Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Effects of Long Noncoding RNA HOXA-AS2 on the Proliferation and Migration of Gallbladder Cancer Cells.

To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3'UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (p < 0.05). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3'UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.

Ablation of Basic Leucine Zipper Transcription Factor ATF-Like Potentiates Estradiol to Induce Atopic Dermatitis.

Background: Atopic dermatitis (AD) is an inflammatory and immune skin disorder. Basic leucine zipper transcription factor ATF-like (BATF) plays a key role in regulating the differentiation and functions of lymphocytes. However, the mechanism underlying the transcriptional regulation of BATF on AD is still not well understood. Methods: BATF knockout (BATF-/-) and C57BL/6(B6) mice were used for the development of spontaneous dermatitis. 17ß-Estradiol was injected intraperitoneally to induce AD. The lesioned tail skin of the mice was stained with hematoxylin and eosin to analyze the pathological characteristics. Impaired skin barrier function was assessed by measuring the transepidermal water loss (TEWL). The skin epithelial barrier indicators and cytokine mRNA levels were quantified by real-time quantitative PCR. The total serum immunoglobulin E (IgE) levels were measured by enzyme-linked immunosorbent assay (ELISA). T lymphocytes were analyzed using flow cytometry. Results: Ablation of BATF led to the spontaneous development of AD only in female mice and not in male mice. BATF deletion led to elevated serum levels of IgE and increased infiltration of eosinophils, neutrophils, and lymphocytes and promoted cytokine production including IL-4, IL-22, IL-1ß, IFN-γ, and TNF-α in the lesioned tail skin of the mice. The mRNA expression levels of filaggrin and loricrin significantly decreased, while S100A8 and S100A9 increased in female BATF-/- mice. BATF-deficient female mice were found to increase proliferation and IL-5 production by skin-infiltrating CD4+ T cells which implies Th2 activation. Moreover, AD was successfully induced only in the estradiol-treated BATF-deficient male mice and not in WT male mice. Estradiol enhanced the allergic and immunological responses to dermatitis primarily by triggering Th2-type immune responses via enhanced serum IgE and inflammatory cytokine levels in the male BATF-/- mice. Conclusion: The study concluded that BATF potentiates estradiol to induce mouse atopic dermatitis via potentiating inflammatory cytokine releases and Th2-type immune responses and may have important clinical implications for patients with AD.

Simultaneous antegrade urography of the upper urinary tract and retrograde cystography combined with computed tomography imaging in the management of ureteral complications after renal transplantation.

BACKGROUND: To investigate the significance of simultaneous urography of the upper and lower urinary tract of transplanted kidneys combined with computed tomography urography (CTU), computed tomography arteriography (CTA), and computed tomography venography imaging in the planning of open surgery performed to treat any ureteral complications of a transplanted kidney. METHODS: In all, 24 patients with ureteral complications after renal transplantation were admitted, 12 of whom had renal graft ostomy during open surgery. Simultaneous antegrade urography of the upper urinary tract and retrograde cystography of the transplanted kidneys were performed on the patients. With the use of computed tomography imaging results, surgical planning was carried out. RESULTS: All surgeries were successfully completed according to preoperative planning. Three patients underwent end-to-end anastomosis of the ureter and bladder muscle flap, 8 patients underwent ureterocystostomy, and 1 patient underwent an end-to-end ureteral anastomosis. After the follow-up up to now, all the patients had stable renal function, and no complications such as ureteral stenosis or urine leakage have thus far reoccurred in the transplanted kidneys. CONCLUSIONS: When open surgery is required to treat any ureteral complications following renal transplantation, preoperative multiangle imaging can be used to better understand the condition of the transplanted urinary tract and thus aid considerably in surgical planning.

Effect of disseminated intravascular coagulation on donation after citizens' death donor kidneys.

