Long-term outcomes of kidney transplantation from expanded criteria donors with Chinese novel donation policy: donation after citizens' death.

INTRODUCTION: The Chinese Government initiated the Donation after Citizens' Death policy in 2010. To now, it has been a major source of organs for transplant. Since it is still a young policy, corresponding clinical evidence is still urgently needed for its improvement. Compared to kidneys donated by SCD (standard criteria donor), increasing the use of ECD (expanded criteria donor) derived kidneys is a way to expand the donor pool but is also a result of the aging demography of China. This study is based on the data of kidney transplantation in our center with the Donation after Citizens' Death policy, aiming to provide a reference for the clinical use of ECD kidneys. METHOD: A retrospective study enrolled 415 kidney transplants derived from 211 donors performed between October 2011 and October 2019. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The log-rank test was used to compare the difference in survival and postoperative complications. The Chi-square test was used to compare the occurrence of postoperative complications and postoperative renal function. The Cox regression analysis was used for risk factor screening. RESULT: Analysis showed that grafts from ECD were poorer in survival (P = 0.013), while their recipients had comparable (P = 0.16) survival. Moreover, it also was an independent risk factor for graft loss (HR 2.27, P = 0.044). There were significantly more AR occurrences in the ECD group compared with SCD group (25.0% vs. 15.8%, P = 0.004), but no significant difference was found in infection (51.9% vs. 47.6%, P = 0.497) and DGF (26.0% vs. 21.9%, P = 0.419) between them. Similarly, fewer recipients in the ECD group were free from AR within 1 year after transplantation (P = 0.040), with no statistical difference in all-cause infection prevalence in 1 year (P = 0.168). The eGFR in the ECD group was significantly worse than that in the SCD group at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant (all < 0.05), but no difference at 5 years posttransplant. Besides, results showed cardiac arrest (uncontrolled vs. controlled, HR 2.49, P = 0.049), HLA mismatch (4-6 loci vs. 0-3 loci, HR 3.61, P = 0.039), and AR occurrence (HR 2.91, P = 0.006) were demonstrated to be independent risk factors for graft loss. CONCLUSION: The ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar.

Risk factors for renal allograft survival with China novel donation category: Donation after brain death followed by cardiac arrest.

INTRODUCTION: To meet the need for transplantable organs, a new donation program was initiated by the Chinese government. This novel policy created three categories for deceased organ donations: donation after circulatory death cardiac death (DCD), donation after brain death (DBD), and donation after brain death followed by circulatory death (DBCD) meaning complete cardiac arrest. In fact, the DBCD method is a combination of both DBD and DCD methods. A DBCD donor meets the criteria of for brain death, but the organ procurement begins after the withdrawal of life support and the subsequent cardiac arrest death. The purpose of this study was to evaluate the long-term outcomes of kidney transplantation in our center with the DBCD policy. Potential risk factors for affecting the renal allograft survival were also analyzed based on our data. METHOD: A retrospective study, involving 421 kidney transplants derived from 214 donors, was conducted between December 2011 and October 2019. In particular, 373 (88.6%) transplanted organs met the criteria for DBCD, and 48 (11.4%) for DCD. The log-rank test was used to compare the difference in survival. The Cox regression analysis was used for risk factor screening. RESULT: Analysis showed that the DBCD group was better than the DCD group in terms of overall (p = 0.031) as well as death-censored (p = 0.026) allograft survival using the log-rank test. A Cox regression analysis revealed that increasing donor age (p = 0.002, HR = 1.820/10 years incremental older), increasing recipient age (p = 0.028, HR = 1.521/10 years increment older), prolonged dialysis duration (p = 0.007, HR = 1.018), occurrence episodes of acute rejection (p = 0.016, HR = 2.697), delayed graft function (p = 0.012, HR = 2.962), mismatch ≥4 HLA loci (p = 0.038, HR = 3.606), and warm ischemia time > 15 min (p = 0.022, HR = 2.915), were all independent risk factors affecting the graft survival. CONCLUSION: The new DBCD policy of donation produced acceptable results similar or even better than the DCD practice. Based on our analysis, the graft survival of DBCD transplants may be better than DCD transplants. The main risk factors for allograft loss included an increasing donor age, recipient age, warm ischemia time > 15 min, prolonged dialysis duration, acute rejection, delayed graft function, and HLA mismatch ≥4 HLA loci.

lncRNA ATXN8OS promotes breast cancer by sequestering miR­204.

