Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms.

RAGE belongs to immunoglobulin superfamily and serves as a ligand for various immunoregulatory molecules including S100B that has been demonstrated important to T cell mediated autoimmune diseases. In this context, we hypothesized that RAGE could also impact B cell mediated, T cell-dependent autoimmune diseases. This was tested using myasthenia gravis (MG) animal model, EAMG. We show that expression of both RAGE and S100B are increased during EAMG and the interaction between RAGE and S100B affected the Th1/Th2/Th17/Treg cell equilibrium, up-regulate AChR-specific T cell proliferation. Furthermore, addition of S100B in vitro stimulated splenocyte activity linked to COX-2 up-regulation. NS-398, a selective COX-2 inhibitor, effectively diminished S100B mediated activity of AChR-specific antibody secreting splenocytes. These findings suggested that a reciprocal relationship between RAGE and S100B promoted the development of EAMG, highlighting the importance of understanding the mechanisms of EAMG disease as a means of developing new therapies for the treatment of MG.

Effect of a three-piece inflatable penile prosthesis combined with a phosphodiesterase-5 inhibitor on erectile dysfunction.

OBJECTIVE: To investigate the therapeutic effect of implanting a three-piece inflatable penile prosthesis (IPP) combined with the phosphodiesterase-5 inhibitor sildenafil in severe erectile dysfunction (ED) patients. METHODS: This randomized controlled study included 123 ED patients. Sixty-two patients received the IPP implantation and 61 patients received the IPP implantation and the phosphodiesterase-5 inhibitor sildenafil. Erectile function and sexual life quality were evaluated using the five-item International Index of Erectile Function (IIEF) and modified Sexual Life Quality Questionnaire-Quality of Life domain (mSLQQ-QoL), respectively. Serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1 levels were assessed. Kaplan-Meier curves were used to assess the overall IPP survival. RESULTS: Implantation of the three-piece IPP with sildenafil improved erectile function and sexual life quality, alleviated the inflammatory response, reduced the complication rate, and improved overall IPP survival. CONCLUSION: Implantation of the three-piece IPP combined with a phosphodiesterase-5 inhibitor significantly improved clinical outcomes and the prognosis in ED patients.

Wine consumption and colorectal cancer risk: a meta-analysis of observational studies.

There were inconsistent results with respect to the correlation between consumption of wine and the development of colorectal cancer (CRC). We carried out a meta-analysis to investigate this issue. We included observational studies on the aforementioned relationship according to a literature search of Embase and Pubmed from inception till 28 February 2017. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated using a random-effects model. A total of eight case-control and nine cohort studies were identified, involving 12 110 CRC cases. The study showed that wine drinking was not associated with any greater risk for CRC (SRR=0.99, 95% CI: 0.89-1.10; Pheterogeneity<0.001) compared with nondrinkers. The subgroup analyses indicated that null associations were observed in men and women for colon and rectal cancer. Neither light to moderate (<2 drinks/day; SRR=0.93, 95% CI: 0.80-1.08, I= 69.2%) nor heavy (≥2 drinks/day; SRR=1.00, 95% CI: 0.86-1.16, I= 39.9%) consumption of wine was associated statistically with CRC risk. This meta-analysis suggests that any wine consumption was not associated with the risk of CRC. Null associations were shown in men and women for colon and rectal cancer.

[Preliminary experience with endoscope-assisted transoral excision of the submandibular gland].

OBJECTIVE: To discuss the indications, risks and benefits of endoscope-assisted transoral approach to excise the submandibular gland. METHODS: A retrospective review of a series of 12 patients treated by endoscope-assisted transoral submandibular gland excision was carried out. Of the 12 patients, 8 were chronic sialoadenitis (2 cases with sialolith), 3 were pleomorphic adenoma, and 1 was cyst of submandibular gland. Preoperatively, all patients were diagnosed as benign diseases by Ultrasonography, CT or MRI. Pathologic diagnosis of 8 cases were identified by fine needle aspiration cytology (FNAC) or fine needle aspiration biopsy (FNAB). RESULTS: Temporary lingual sensory paresis and temporary limitation of tongue movement were found in two patients. However, these signs soon resolved spontaneously within 1 - 3 months. There were no other complications. Postoperatively, mean satisfaction score with cosmetic results was 10. All patients were satisfied with the cosmetic results. No recurrences were found in patients with pleomorphic adenoma with a follow-up period ranged from 12 months to 48 months (median follow-up period: 36 months). CONCLUSIONS: Endoscope-assisted transoral excision of the submandibular gland is a feasible and safe approach for the benign diseases of the submandibular gland. The major advantages of this approach are no external scar and no injury to the marginal mandibular nerve.

[Selective neck dissection for treating recurrent branchial anomalies].

OBJECTIVE: To evaluate the role of selective neck dissection in the treatment of recurrent branchial anomalies. METHOD: The clinical data of 18 patients with recurrent branchial anomalies were retrospectively analyzed. In accordance with the embryologic and anatomic features of branchial anomalies, different types of selective neck dissection were applied. With dissection and protection of important vessels, nerves and other structures, enbloc resection principles were applied to extirpate branchial lesions, scarrings and inflammatory granuloma during the operation. RESULT: Of all 18 patients, 16 cases were healed with primary healing, 2 cases with local incision infection were healed after dressing changes. A temporary facial nerve paralysis occurred in 1 case with recurrent first branchial cleft fistula postoperatively, and completely recovered 2 months after operation. A postoperative temporary vocal cord paralysis occurred in 1 case with recurrent fourth branchial cleft fistula, and totally recuperated 1 month after operation. No recurrences were found in all 18 cases with a follow-up period of 12-78 months (average 35 months). CONCLUSION: Selective neck dissection is a safe and effective surgical procedure for the radical treatment of recurrent branchial anomalies.

Malignant transformation of rat bone marrow-derived mesenchymal stem cells treated with 4-nitroquinoline 1-oxide.

Recent studies indicated that extensive culture of bone marrow-derived mesenchymal stem cells (BMSCs) can lead to malignant transformation, supporting the concept that tumor may originate from adult stem cells. Also, neoplastic transformation of BMSCs induced by virus and ionizing radiation were verified. However, the capacity for BMSCs to become mutated by chemical carcinogens and become precursors of cancer is still poorly understood. In this study, BMSCs were used to test the hypothesis that tumorigenesis can originate from the mutation of stem cells induced by chemical carcinogen. BMSCs were intermittently treated with 10(-6)M 4-nitroquinoline 1-oxide (4-NQO) from population doublings level (PDL) 3 until senescence occurred. Proliferation data demonstrated that BMSCs treated with 4-NQO bypassed the senescence phase and exhibited unlimited proliferation and anchorage independence. These cells underwent a malignant transformation that resulted in tumor formation in 12/12 immunodeficient mice that received the cells by tail vein injection. In contrast, spontaneous transformation of BMSCs was observed in 6/12 immunodeficient mice injected with BMSCs that had been cultured over PDL 30 in vitro. For both BMSCs treated with 4-NQO, and BMSCs maintained in long-term culture, their transformation into neoplastic cells was found to involve chromosomal abnormalities, increased telomerase activity, and reduced, or absent, expression of p53. Our results also indicate that BMSCs are susceptible to carcinogen-induced malignant transformation rather than spontaneous transformation. Therefore, carcinogen-induced BMSCs transformation models may be ideal for studying mechanisms associated with the promotion of tumor formation by chemical carcinogens.