BACKGROUND: To investigate the effect of disseminated intravascular coagulation (DIC) on donor kidney in donation after citizens' death (DCD) donors. METHODS: The clinical and laboratory data of 159 DCD donors obtained by our center in 2018 were retrospectively analyzed. The DIC diagnosis was performed according to the Chinese DIC scoring system (CDSS). The donors were divided into two groups: DIC (+) and DIC (-). The difference between kidney rejection rate and zero puncture glomerular microthrombus formation rate were compared. RESULTS: Among the 159 DCD donors, 11 were discarded (accounting for 6.91%). The reasons for the discarded cases included 5 cases (3.14%) for moderate and severe glomerular microthrombus formation in the renal zero puncture pathology; 2 cases (1.26%) for glomerular sclerosis ratio over 50%; 2 cases (1.26%) for long-term low blood pressure before pregnancy and significantly increased serum creatinine level and no urine; 1 case (0.73%) for kidney stones and stagnant water; 1 case (0.63%) for malignant tumor. The donor rejection rate of the DIC (+) group was higher than that of the DIC (-) group, and the difference was statistically significant (P<0.05). Among all donors, 10 cases (6.29%) were found to have glomerular microthrombus at zero puncture, and the microthrombotic rate in the DIC (+) group was significantly higher than that in the DIC (-) group (P<0.05). Of the 10 microthrombotic donors, 5 donors with severe glomerular microthrombus were discarded. CONCLUSIONS: Donor-induced DIC can easily cause renal glomerular microthrombus formation, and the donor kidney rejection rate has increased.

Reconstruction of the hepatic artery using the superior mesenteric artery for liver transplantation.

BACKGROUND: To investigate the application of the superior mesenteric artery (SMA) for the in vitro reconstruction of the hepatic artery for liver transplantation, and to improve the success rate and safety of donor liver transplantation. METHODS: The donor liver and the pancreas were obtained, and the SMA and its branches were used to reconstruct the hepatic artery. Liver transplantation was performed after reconstruction to understand the intraoperative situation after donor liver opening, as well as postoperative liver function. Color Doppler ultrasound of the transplanted liver was also performed. RESULTS: During the period from September 2016 to March 2020, a total of 98 pancreases were obtained. The common hepatic artery and gastroduodenal artery loop (CHA-GDA) were preserved to the donor pancreas, and only the proper hepatic artery (PHA) or left/right hepatic artery (LHA/RHA) were preserved to the donor liver. If the PHA of the donor liver was short or absent, the SMA was used for lengthening the PHA or in vitro reconstruction of the LHA/RHA, followed by implantation of the donor liver after reconstruction. A total of 17 cases of this type of donor liver required mesenteric artery lengthening or reconstruction. After opening, the donor liver was well-filled, bile secretion was normal, and liver function recovered as scheduled after surgery. Color Doppler ultrasound and CT angiography (CTA) of the transplanted liver revealed that hepatic arteries were normal without complications such as hepatic artery embolism. CONCLUSIONS: In vitro reconstruction of the hepatic artery with the SMA is an effective new method of vascular reconstruction, which ensures the blood flow of the hepatic artery, reduces the anastomosis difficulty of the arteries of the donor liver, and reduces the occurrence of vascular complications.

Blockade of OX40/OX40L pathway combined with ethylene-carbodiimide-fixed donor splenocytes induces donor-specific allograft tolerance in presensitized recipients.

BACKGROUND: Memory T cells (Tms) are the major barrier preventing long-term allograft survival in presensitized transplant recipients. The OX40/OX40L pathway is important in the induction and maintenance of Tms. METHODS: In this study, we added anti-OX40L mAb to ethylene-carbodiimide-fixed donor splenocytes (ECDI-SPs)-a method which is effective in inducing allograft tolerance in non-presensitized mouse heart transplant model. Recipient mice received heart transplantation after 6 weeks of donor skin presensitization and were treated with anti-OX40L mAb, ECDI-SPs or anti-OX40L mAb + ECDI-SPs, respectively. RESULTS: Our data showed that the combination of ECDI-SPs and anti-OX40L mAb induced donor-specific tolerance in skin-presensitized heart transplant recipients, with the mechanism for this being associated with suppression of Tms and upregulation of CD4+CD25+Foxp3+ T regulatory cells (Tregs). Importantly, CD25+ T-cell depletion in the combined therapy-treated recipients broke the establishment of allograft tolerance, whereas adoptive transfer of presensitization-derived T cells into tolerant recipients suppressed Tregs expansion and abolished established tolerance. CONCLUSIONS: Blockade of OX40/OX40L pathway in combination with ECDI-SPs appears to modulate the Tms/Tregs imbalance so as to create a protective milieu and induce graft tolerance in presensitized recipients.