Breast cancer (BC) is a common malignancy among women and the leading cause of female cancer mortality worldwide. In recent years, increasing evidence has shown that long non­coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) in human cancer and that they are involved in many biological processes, including proliferation, migration, apoptosis and invasion. In the present study, the biological function and molecular mechanism of ataxin 8 opposite strand (ATXN8OS) in BC tissue and cell lines were investigated. It was found that ATXN8OS was markedly up­regulated in BC tissue and cell lines, and that its level of overexpression was inversely linked with the overall survival rate of patients with BC. Knockdown of ATXN8OS inhibited proliferation, viability and invasion in the human MCF7 and MDA­MB­231 BC cell lines. In addition, microRNA­204 (miR­204) was negatively associated with the expression of ATXN8OS in BC tissues and cell lines. A luciferase assay demonstrated a direct binding site for miR­204 within ATXN8OS, and inhibition of miR­204 stimulated the tumour­promoting effect of ATXN8OS on BC cells. In conclusion, the present study suggested that ATXN8OS acts as a tumour promoter by sequestering miR­204 during the development of BC, therefore providing a mechanistic insight which may facilitate the diagnosis and treatment of BC.

Cell fate regulation by reticulon-4 in human prostate cancers.

Reticulon-4 (RTN4), a reticulon family protein localized in the endoplasmic reticulum, is reported to be involved in multiple physiological processes like neuroendocrine secretion and membrane trafficking in neuroendocrine cells. Previous studies have presented a great potential of RTN4 for the treatment of autoimmune-mediated demyelinating diseases and spinal cord injury regeneration. While interaction with Bcl-2 and Bcl-2-like family in apoptosis modulation implicated its possible role in various human cancers. However, the investigation of this gene in prostate cancer is mainly ignored. Here in our current study, we focused on its role in prostate cancer and found that RTN4 DNA copy numbers were higher in prostate cancer than normal prostate gland while its RNA and protein expressions were relatively lower. Chromosomal neighbor gene EML6 had similar expression patterns with RTN4 in prostate cancer tissues and cell lines, and further research found that they could be both targeted by miR-148a-3p. Lentivirus-mediated RTN4 overexpression potently inhibited DU145 and LNCaP cells proliferation. Cell cycle was blocked in G2/M phase and significant cell senescence was observed in RTN4 overexpressed prostate cancer cells. Finally, interaction networks in the normal prostate gland and cancer tissues further revealed that RTN4 maybe phosphorylated by MAPKAPK2 and FYN at tyrosine 591 and serine 107, respectively. All these results implied that RTN4 might somehow participate in prostate tumor progression, and this elicits possibility to develop or identify selective agents targeting RTN4 for prostate cancer therapy.

Loss of scinderin decreased expression of epidermal growth factor receptor and promoted apoptosis of castration-resistant prostate cancer cells.

Most patients with prostate cancer will eventually develop the castration-resistant form characterised by metastasis. Cytoskeleton constituents, including F-actin, play important roles in maintaining epithelial integrity and their disruption is a major cause of cancer progression. We previously showed that scinderin (SCIN), an important regulator of F-actin organisation, is highly expressed in poorly differentiated cancer tissues. This study aimed to explore the mechanism of its regulation of cell proliferation. We discovered that SCIN knockdown significantly downregulated epidermal growth factor receptor (EGFR) protein expression, and inhibited epidermal growth factor (EGF)-mediated cell proliferation and activation of the downstream mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signalling pathway. Silencing of SCIN promoted apoptosis in two cell lines (PC-3 and DU145), inhibited B-cell lymphoma-extra-large (Bcl-xl) expression and activated caspase signalling. Furthermore, in vivo studies showed that SCIN deletion slowed tumour growth and decreased EGFR expression. Thus, we conclude that SCIN promotes prostate cancer cell survival by stabilising EGFR and MEK/ERK signalling.

Mesenchymal stem cells drive paclitaxel resistance in ErbB2/ErbB3-coexpressing breast cancer cells via paracrine of neuregulin 1.

