Endoscopic ultrasonography (EUS)is routinely performed before endoscopic submucosal dissection (ESD)for treatment of upper gastrointestinal stromal tumors.However,when a miniprobe sonography (12,15 and 20 MHz)was used,the size of tumor revealed by EUS was often inconsistent with what it actually was,which might increase the difficulty of ESD and the risk of perforation and massive bleeding.Aims:To investigate the value of standard probe (5 and 7.5 MHz)EUS in detecting the size of upper gastrointestinal stromal tumors before ESD.Methods:Clinical data of patients who were suspicious of esophageal and gastric stromal tumors by gastroscopy and EUS from Jan.2012 to Oct.2014 at the Renmin Hospital of Wuhan University were collected.Of them,195 cases treated by ESD were retrospectively analyzed.Results:Of 195 cases treated by ESD,37 cases diagnosed by standard probe EUS and 108 cases diagnosed by miniprobe EUS were confirmed as stromal tumors by pathology.Fourteen cases were failure for ESD and then transferred to surgical treatment,one was due to misjudgement of the origin of tumor by standard probe EUS and 9 were due to misjudgement of the size of tumor by miniprobe EUS.The misjudgement rate of standard probe EUS was lower than that of miniprobe EUS with an insignificant difference (2.7%vs.8.3%,P>0.05).In 9 cases misjudged by miniprobe EUS, the size of tumor presented by miniprobe EUS was significantly smaller than its real size [(1.22 ±0.51)cm vs.(3.97 ±1.06)cm,P<0.01].ESD was avoided or terminated in 3 cases because of the accurate estimation of tumor origin, structure and blood flow by standard probe EUS.Conclusions:For patients who are going to receive ESD for suspected upper gastrointestinal stromal tumors,it would be best to select standard probe EUS to detect the size,origin and blood flow of the tumor before ESD.It will decrease the risk and improve the success rate of ESD.

Objectives To evaluate the application of preoperative endoscopic ultrasonography ( EUS) in assessment of invasive risk and selection of therapeutic modalities for gastric stromal tumors ( GST).Methods The clinical data of 135 patients with GST admitted in our hospital from January 2011 to January 2012 were retrospectively analyzed.The invasion extent of GST was assessed by image of EUS before surgery, and compared with pathological results after surgery; the Fletcher 4-tier system was used for predicting the aggressiveness of GST.The selection of therapeutic modalities in 38 patients, who underwent surgical treatment was analyzed.Results No specific clinical manifestations were noticed , but some patients with enormous GST had symptoms of ulcer , hematemesis , and melena.Among 135 patients 97 cases received conservative treatment and followed up;in remaining 38 cases, according to invasion risk assessed by EUS, there were 9 cases in low risk, 18 in intermediate risk and 11 in high risk.The surgical modalities were selected based on the risk assessment:endoscopic therapy was performed in 15 cases, laparoscopic with gastroscopic surgery in 17 cases and laparotomy in 6 cases.The coincidence rate of diagnosis between preoperative EUS and postoperative pathological examination was 79.0%.Conclusions Preoperative endoscopic ultrasonography is of value in assessment of invasion risk and selection of appropriate therapeutic modalities for gastric stromal tumors.

[ ABSTRACT] AIM: To investigate the influence of advanced glycosylation end products-modified bovine serum albumin (AGE-BSA) on mammalian target of rapamycin complex 1 (mTORC1), urokinase-type plasminogen activator re-ceptor ( uPAR) , and cell mobility in the podocytes, and to further explore the probable relationship.METHODS: The conditionally immortalized mouse podocyte cell line was cultured in vitro.MTT assay and immunofluorescence were used to analyze the cell viability and cytoskeleton of the podocytes treated with the stimuli and intervention agents.The activity of mTORC1 and the expression level of uPAR in normal podocytes and podocytes treated with control BSA or AGE-BSA were detected by Western blotting.The migration ability of the podocytes was determined by would-healing assay.Rapamycin was added to inhibit the activity of mTORC1 along with the addition of AGE-BSA to observe the changes of uPAR and the motility of podocytes.RESULTS:No significant difference of the cell viability or cytoskeleton in the podocytes treated with the stimuli and intervention agents was observed.AGE-BSA up-regulated the activity of mTORC1 and the expression of uPAR, and induced the high mobility of the podocytes.Rapamycin obviously reduced the high expression level of uPAR and the increase in the migration ability of podocytes caused by AGE-BSA treatment.CONCLUSION: AGE-BSA might cause the high migration of podocytes through the mTORC1/uPAR signaling pathway.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.