Impact of the use of vasoactive drugs in cardiac death donors on the early postoperative renal function and related complications in renal transplant recipients.

BACKGROUND: To explore the impact of the use of vasoactive drugs in donation after cardiac death (DCD) donors on graft function, with an attempt to guide the clinical practices of organ preservation and DCD kidney transplantation. METHODS: The clinical data of 187 DCD donors and 304 recipients who were operated on in our center from February 2018 to May 2019 were retrospectively analyzed. Based on whether vasoactive drugs were used for maintaining blood pressure in DCD donors, the renal donors and recipients were divided into a high-dose group (norepinephrine ≥1.3 µg/kg/min or in combination with dopamine), a low-dose group (norepinephrine <1.3 µg/kg/min or in conjunction with dopamine), and a no-medication group (without the use of vasoactive drugs). The clinical features, post-transplant renal function, and complications were compared among these three groups. RESULTS: The early renal function 1 and 7 days after surgery was significantly superior in the high-dose group and no-medication group (P<0.05) but showed no significant difference between the low-dose group and the no-medication group (P>0.05). Blood urea nitrogen (BUN) on the 1st postoperative days was significantly higher in the high-dose group than in the low-dose group and the no-medication group (P<0.05). Renal function indicators, including serum creatinine (CRE), BUN, and blood uric acid (UA) on the 30th postoperative day, showed no significant difference among these three groups (P>0.05). The incidence of delayed graft function (DGF) after renal transplantation was significantly higher in the high-dose group than in the low-dose group and the no-medication group (P<0.05), whereas there was no significant difference between the groups in the incidences of graft rejection and infections (P>0.05). CONCLUSIONS: The use of vasoactive drugs in DCD donors can affect the early recovery of renal function in renal transplant recipients, particularly for those donors who are administered a high dose of vasoactive drugs. Therefore, donor maintenance should be performed cautiously with vasoactive drugs.

A PSCA/PGRN-NF-κB-Integrin-α4 Axis Promotes Prostate Cancer Cell Adhesion to Bone Marrow Endothelium and Enhances Metastatic Potential.

Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)-positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases. IMPLICATIONS: The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.

Correlation between use of immunosuppressive agents and transplant-acquired allergies in renal transplant recipients.

BACKGROUND: Although immunosuppressive agents used in recipients of organ transplants can suppress T cell immune responses, type I allergy to ingested or inhaled allergens after organ transplantation have frequently been reported in pediatric patients. This study aims to investigate the relationship between the use of immunosuppressive agents and the transplant-acquired allergy (TAA) in adult renal transplant recipients (RTRs). METHODS: Seventy-nine RTRs treated in our hospital from February 2015 to February 2016 were interviewed for allergic diseases by using a standard questionnaire. UniCAP allergen screening tests were performed to detect total IgE and specific IgE levels before and after renal transplantation after the use of calcineurin inhibitor tacrolimus (FK506) or cyclosporin A (CsA). The follow-up visits were scheduled for 6 months, 1 year, 2 years, and 3 years after transplantation. RESULTS: Allergen sensitization occurred in 9 of 79 patients. Among them, the sensitization occurred in 2 cases within 6 months after renal transplantation, in 1 case from 6 months to 1 year, in 3 cases from 1 to 2 years, and in 3 cases from 2 to 3 years. The majority of sensitization was induced by inhaled allergens (n=7), among whom 3 patients (3/79, 3.8%) had a history of type I allergy, which occurred within 6 months after transplantation in 2 cases (allergic dermatitis) and from 2 to 3 years in 1 case (diarrhea after peanut allergy). The total IgE levels of RTRs using immunosuppressive agents at different time points including 6 months, 1 year, 2 years, and 3 years after renal transplantation were significantly lower than that before surgery (all P<0.05). Sensitization occurred in 8 RTRs using FK506 and in 1 patient treated with CsA (P=0.432), and allergies occurred in 3 RTRs using FK506 and were not found among CsA users (P=0.561). CONCLUSIONS: Administration of immunosuppressive agents in adult RTRs cannot wholly prevent allergy or sensitization. Studies with larger sample sizes and more extended follow-up periods are still required to further explore the potential association between the use of FK506 and CSA and the allergies or sensitization.