We had previously demonstrated that increased expression of ErbB3 is required for ErbB2-mediated paclitaxel resistance in breast cancer cells. In the present study, we have explored the possible role of mesenchymal stem cells (MSCs) in regulating the paclitaxel-sensitivity of ErbB2/ErbB3-coexpressing breast cancer cells. We show that human umbilical cord-derived MSCs express significantly higher level of neuregulin-1 as compared with ErbB2/ErbB3-coexpressing breast cancer cells themselves. Coculture or treatment with conditioned medium of MSCs not only decreases the anti-proliferation effect of paclitaxel on ErbB2/ErbB3-coexpressing breast cancer cells, but also significantly inhibits paclitaxel-induced apoptosis. We further demonstrate that this MSCs-drived paclitaxel resistance in ErbB2/ErbB3-coexpressing breast cancer cells could be attributed to upregulation of Survivin via paracrine effect of NRG-1/ErbB3/PI-3K/Akt signaling, as either specific knockdown expression of ErbB3, or blocking of downstream PI-3K/Akt signaling, or specific inhibition of Survivin can completely reverse this effect. Moreover, targeted knockdown of NRG-1 expression in MSCs abrogates theirs effect on paclitaxel sensitivity of ErbB2/ErbB3-coexpressing breast cancer cells. Taken together, our study indicate that paracrine of NRG-1 by MSCs induces paclitaxel resistance in ErbB2/ErbB3-coexpressing breast cancer cells through PI-3K/Akt signaling-dependent upregulation of Survivin. Our findings suggest that simultaneously targeting mesenchymal stem cells in tumor microenvironment may be a novel strategy to overcome paclitaxel resistance in patients with ErbB2/ErbB3-coexpressing breast cancer.

Apolipoprotein C1 promotes prostate cancer cell proliferation in vitro.

Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus-mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells. Additionally, APOC1 silencing decreased survivin, phospho-Rb, and p21 levels and increased cleaved caspase-3 expression. These data supported the procarcinogenic effects of APOC1 in the pathogenesis of PCa and suggested that targeting APOC1 may have applications in the treatment of PCa.

Knockdown of PYCR1 inhibits cell proliferation and colony formation via cell cycle arrest and apoptosis in prostate cancer.

Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism, which has been shown to be up-regulated in cancers. However, the functions of PYCR1 in prostate cancers (PCa) are still largely unknown. In the present study, we found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. Both qRT-PCR and western blotting indicated that PYCR1 was suppressed efficiently after sh-PYCR1 infection. Further analysis indicated knockdown of PYCR1 significantly inhibited PCa cell growth and colony formation ability. The inhibition effects on growth were likely due to G2/M-phase arrest and enhanced cell apoptosis, as determined by flow cytometer analysis. At last, we verified the expression levels of cell cycle regulatory proteins, including CDK1, CDK2, CDK4 and Cyclin B1 were all downregulated and cell apoptotic-related proteins, including cleaved caspase 3 and cleaved PARP were increased in PCa cells after PYCR1 knockdown. Furthermore, PYCR1 has been shown not to be directly regulated by androgen receptor (AR) levels. These results show the functions of PYCR1 in PCa tumorigenesis for the first time and suggest that PYCR1 might be a good potential therapy approach for treating PCa.

MYO6 knockdown inhibits the growth and induces the apoptosis of prostate cancer cells by decreasing the phosphorylation of ERK1/2 and PRAS40.

Prostate cancer is the second most frequently diagnosed cancer among males around the world. Myosin VI (MYO6), as a motor protein, has been reported to be implicated in cancer-related cell migration and cellular functions. To investigate the role of MYO6 in prostate cancer, immunohistochemical analysis was firstly applied to prostate cancer tissues and revealed that MYO6 was closely related with the Gleason score in prostate cancer. Then we used specific short hairpin RNA (shRNA) to downregulate MYO6 expression in DU145 and PC-3 cells and found that decreased MYO6 expression significantly suppressed cell proliferation, as determined by MTT and colony formation assays. Flow cytometry confirmed that the suppression of MYO6 promoted cell cycle arrest at the G2/M and sub-G1 phase in the DU145 cells. Furthermore, PathScan intracellular signaling array analysis demonstrated that the phosphorylation of ERK1/2 and PRAS40 was downregulated in the DU145 cells following MYO6 knockdown. Knockdown of MYO6 downregulated the expression of AKT3 and upregulated the expression of PARP, as confirmed by western blot analysis. These results suggest that MYO6 plays an essential role in the progression of prostate cancer and silencing of MYO6 may be a promising therapeutic approach for prostate cancer.

Treatment of radiation-induced acute intestinal injury with bone marrow-derived mesenchymal stem cells.

