Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

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.

Esophagofundostomy combined with pericardial devascularization for the treatment of esophagogastric variceal bleeding / 中华普通外科杂志

Objective:To investigate the clinical effect of esophagofundostomy combined with pericardial devascularization in the treatment of upper gastrointestinal hemorrhage caused by portal hypertension.Methods:The clinical data of 108 patients with portal hypertension admitted to the Affiliated Hospital of Inner Mongolia Medical University from Feb 2009 to Feb 2015 were analyzed. Among them 42 patients underwent esophagofundostomy combined with pericardial devascularization as the study group, and 66 patients underwent pericardial devascularization only as the control group. All patients presented with splenomegaly or hypersplenism; the spleen was routinely removed during the operation.Results:The difference of operation time between the study group and the control group was statistically significant [(157±41) min vs. (143±27) min, t=2.81, P<0.05]. The improvement in the esophagogastric varices in the study group within 6 months was significantly better than that in the control group( Z=2.47, P<0.05). In addition, the rebleeding rates of varicose veins within 1, 3 and 5 years in the study group was 2%, 5% and 10%, while that in the control group was 15%, 21% and 26% (χ 2=5.49, 4.27, 4.31, all P<0.05). Conclusions:Esophagofundostomy combined with pericardia devascularization achieves complete devascularization and low rebleeding rate.

Surgical treatment of primary retroperitoneal tumor: report of 42 cases / 中国普通外科杂志

ObjectiveTo study the diagnosis and treatment of primary retroperitoneal tumor ( PRT) and the key for preventing and treating of recurrent retroperitoneal tumor (PRT).MethodsThe clinical data of 42 patients with PRT operated on from 1990 to 2000 were retrospectively analyzed.ResultTumors were benign in 19 patients and malignant in 23. Of the 19 patients with benign tumor, 15 underwent complete resection with incidental organ resection in 3 cases, palliative resection in 1 case, and complete resection of recurrent tumor in one. Of the 23 malignant tumors, complete resection was performed in 9 cases, complete resection with incidental organs resection in 11 cases, biopsy only in 3 cases. There was no operative death.ConclusionPreoperative imaging results are gists on which the resectability is judged, and complete resection is the only hope of cure. Surgical resection is the therapy of choice for postoperative recurrent PRT.

The causes and the management of postsplenectomy fever in portal hypertensive patients / 中国普通外科杂志

ObjectiveTo investigate the causes and management of postsplenectomy continuous fever in portal hypertensive patients. MethodThe clinical data of 329 portal hypertension patients with liver cirrhosis undergoing splenectomy from 1992 to 2001 were reviewed. Among those, 72 patients suffered from a fever higher than 38.5℃ for more than 2 weeks postoperatively. ResultThe most common cause was portal or splenic vein thrombosis and hematocele or hydrops and infection in splenic recess. Portal or splenic vein thrombosis was related to the surgical modality adopted and liver function. ConclusionPortal system thrombosis and hematocele, hydrops, or infection in the splenic recess were among the most common causes leading to postoperative long-term fever in these patients. Active anticoagulant use, effective drainage, antibiotic therapy and judicious application of surgical modality will help to reduce the rate of postoperative fever.