Complications and clinical management of ultrasound-guided renal allograft biopsies.

BACKGROUND: In this paper, the regular flow of ultrasound-guided renal allograft biopsies was established by analyzing complications and clinical management principle of ultrasound-guided renal allograft biopsies, to increase the safety of ultrasound-guided renal allograft biopsies. METHODS: The purpose of this study was to analyze the cases of ultrasound-guided renal allograft biopsies in our hospital from January 2006 to October 2018 because of abnormal renal function (including symptoms of albuminuria and elevated serum creatinine). The type of puncture needle used in renal allograft biopsies, the number of puncture needle and the relationship between puncture needle and complication were counted, and the treatment measures were analyzed. RESULTS: From January 2006 to October 2018, a total of 487 patients underwent ultrasound-guided renal allograft biopsies in our hospital. Among them, the successful sampling rate was 98.8%, and the average number of glomeruli per specimen was 15.24±2.26. The complications of the patient after puncture included: perirenal hematomas, subcapsular hematomas, acute ureter obstruction caused by hematuria, gross hematuria, and microscopic hematuria. Among them, two patients were treated with open surgery to save the function of renal transplantation, and the primary treatment measures were to increase the absolute bed rest time. The symptoms of the patients were relieved after treatment. CONCLUSIONS: The analysis showed that ultrasound-guided renal allograft biopsies are safe and feasible, and the analysis of the biopsies of patients can provide meaningful pathological information for the clinic.

Pancreas allograft biopsies procedure in the management of pancreas transplant recipients.

Pancreas transplantation is an effective therapy for diabetic patients, which can significantly improve the survival rate and quality of life of diabetic patients. According to the international registration of pancreas transplantation center, the global total pancreas transplantation has reached more than 80,000 cases by 2017, including pure pancreas transplantation and simultaneous pancreas-kidney transplantation (SPK). With the development and application of a new type of immunosuppressant, with the gradual maturity of organ preservation technology and surgical technology, the pancreas transplantation has rapidly on a global scale. However, pancreas transplantation still has more problems than limit its development compared with other organ transplantation. For example, the early diagnosis and treatment of pancreatic rejection are of considerable significance to the prognosis of pancreas transplantation. Some surveillance methods of diagnosis have been used increasingly, among which the histopathological diagnosis is particularly important. The first Banff schema for the histological diagnosis of pancreas rejection has been published, which primarily dealt with the diagnosis of acute T-cell-mediated rejection (ACMR). In recent years, antibody-mediated rejection (AMR) has been more emphasized as the primary cause of graft failure. The Banff pancreas allograft rejection grading schema was updated in 2011 by a broad-based multidisciplinary panel, presenting comprehensive guidelines for the diagnosis of AMR.

Thulium (Tm:YAG) laser vaporesection of prostate and bipolar transurethral resection of prostate in patients with benign prostate hyperplasia: a systematic review and meta-analysis.