The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P<0.01), mildly reduced body weight and plasma citrulline levels, significantly more rapid recovery (P<0.01), significantly reduced expression of the cytokines PGE2 and IL-2 (P<0.05) and significantly increased SDF-1 expression (P<0.01) compared with the control group. In summary, the present results indicate that BMSCs are able to effectively reduce inflammation and promote repair of the structure and function of intestinal tissues damaged by radiation exposure, suggesting that they may provide a promising therapeutic agent.

MicroRNA-mediated epigenetic targeting of Survivin significantly enhances the antitumor activity of paclitaxel against non-small cell lung cancer.

Elevated expression of Survivin correlates with poor prognosis, tumor recurrence, and drug resistance in various human cancers, including non-small cell lung cancer (NSCLC). The underlying mechanism of Survivin upregulation in cancer cells remains elusive. To date, no Survivin-targeted therapy has been approved for cancer treatment. Here, we explored the molecular basis resulting in Survivin overexpression in NSCLC and investigated the antitumor activity of the class I HDAC inhibitor entinostat in combination with paclitaxel. Our data showed that entinostat significantly enhanced paclitaxel-mediated anti-proliferative/anti-survival effects on NSCLC cells in vitro and in vivo. Mechanistically, entinostat selectively decreased expression of Survivin via induction of miR-203 (in vitro and in vivo) and miR-542-3p (in vitro). Moreover, analysis of NSCLC patient samples revealed that the expression levels of miR-203 were downregulated due to promoter hypermethylation in 45% of NSCLC tumors. In contrast, increased expression of both DNA methytransferase I (DNMT1) and Survivin was observed and significantly correlated with the reduced miR-203 in NSCLC. Collectively, these data shed new lights on the molecular mechanism of Survivin upregulation in NSCLC. Our findings also support that the combinatorial treatments of entinostat and paclitaxel will likely exhibit survival benefit in the NSCLC patients with overexpression of DNMT1 and/or Survivin. The DNMT1-miR-203-Survivin signaling axis may provide a new avenue for the development of novel epigenetic approaches to enhance the chemotherapeutic efficacy against NSCLC.

Bone marrow mesenchymal stem cell implantation for the treatment of radioactivity­induced acute skin damage in rats.

The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation­induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later. Then the wound healing of each rat was observed. The expression of transforming growth factor (TGF)­ß1, stromal cell­derived factor-1 (SDF­1) and prostaglandin E2 (PGE2) in the wounded tissues was determined by immunohistochemistry. The results demonstrated that skin damage was milder in the BMSC group than in the control group. Moreover, the speed of healing in the BMSC group was better than that in the control group. In addition, the wound score, it was significantly lower in the BMSC group than in the control group (P<0.05). The expression of PGE2 and TGF­ß1 in the BMSC group was also significantly lower than that in the control group (P<0.05), whereas the SDF­1 expression was significantly higher in the BMSC group than that in the control group (P<0.05). BMSCs can effectively reduce inflammation and fibrosis in the wounded skin and promote the repair of acute radioactive skin injury. Thus, may be developed as a novel treatment for wound healing.

Expression levels of Notch1 and Delta-like 4 in peripheral lymphocytes and their relationship with T helper 17 (Th17) cells in renal transplant recipients.

OBJECTIVE: This study aimed to investigate the role of the Notch1/Delta-like 4 signaling pathway and its relationship with T helper 17 (Th17) cells in the peripheral transplantation immune of renal transplant recipients. METHODS: Fifty-two kidney transplant recipients in our hospital were selected and divided into the acute rejection group (AR), renal tubular necrosis (ATN) group, and stable renal function group, according to their postoperative recovery. Flow cytometry was used to detect the expression of Notch1 and Delta-like 4 in peripheral lymphocytes and the presence of Th17 cells in the kidney of transplant recipients. RESULTS: The expression levels of Notch1 and Delta-like 4 and level of Th17 cells among the three groups before surgery and at postoperative day 1 showed no significant differences (P>0.05). At 3, 7, and 14d after surgery, these three factors in the AR group were significantly higher than in the stable renal function group (P<0.01) and ATN group (P<0.01), where the levels in the latter two groups were similar. Upon the occurrence of acute rejection, the Notch1 and Delta-like 4 expression and Th17 cell ratio were significantly increased (P<0.01) but gradually decreased after anti-rejection therapy. Notch1 and Delta-like 4 were significantly positively correlated with Th17 cells (r=0.893, P<0.01 and r=0.893, P<0.01, respectively). CONCLUSION: The detection of Notch1 and Delta-like 4 expression in peripheral blood lymphocytes of renal transplant recipients can serve as a positive indicator for evaluating the diagnosis and treatment efficacy of the AR reaction.

