To assess the efficacy and mechanism of circumcision in the treatment of premature ejaculation (PE) with redundant prepuce, we enrolled a total of 81 PE patients who received circumcision. The patients' ejaculatory ability and sexual performances were evaluated before and after circumcision by using questionnaires (Intravaginal ejaculation latency time (IELT), Chinese Index of PE with 5 questions (CIPE-5) and International Index of Erectile function- 5 (IIEF-5)). Furthermore, somatosensory evoked potentials (SEPs) including dorsal nerve (DNSEP) and glans penis (GPSEP) of the patients were also measured. The mean IELTs of preoperation and post operation were 1.10±0.55 and 2.48±2.03 min, respectively (P<0.001). In addition, the geometric mean IELT after operation was 2.16 min, compared with the baseline 1.07 min before the operation, the fold increase of the IELT was 2.02. Compared with the uncircumcised status, scores of CIPE-5 showed a significant increase after circumcision (P<0.001). The mean latencies (and amplitudes) of GPSEP and DNSEP were 38.1±4.0 ms (3.0±1.9 uV) and 40.5±3.4 ms (2.8±1.6 uV) before circumcision, respectively; and 42.8±3.3 ms (2.8±1.6 uV) and 40.5±4.1 ms (2.4±1.2 uV) in the follow-up end point after circumcision. Only the latencies of GPSEP showed significant prolongation before and after circumcision (P<0.001). The ejaculation time improvement after circumcision is so small, and equal to placebo response, therefore it could not be interpreted as a therapeutic method in men with PE.

BackgroundCD1c+ tolerogenic dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) exhibit immunoregulation effects in systemic lupus erythematosus (SLE). However, the underlying immunosuppression mechanism of MSCs via tolerogenic DCs in SLE remains largely unknown.ObjectivesThe aim of this study was to examine tolerogenic DCs levels in SLE patients, and to further investigate the mechanism of MSCs in the regulation of tolerogenic DCs.MethodsTolerogenic DCs were isolated as Lin (CD3/19/56/14)- HLA DR+CD11c+CD1c+ from peripheral blood mononuclear cells (PBMCs). Levels of tolerogenic DCs were determined by flow cytometry, and serum concentration of Flt-3 ligand (FLT3L) were determined by ELISA from 17 healthy controls and 25 SLE patients. Eight SLE patients were given UC MSCs infusions. We compared the levels of tolerogenic DCs and serum FLT3L before and 24 hours after UC MSCs transplantation. PBMCs from 8 patients were collected and co-cultured with UC MSCs at ratios of 1:1, 10:1 and 50:1, for 24 hours, 48 hours and 72 hours, respectively, to detect the levels of tolerogenic DCs. The FLT3L in the supernatant solution were determined. FLT3L siRNA was added to the co-culture system, and the level of tolerogenic DCs were detected.ResultsThe levels of peripheral CD1c+ DCs and serum FLT3L were significantly decreased in SLE patients compared to healthy controls. After UC MSCs transplantation, the levels of CD1c+ DCs increased, along with an increase in serum FLT3L. In vitro studies showed that UC MSCs time-dependently up-regulated peripheral CD1c+ DCs, but not dose-dependently. The supernatant FLT3L level significantly increased after co-cultured with MSCs. However, the addition of FLT3L siRNA significantly abrogated the up-regulation of CD1c+ DCs by MSCs.ConclusionsUC MSCs induce CD1c+ tolerogenic DCs through up-regulating FLT3L in lupus patients.Disclosure of InterestNone declared

Linked Content This article is linked to Pol et al papers. To view these articles visit https://doi.org/10.1111/apt.14352 and https://doi.org/10.1111/apt.14476.

Background: Our previous study showed that apoptotic cell conditioned mesenchymal stem cells (AC-MSCs) obtained stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), but whether AC-MSCs exhibit enhanced therapeutic effect on systemic erythematosus lupus (SLE) remains unknown. In this study, we aim to explore the efficacy and possible mechanism of AC-MSCs in ameliorating SLE. Methods: Splenocytes from MRL/MPJ-Faslpr (MRL/lpr) mice were co-cultured with AC-MSCs and the proportions of plasma cells (PCs) were detected by flow cytometry. MSCs and AC-MSCs, COX2 knock-down MSCs and COX2 knock-down AC-MSCs were infused into MRL/lpr mice respectively. Survival rates and lupus symptoms including proteinuria, kidney injury, renal immune complex deposition and autoantibody production were assessed. Besides, the numbers of PCs and serum inflammatory cytokines were measured. Results: We found that AC-MSCs possessed stronger ability on PC inhibition via PGE2 in vitro. AC-MSC treatment led to significantly higher survival rate. Moreover, AC-MSC infusion decreased proteinuria levels as early as one week after infusion. Both of MSC and AC-MSC administration reduced renal immunoglobulin (Ig)G and complement C3 deposition, whereas COX2 knock-down MSCs and COX2 knock-down AC-MSCs could not. Serum anti-dsDNA antibody levels in AC-MSCs treated mice significantly decreased, as well as the number of PCs in both spleen and renal draining lymph node. In addition, AC-MSCs inhibit the production of inflammatory cytokines including interleukin (IL)-21, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. Conclusions: AC-MSCs exhibited enhanced therapeutic effects on lupus mice, which was partially mediated by COX2/PGE2. Our findings indicate that AC precondition may be a new strategy for MSC transplantation in treating SLE.

BackgroundSoluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown.ObjectivesThe aim of the present study is to explore whether sHLA-G is involved in upregulating Treg cells by MSCs, which contributes to therapeutic effects of MSCs transplantation in SLE.MethodsThe serum sHLA-G levels of SLE patients and healthy controls were detected by ELISA. The percentages of peripheral blood CD4 + ILT2 +, CD8 + ILT2 +, CD19 + ILT2 + cells and Treg cells were determined by flow cytometry. Ten patients with active SLE, refractory to conventional therapies, were infused with MSCs and serum sHLA-G was measured 24 h after infusion. Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients and co-cultured with UC-MSCs for 3 days at different ratios (50:1, 10:1, and 2:1) with or without anti-HLA-G antibodies, and the frequencies of CD4 + CD25 + Foxp3 + T cells were then determined by flow cytometry.ResultsThe concentrations of serum sHLA-G were comparable between SLE patients and healthy controls. However, there was a negative correlation between sHLA-G levels and SLE disease activity index (SLEDAI) scores in active SLE patients (SLEDAI >4). We found that serum sHLA-G levels were negatively correlated with blood urea nitrogen, serum creatinine and 24-hour urine protein in SLE patients. The sHLA-G levels were significantly lower in SLE patients with renal involvement than those without renal involvement. The expression of ILT2 on CD4 + T cells from SLE patients decreased significantly compared to that of healthy controls. A positive correlation between the frequencies of Treg and CD4 + ILT2 + T cells was found in SLE patients. The levels of sHLA-G increased 24 h after UC-MSC transplantation. The frequencies of Treg cells and the expressions of ILT2 on CD4 + Tcells were significantly increased 24 h after transplantations. In vitro studies showed that MSCs increased the frequency of Treg cells in SLE patients in a dose-dependent manner, which was partly abrogated by the anti-HLA-G antibody.ConclusionsOur results suggested that MSCs might alleviate SLE through upregulating Treg cells, which was partly dependent on sHLA-G.Disclosure of InterestNone declared