Endoscopic retrograde appendicitis therapy (ERAT) vs appendectomy for acute uncomplicated appendicitis: A prospective multicenter randomized clinical trial.

OBJECTIVE: To compare the efficacy and feasibility of endoscopic retrograde appendicitis therapy (ERAT) with appendectomy for treating acute uncomplicated appendicitis. METHODS: This was a prospective multicenter randomized trial in which consecutive patients were randomized at a ratio of 1:1 to receive either ERAT or appendectomy. The outcomes included technical success rate, procedure time, postoperative pain relief, postoperative analgesic use, time to soft diet intake, length of postoperative hospital stay, postoperative complications, and recurrence rate. RESULTS: From August 2013 to December 2015, 110 patients with acute uncomplicated appendicitis were randomized to ERAT or appendectomy. The technical success rate was 94.55% for ERAT compared with 100% for appendectomy. Recurrence of appendicitis within 3-year follow-up occurred in 8 patients following ERAT. Postoperative abdominal pain was less frequent with ERAT than with appendectomy (21.15% [11/52] vs 87.27% [48/55], P < 0.001). Soft diet intake begun earlier after ERAT than appendectomy (6 h vs 48 h, P < 0.001), and post-procedure hospital stay was shorter (3 days vs 5 days, P < 0.001), as was the use of analgesics postoperatively (9.09% vs 49.09%, P < 0.001). CONCLUSIONS: ERAT is a feasible, safe, and effective alternative approach for the management of acute uncomplicated appendicitis. Compared with appendectomy, advantages of ERAT include no skin wound, organ preservation, reduced postoperative pain, early food intake, quick recovery, fewer postoperative complications, and shorter post-procedure hospitalization. The unsolved problem related to ERAT is the recurrence of appendicitis.

Individualized endoscopic management strategy for impacting jujube pits in the upper gastrointestinal tract: a 3-year single-center experience in northern China.

BACKGROUND: Impaction of jujube pits in the upper gastrointestinal (GI) tract is a special clinical condition in the northern Chinese population. Endoscopic removal is the preferred therapy, but there is no consensus on the management strategies. We reported our individualized endoscopic strategies on the jujube pits impacted in the upper GI tract. METHODS: In this retrospective study, we included 191 patients (male: 57; female: 134) who presented to our hospital with ingestion of jujube pits between January 2015 and December 2017. Demographic information, times of hospital visiting, locations of jujube pits, endoscopic procedures, post-extraction endoscopic characteristics were analyzed. Management strategies including sufficient suction, repeated irrigation, jejunal nutrition and gastrointestinal decompression were given based on post-extraction endoscopic characteristics and impacted locations. RESULTS: Peak incidence was in the second quarter of each year (85/191 cases, 44.5%). Among the 191 cases, 169 (88.5%) showed pits impaction in the esophagus, 20 (10.5%) in the prepyloric region and 2 (1.0%) in the duodenal bulb. A total of 185 patients (96.9%) had pits removed with alligator jaw forceps, and 6 (3.1%) underwent suction removal with transparent caps placed over the end of the endoscope to prevent injury on removal of these pits with two sharp painted edges. Post-extraction endoscopic manifestations included mucosal erosion (26.7%), mucosa laceration (24.6%), ulceration with a white coating (18.9%) and penetrating trauma with pus cavity formation (29.8%). All patients received individualized endoscopic and subsequent management strategies and showed good outcomes. CONCLUSIONS: Individualized endoscopic management for impacted jujube pits in the upper GI tract based on post-extraction endoscopic characteristics and impacted locations was safe, effective, and minimally invasive.

Risks of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis and Hyperamylasemia After Endoscopic Papillary Balloon Dilation: A Retrospective Analysis.

It is currently unclear whether endoscopic papillary balloon dilation (EPBD) is associated with increased severe postendoscopic retrograde cholangiopancreatography pancreatitis (PEP)-related morbidity owing to conflicting reports. This study aimed to investigate whether EPBD increases the risk of PEP and hyperamylasemia. Clinical data of patients with choledocholithiasis, treated at the Second Affiliated Hospital of Harbin Medical University from January 2015 to December 2016 were analyzed. Patients were divided into the EPBD group and endoscopic sphincterotomy (EST)+EPBD group, and their characteristics and PEP and hyperamylasemia incidences were compared. Incidences related to dilated balloon diameter were also analyzed. There were no significant differences in patient characteristics and the incidences of PEP (2.6% vs. 0%; P=0.257) and hyperamylasemia (4.4% vs. 5.6%; P=0.954) between the 2 groups. Results were similar even with different balloon dilatations. EPBD without endoscopic sphincterotomy did not increase the risk of PEP and hyperamylasemia. It is a safe option for choledocholithiasis patients.