[PPAR-γ agonist inhibits the expressions of chemokines induced by IFN-γ and TNF-α in renal tubular epithelial cells].

OBJECTIVE: To investigate the effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist 15d-PGJ2 on the expressions of CXCL9, CXCL10 and CXCL11 in renal tubular epithelial cells (HK-2) stimulated by interferon-γ (IFN-γ) plus tumor necrosis factor-α (TNF-α). METHODS: HK-2 cells were stimulated with IFN-γ plus TNF-α only, or incubated with 15d-PGJ2 for 48 hours. CXCL9, CXCL10 and CXCL11 expressions were determined by real-time quantitative PCR (qRT-PCR) and ELISA. RESULTS: IFN-γ plus TNF-α increased mRNA and protein expressions of CXCL9, CXCL10 and CXCL11 in HK-2 cells. PPAR-γ agonist 15d-PGJ2 inhibited the expressions of CXCL9, CXCL10 and CXCL11 in IFN-γ combined with TNF-α-induced HK-2 cells. Compared with the IFN-γ plus TNF-α group (untreated with 15d-PGJ2), the CXCL9, CXCL10 and CXCL11 were depressed by 76.8%, 78.7% and 81.9% at mRNA level and 66.9%, 86.6% and 39.9% at protein level in 2.0 ng/mL 15d-PGJ2-treated HK-2 cells, respectively (P<0.05). CONCLUSION: PPAR-γ agonist 15d-PGJ2 could inhibit CXCL9, CXCL10 and CXCL11 production induced by IFN-γ combined with TNF-α in HK-2 cells.

Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma.

PURPOSE: This study aimed to investigate the expression of p53 and Ki67 genes in renal cell carcinoma (RCC) and its possible clinical value. METHODS: A retrospective analysis of clinical data from 1239 patients with RCC was performed to explore the relationship between the expression of Ki67 and p53 proteins and tumor stage, grade and prognosis. RESULTS: p53 expression was not significantly correlated with TNM stage and Fuhrman grade (p>0.05); Ki67 expression was significantly correlated with TNM stage and Fuhrman grade (p<0.05). Kaplan-Meier and log-rank survival rate results showed that the prognosis of Ki67 and p53 double-positive group was significantly inferior to the single-positive and negative group (p<0.001). In the multivariate Cox risk regression analysis model, TNM stage, relative risk/RR=3.196, p<0.001), Fuhrman grade (RR=3.196, p<0.001) and Ki67 and p53 double-positive [Ki67 (+) p53 (+) , RR=3.196, p<0.001] were significantly correlated with tumor prognosis, and independent predictors of the patient disease-free survival (DFS). CONCLUSION: The combined detection of p53 and Ki67 expressions, which are superior to single marker, could be used to improve significantly the accuracy of prognosis of RCC patients.

Characterization of a water-soluble polysaccharide from Boletus edulis and its antitumor and immunomodulatory activities on renal cancer in mice.

A polysaccharide (BEP, Mw=113,432Da) was purified from Boletus edulis, which had a backbone consisting of (1→6)-linked-α-d-glucopyranosyl, (1→2,6)-linked-α-d-galactopyranosyl, (1→6)-linked-α-d-galactopyranosyl, and (1→3)-linked-α-d-rhamnopyranosyl residues, which were branched at O-2 position of (1→2,6)-linked-α-d-galactopyranosyl residue with a single terminal (1→)-linked-α-l-arabinofuranosyl residue. After 32 days' BEP administration to Renca tumor bearing mice, the tumor mass of Renca transplanted in mice was significantly repressed. Furthermore, BEP could significantly increase the spleen and thymus indices, stimulate splenocytes proliferation, augment NK cell and CTL activities in spleen, and promote the secretion of the cytokines IL-2 and TNF-α in Renca tumor bearing mice. Meanwhile oral administration of BEP (100 and 400mg/kg) restored all the altered hematological and biochemical parameters of tumor-bearing mice to normal levels. Thus, these data demonstrate that BEP possesses potential immunomodulatory activity and might be employed as effective therapeutic agents for the prevention of renal caner.

