hydrogels show enhanced mechanical properties, short gelation time, and good blood clotting ability, showing rapid and sustained hemostatic effects for 48 h in live pigs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while ...providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.
Ferromagnetic particles (FMPs) have attracted a large amount of attention for tumor treatment in recent decades in the form of magnetic hyperthermia and thermoablation therapies. Previous research ...has commonly focused on the improvement of the specific loss power and the increase in the particle concentration to enhance the heating temperature during hyperthermia. Instead of magnetic hyperthermia with passive particles, here a feasible approach of using reconfigurable swarms of ferromagnetic colloidal particles is reported to realize enhanced local hyperthermia. The concentration of the particle swarm can be tuned up to 500% of the original particle concentration via reversible pattern transformation, i.e., shrinking and swelling. The FMP swarms with a controllable pattern size show their potential for directed energy delivery and offer a new strategy for realizing a highly localized heating effect using a low dose of the active FMPs.
A reconfigurable ferromagnetic colloidal swarm is developed for enhanced local hyperthermia. The simulation and experimental results indicate that the local heating effects and the spatial resolution of the hyperthermia process can be significantly improved by using a microrobotic swarm.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention ...in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired.
Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric ...cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Antitumor and antimetastatic effects of the medicinal herb Andrographis paniculata (AP) in esophageal cancer (EC) have been previously reported. In this study, we aimed to uncover the potential ...functional components and the underlying molecular mechanisms of AP in EC treatment using network pharmacology and experimental validation. Twenty‐two potential active AP compounds against EC were revealed, including the antitumor/antiinflammatory compounds panicolin, moslosooflavone, and deoxyandrographiside. Epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), RAC‐alpha serine/threonine‐protein kinase (AKT1), prostaglandin‐endoperoxide synthase 2 (PTGS2), chemokine (C‐X‐C motif) ligand 8 (CXCL8), phosphatidylinositol 4,5‐bisphosphate 3‐kinase subunit alpha (PIK3CA), and toll‐like receptor 4 (TLR4) were most highly ranked among the predicted targets of AP in EC treatment and may play important roles in the anti‐EC effects of AP. KEGG pathway analysis revealed the enrichment of multiple cancer‐related pathways and signaling pathways. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting validation showed that overnight treatment with 850.3 μg/ml of AP water extract significantly reduced the mRNA expressions of EGFR and AKT in human EC‐109 cells. The presence of panicolin and moslosooflavone in the AP water extract samples were confirmed using LC‐MS against reference standards. This study has comprehensively revealed for the first time the potential functional components of AP in EC and explored the underlying molecular mechanisms. Future studies should characterize the potential pharmacological properties of the other highly ranked yet understudied compounds in AP detected.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Patients with metastatic esophageal squamous cell carcinoma (ESCC) have a grave prognosis with limited life expectancy. Here, a phase II clinical trial was conducted to investigate the effect of ...Andrographis paniculata (AP) on the palliative care of patients with metastatic ESCC. Patients with metastatic or locally advanced ESCC deemed unfit for surgery, and who have already completed palliative chemotherapy or chemoradiotherapy or are not fit for these treatments, were recruited. These patients were prescribed AP concentrated granules for 4 months. They also received clinical and quality of life assessments for clinical response, as well as positron emission tomography–computed tomography at 3 and 6 months after AP treatment for the assessment of tumor volume. Furthermore, the change in gut microbiota composition after AP treatment was studied. From the results, among the 30 recruited patients, 10 completed the entire course of AP treatment, while 20 received partial AP treatment. Patients who completed the AP treatment achieved significantly longer overall survival periods with the maintenance of the quality of life during the survival period when compared to those who could not complete AP treatment. The treatment effect of AP also contributed to the shift of the overall structure of gut microbiota for ESCC patients towards those of healthy individuals. The significance of this study is the establishment of AP as a safe and effective palliative treatment for patients with squamous cell carcinoma of the esophagus. To the best of our knowledge, this is the first clinical trial of AP water extract in esophageal cancer patients demonstrating its new medicinal use.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Endoscopic submucosal tunneling has evolved to allow endoscopic resection of subepithelial tumors of gastrointestinal tract without full-thickness perforation. This study aimed to ...investigate safety and efficacy of submucosal tunnel resection for these tumors.
Method
Patients with subepithelial tumors (SET) located in esophagus, gastric cardia, lesser curvature, and antrum were recruited. The size of tumor was limited to < 40 mm. The procedures were performed under general anesthesia. A mucosal entrance was created 2 cm proximal to the SET after submucosal injection. Submucosal tunnel was then extended and the tumor was dissected and mobilized with intact overlying mucosa. After complete dissection, the tumors would be retrieved per orally and mucosal entrance closed by endoclips.
Results
From June 2012 to December 2016, 51 patients with subepithelial tumors received POET. 39 patients had SET in stomach, 11 located in esophagus, and 1 in duodenum. The mean operative time was 90.46 ± 46.49 min, while the mean size of the tumors was 20.71 ± 14.05 mm. The POET was converted to endoscopic full-thickness resection (EFTR) in three patients with gastric subepithelial tumors located at greater curvature. The overall complication rate was 4.0%, and there was no bleeding, mucosal dehiscence, or leakage. The time to resume diet was 1.7 days, while the average hospital stay was 3.2 ± 1.0 days. The mean follow-up period was 19 ± 16 months, and only 1 patient developed recurrence of leiomyoma.
Conclusion
Per oral endoscopic tumor resection is safe and effective treatment for esophageal and gastric SET located at cardia, lesser curvature, and antrum. Currently, POET for treatment of upper GI SET is limited by the size and location of the tumor.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