Esophageal insufflation computed tomography for the diagnosis and management of esophageal submucosal tumors.

BACKGROUND: The selection of therapy for benign esophageal lesions depends in part on whether the lesion extends to or through the esophageal muscle wall. The advent of endoscopic dissection of deep lesions has made this distinction important in the choice between different forms of advanced endoscopic therapy. The goal of this study was to evaluate esophageal insufflation computed tomography (EICT) for the diagnosis and management of esophageal submucosal tumors (SMTs). METHODS: Between April 2011 and May 2013 at the Second Affiliated Hospital of Harbin Medical University, 27 patients with esophageal SMTs diagnosed by gastroscopy were studied observationally. Entry criteria included tumors larger than 0.5 cm. We compared endoscopic ultrasound (EUS) and EICT to assess lesion depth and the relationship between the submucosal lesion and the esophageal wall using the resected lesion as the gold standard. RESULTS: Twenty-seven esophageal SMTs were evaluated. EUS and EICT accurately identified nine as superficial to the muscularis propria. EICT correctly identified the relation of the tumor extension and the outer esophageal wall in all 18 lesions that originated from the muscularis propria; only nine were correctly assessed by EUS (P < 0.001). CONCLUSIONS: EICT enables improved judgment of the relation of esophageal lesions and the esophageal-mediastinal border. We propose EICT as a new, safe, effective, useful, simple and high-tolerance method for assessing the depth and relationships of esophageal submucosal lesions.

Submucosal Tunneling Endoscopic Resection (STER) and Other Novel Applications of Submucosal Tunneling in Humans.

The submucosal tunneling technique was originally developed to provide safe access to the peritoneal cavity for natural orifice transluminal endoscopic surgery procedures. With this technique, the submucosal tunnel becomes the working space for partial myotomy and tumor resection. The submucosal space has come to represent the "third space" distinguished from gastrointestinal lumen (first space) and peritoneal cavity (second space). New applications continue to be developed and further clinical applications in the future are anticipated. This article summarizes the current applications of submucosal tunneling endoscopic resection for subepithelial tumors and describes other related uses of submucosal tunneling.

In vivo cancer targeting and fluorescence-CT dual-mode imaging with nanoprobes based on silver sulfide quantum dots and iodinated oil.

In this article, a fluorescence-CT dual-mode nanoprobe is successfully synthesized by making use of distearoylphosphatidylethanolamine-poly(ethylene glycol)-folate (DSPE-PEG2000-FA) and other amphiphilic molecules to coat silver sulfide (Ag2S) quantum dots (QDs) and iodinated oil simultaneously. In vitro experiments show that the fluorescence wavelength of the nanoprobe is 1170 nm in the near infrared-II region. Its size is 139.6 nm, it has good dispersibility, and it has low cellular toxicity at concentrations up to 25 µg mL(-1) Ag. In vivo experiments revealed that the probe has a rather long circulation time (blood half-life of 5.7 hours), and the tissue histopathological tests show that it is not obviously harmful to major organs' normal function. Biochemical analysis (glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels) and blood analysis (white blood cell, red blood cell, hemoglobin and blood platelet counts) reveal that it has little influence on blood within 15 days of administration. When injected into HeLa xenograft nude mice by the tail vein, the probe elicited intensely enhanced fluorescence and X-ray computed tomography (CT) signals in the tumors after 24 hours, and the structure, size and position of tumor tissue were shown clearly. In a word, the probe has good tumor targeting capabilities, and it has significant value in fluorescence-CT dual-mode imaging in vivo.

An engineered coiled-coil polypeptide assembled onto quantum dots for targeted cell imaging.