Prognostic factors for renal allograft survival in patients with immunoglobulin A nephropathy: a case control study.

The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.

Plasmakinetic enucleation of the prostate compared with open prostatectomy for prostates larger than 100 grams: a randomized noninferiority controlled trial with long-term results at 6 years.

BACKGROUND: Studies have demonstrated that plasmakinetic enucleation of the prostate (PKEP) and open prostatectomy (OP) have equivalent short-term efficacy for large prostates, but no comparison concerning their long-term results was reported. OBJECTIVE: To demonstrate the noninferiority of PKEP to OP concerning maximum urinary flow rate (Qmax) at 1 yr postoperatively and to compare the long-term results of both procedures. DESIGN, SETTING, AND PARTICIPANTS: From 2004 to 2007, 160 patients with prostates >100g were randomized to receive PKEP or OP. A total of 153 patients (95.6%) completed the noninferiority study, and 123 patients (76.9%) finished a 6-yr follow-up assessment. INTERVENTION: The PKEP procedures were performed with 27F Karl Storz continuous flow resectoscopy and the Gyrus PlasmaKinetic device. OP was performed by a suprapubic transvesical approach. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was Qmax at 1 yr postoperatively. Secondary end points included other perioperative parameters and postoperative micturition variables. The student t test, Mann-Whitney U test, chi-square test, or Fisher exact probability test was used as appropriate. RESULTS AND LIMITATIONS: PKEP was noninferior to OP regarding Qmax at 1 yr postoperatively. Compared with OP, PKEP was associated with less perioperative hemoglobin decrease, shorter catheterization time, and shorter postoperative hospital stay (1.0 vs 3.2g/dl, 40 vs 148h, and 3 vs 8 d, respectively; p<0.001 for all), as well as fewer short-term complications (22.5% vs 42.5%, p=0.031). On intention-to-treat analysis, both the PKEP and OP groups had equivalent Qmax (25.2±7.0ml/s vs 25.7±7.6ml/s, respectively; p=0.688), International Prostate Symptom Score (3.5 [2-5] vs 3 [2-5], respectively p=0.755), quality of life (2 [1-3] vs 2 [1-3], respectively; p=0.950), and postvoid residual urine (20 [9-33.5] vs 16.5 [7-31] ml, respectively; p=0.469) at 72 mo postoperatively. No patients required reoperation because of recurrence of BPH. The relatively small sample size is the limitation. CONCLUSIONS: PKEP is a durable procedure with short- to long-term micturition improvement equivalent to OP and significantly lower perioperative morbidity. PATIENT SUMMARY: We compared PKEP with OP for large prostates and found that PKEP is less invasive, with short- to long-term micturition improvement equivalent to OP. TRIAL REGISTRATION: Plasmakinetic Enucleation of the Prostate and Open Prostatectomy to Treat Large Prostates. ClinicalTrials.gov identifier NCT01952912. http://www.clinicaltrials.gov/ct2/show/NCT01952912?term=NCT016301952912&rank=1.

Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms.

BACKGROUND AIMS: Minimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired. METHODS: The adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time-polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry. RESULTS: MSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group. CONCLUSIONS: Our data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.

Suppression of SCIN inhibits human prostate cancer cell proliferation and induces G0/G1 phase arrest.

SCIN is a calcium regulated actin severing and capping protein. Its homologue in zebrafish is found to be related with cell death. In the present study, we found that SCIN is highly expressed in human prostate cancer specimens. However, the functions of SCIN in human prostate carcinoma cells are largely unknown. To address the function of SCIN in prostate carcinoma cells, we used lentivirus-mediated RNAi to knock down SCIN expression in PC3 cells, a prostate carcinoma cell line. We found that in vitro silencing of SCIN could inhibit the proliferation and colony formation ability of PC3 cells. Furthermore, cell cycle analysis showed that reduced SCIN expression lead to G0/G1 cell cycle arrest through the regulation of cell cycle-related genes, such as p21Waf1/Cip1, cyclin-dependent kinase inhibitor 2A (CDKN2A, p16Ink4A) and cyclin A2. These results suggest that SCIN plays an important role in the proliferation of prostate cancer cells and lentivirus-mediated inhibition of SCIN expression may be a potential therapeutic method for the treatment of prostate cancer.