Quantum dot (QD)-polypeptide probes have been developed through the specific metal-affinity interaction between polypeptides appended with N-terminal polyhistidine sequences and CdSe/ZnS core-shell QDs. The size and charge of a QD-polypeptide can be tuned by using different coiled-coil polypeptides. Compared to glutathione-capped QDs (QD-GSH), QD-polypeptide probes showed an approximately two- to three-fold luminescence increase, and the luminescence increase was not obviously related to the charge of the polypeptide. QD-polypeptide probes with different charge have a great effect on nonspecific cellular uptake. QD-polypeptide probes with negative charge exhibited lower nonspecific cellular uptake in comparison to the QD-GSH, while positively charged QD-polypeptide probes presented higher cellular uptake than the QD-GSH. A targeted QD-ARGD probe can obviously increase targeted cellular uptake in α v ß 3 overexpressing HeLa cells compared to QD-A. In addition, QD-polypeptide probes showed lower in vitro cytotoxicity compared to the original QDs. These results demonstrate that these QD-polypeptide probes with high specific cellular uptake, high fluorescence intensity and low background noise are expected to have great potential applications in targeted cell imaging.

Esophago-Cardial-Gastric Tunneling Peritoneoscopy: In Vivo Dog Survival Study.

BACKGROUND: Diagnostic peritoneoscopy is typically performed by using a rigid laparoscope. Inspired by gastric submucosal tunneling for peritoneal natural orifice transluminal endoscopic surgery access and peroral endoscopic myotomy for the treatment of achalasia, we developed a novel esophago-cardial-gastric tunneling (ECGT) peritoneoscopy technique with a flexible endoscope. This study aims to evaluate its feasibility and safety. MATERIALS AND METHODS: The study comprised 10 Beagle dogs. A longitudinal mucosal incision was made on the esophageal wall, and a submucosal tunnel was created through the cardia into the stomach. An incision was made in the muscular layer of the stomach, and then the endoscope was advanced into the peritoneal cavity. Peritoneoscopy with the flexible endoscope was performed. After intraperitoneal exploration, the esophageal mucosal entry was closed with endoclips. All dogs resumed food intake 12 hours after the procedures. Diets, behavior, and body temperature of all of the dogs were observed. Endoscopic examinations were performed 4 weeks after the procedure, and then the animals were sacrificed for necropsy. RESULTS: The ECGT peritoneoscopy was successfully done in all dogs. Diets, behavior, and body temperature were normal in all dogs. The entry of the esophagus was healed well in 9 dogs; the mucosa of the entry was torn in 1 dog, but the submucosal tunnel was healed well at the cardia. Necropsy showed complete closure of the gastric serosal exit, and no intraperitoneal abscess was found. Histopathological examinations showed submucosal tunnels healed well. CONCLUSIONS: The ECGT peritoneoscopy is feasible and safe for peritoneal exploration. It should be a good choice for the clinical application of diagnostic peritoneoscopy.

Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4­induced fibrosis in mice.

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4­induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4­induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar­treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4­induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.

Facile Synthesis of Gold Nanospheres Modified by Positively Charged Mesoporous Silica, Loaded with Near-Infrared Fluorescent Dye, for in Vivo X-ray Computed Tomography and Fluorescence Dual Mode Imaging.

We developed a simple and efficient method to synthesize a novel probe for both computed tomography (CT) and fluorescence imaging. Gold nanospheres were coated with positively charged mesoporous silica (Au@mSiO2-TTA) using a one-pot method to cohydrolyze quaternary ammonium silane and tetraethyl orthosilicate. Subsequently, IR-783, a negatively charged and water-soluble near-infrared fluorescent dye, was electrostatically adsorbed into the silica shell. Transmission electron microscopy imaging, X-ray powder diffraction, and energy dispersive X-ray spectroscopy indicated that Au@mSiO2-TTA had a clear core-shell structure, was monodisperse, had a large surface area (530 m2/g), and had a uniform pore size (2.2 nm). The mesoporous structure could effectively load fluorescent dye. After loading, the zeta potential of the nanoparticle dropped from 48 mV to 30 mV, and after additional modification with polyvinylpyrrolidone, it further reduced to 6 mV. Probe fluorescence was stable over time, and the probe was an effective CT contrast agent and as a near-infrared fluorescent probe. The half-life of the probe in the blood was 1.5 h, and the probe was mainly distributed in the spleen and liver 4 h after injection. Tissue sections showed that major organs were normal and without visible morphological changes, 6 days post injection, indicating the biocompatibility of the probe.

Composite silica coated gold nanosphere and quantum dots nanoparticles for X-ray CT and fluorescence bimodal imaging.

In this study, silica coated Au nanospheres (Au@SiO2) were prepared by a reverse microemulsion method; subsequently, a layer of fluorescent quantum dots (QDs) were adsorbed onto it and then it was coated with silica again. After modifying with PVP, the composite silica coated gold nanosphere and quantum dots nanoparticle (Au@SiO2-QDs/SiO2-PVP) was obtained. This composite structure contained Au and QDs, and it could be used for contrast-enhanced X-ray CT imaging and fluorescence imaging. Characterization showed that the composite nanoparticle had good dispersity, a high fluorescence intensity and a good effect of X-ray absorption, and it was suitable for using as a bimodal imaging probe.

One-pot two-step synthesis of core-shell mesoporous silica-coated gold nanoparticles.

Gold nanoparticles coated with mesoporous silica (Au@mSiO2) have been prepared by a facile one-pot two-step method. The resultant Au@mSiO2 exhibit an ideal core-shell structure with uniform mSiO2 coverage and without any interfacial adhesive layer on the Au surface. Some new explanations on the role that CTAB plays in the synthesis of Au@mSiO2 are discussed.

Multifunctional quantum dot-polypeptide hybrid nanogel for targeted imaging and drug delivery.

A new type of multifunctional quantum dot (QD)-polypeptide hybrid nanogel with targeted imaging and drug delivery properties has been developed by metal-affinity driven self-assembly between artificial polypeptides and CdSe-ZnS core-shell QDs. On the surface of QDs, a tunable sandwich-like microstructure consisting of two hydrophobic layers and one hydrophilic layer between them was verified by capillary electrophoresis, transmission electron microscopy, and dynamic light scattering measurements. Hydrophobic and hydrophilic drugs can be simultaneously loaded in a QD-polypeptide nanogel. In vitro drug release of drug-loaded QD-polypeptide nanogels varies strongly with temperature, pH, and competitors. A drug-loaded QD-polypeptide nanogel with an arginine-glycine-aspartic acid (RGD) motif exhibited efficient receptor-mediated endocytosis in αvß3 overexpressing HeLa cells but not in the control MCF-7 cells as analyzed by confocal microscopy and flow cytometry. In contrast, non-targeted QD-polypeptide nanogels revealed minimal binding and uptake in HeLa cells. Compared with the original QDs, the QD-polypeptide nanogels showed lower in vitro cytotoxicity for both HeLa cells and NIH 3T3 cells. Furthermore, the cytotoxicity of the targeted QD-polypeptide nanogel was lower for normal NIH 3T3 cells than that for HeLa cancer cells. These results demonstrate that the integration of imaging and drug delivery functions in a single QD-polypeptide nanogel has the potential for application in cancer diagnosis, imaging, and therapy.

Directed self-assembly of polypeptide-engineered physical microgels for building porous cell-laden hydrogels.

A novel approach to build porous cell-laden hydrogels through the self-assembly of coiled-coil polypeptides on the surface of physical microgels was developed. Both the extracellular microenvironments of pores and physical microgels within assembled constructs could be tailored simultaneously by tuning the polypeptide and morphological features of microgels.

Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-ß1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-ß1 were measured by real-time PCR. Collagen I and transforming growth factor ß1 (TGF-ß1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-ß1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-ß1 mRNA. Expressions of Collagen-1 and TGF-ß1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Carcino-embryonic antigen detection based on fluorescence resonance energy transfer between quantum dots and graphene oxide.

The mixture of graphene oxide (GO) and aptamer labeled fluorophore is widely used in developing fluorescent sensors for the analysis of biomolecules, according to the light signal 'off-on' procedure. Moreover, the laser-induced fluorescence-coupled affinity probe capillary electrophoresis (APCE) technique has been broadly applied for the separation of micromolecules. Here, a strategy is proposed for analysis of content of carcino-embryonic antigen (CEA) based on the combination of GO and quantum dots labeling aptamer (QD-aptamer) by capillary electrophoresis (CE). The method has three advantages: (i) combined with CE, only few samples are required and efficiency of separation is high, (ii) fluorescent detection can be carried out after separation of GO and fluorescence probe combined with targets by CE, while fluorescence detection sensitivity had been greatly improved, and (iii) the issues of APCE, including the effect of excess fluorescence probe and maximizing separation between analytes, could be solved by introducing GO. It has been proved that QD-aptamer-CEA complex can completely dissociate from GO. Results show that the fluorescence intensity has a linear relationship with the concentration of CEA in the range from 0.257 to 12.9 ng/mL, and the limit of detection is approximately 5 pg/mL (S/N=3). The proposed method with high specificity has been applied for the accurate analysis of content of CEA in patient׳s serum.