Thulium laser vaporesection (ThuVARP) and bipolar transurethral resection of the prostate (B-TURP) are novel surgeries for benign prostate hyperplasia (BPH). This paper is a systematic review and analysis of literatures comparing efficacy indicators, operative parameters, as well as safety indicators between ThuVARP and B-TURP for the treatment of BPH. A systematic search of electronic databases, including PubMed, the Cochrane Library, Web of Science, Embase, and China National Knowledge Internet (CNKI), was carried out up to December 1, 2015 (updated on March 1, 2016). The captivating outcomes included basic clinical characteristics, perioperative parameters, local complications, and efficacy indicators which included International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR). After assessing the quality of methodology and extracting data, a meta-analysis was carried out by using STATA 12.0 software. Five studies involving 500 patients met the standard. The outcomes of this analysis were as follows: (a) efficacy indicators: there were no significant differences in IPSS, QoL, PVR, and Qmax between the two groups (all P > 0.05); (b) perioperative indicators: ThuVARP had longer operative time [standardized mean difference (SMD) = 0.843; 95% confidence interval (CI) - 0.391, 1.296; P < 0.001] but less serum hemoglobin decreased (SMD = - 0.561; 95% CI - 0.796, - 0.327; P < 0.001), shorter hospital stay (SMD = - 1.558; 95% CI - 2.709, - 0.407; P < 0.01), and catheterization time (SMD = - 1.274; 95% CI - 2.158, - 0.390; P < 0.01). Additionally, no significant difference was found in estimated resected weight (P > 0.05); (c) safety indicators: no significant difference was found in local complication rates (all P > 0.05) between ThuVARP and B-TURP. In our analysis, there exists no statistical difference between ThuVARP and B-TURP group in efficacy. However, in spite of requiring longer surgical time, ThuVARP was better in terms of less blood loss as well as shorter hospitalization and catheterization time.

Use of the ureteral access sheath during ureteroscopy: A systematic review and meta-analysis.

The debate still rages on for the usefulness of ureteral access sheath (UAS). Therefore, a meta-analysis to discuss the effects of applying UAS during ureteroscopy was performed. The protocol for the review is available on PROSPERO (CRD42017052327). A literature search was conducted up to November, 2017 using the Web of science, PUBMED, EMBASE and Cochrane Library. The quality of articles was assessed by the Jadad scale and Newcastle Ottawa Scale (NOS). Egger's test and the trim-and-fill method were used to evaluate publication bias. Effect sizes were calculated by pooled odds ratio (ORs) and mean differences (MDs). Sensitivity analyses and subgroup analyses were performed to explore the origin of heterogeneity. Eight trials with a total of 3099 patients and 3127 procedures were identified. Results showed no significant difference in stone-free rate (SFR) (OR = 0.83, 95% CI 0.52-1.33, P = 0.45), intraoperative complications (OR = 1.16, 95% CI 0.81-7.69, P = 0.88), operative time (MD = 4.09, 95% CI -15.08-23.26, P = 0.68) and hospitalization duration (MD = -0.13, 95% CI -0.32-0.06, P = 0.18). However, the incidence of postoperative complications was higher in UAS group (OR = 1.46, 95% CI 1.06-2.00, P = 0.02). Evidence from meta-analysis indicated that the use of UAS during ureteroscopy did not manifest advantages. However, given the intrinsic restrictions of the quality of selected articles, more randomized controlled trials (RCTs) are warranted to update the findings of this analysis.

PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc.

BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems. RESULTS: Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation. CONCLUSIONS: PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.

PSCA regulates IL-6 expression through p38/NF-κB signaling in prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. We previously reported that PSCA involved in proliferation and invasion of PCa cells, however, the underlying mechanisms are unknown. In this study, we aimed to explore the regulating role of PSCA gene expression in interleukin-6 (IL-6) autocrine of PCa cells. METHODS: The stable knockdown-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa DU145 and PC-3M cells. The effects of PSCA overexpression or knockdown were determined in proliferation, invasion, and metastasis assays. The effect of PSCA on the expression and secretion of IL-6 was evaluated by immunoblotting and ELISA. Subcellular localization and expression pattern of PSCA and IL-6 protein were examined by immunohistochemistry. Its clinical significance was statistically analyzed. RESULTS: The results showed that stable knockdown of PSCA delayed proliferation, migration, and invasion while overexpressing PSCA enhanced the proliferation, migration, and invasion in vitro and the lung metastasis in vivo of PCa cells. Importantly, the PSCA involved in the IL-6 secretion and positively regulated p38/NF-κB/IL-6 signaling, leading to enhanced PCa cell invasion and metastasis. Both the expression of PSCA and IL-6 were significantly associated with poor biochemical recurrence-free survival of patients with PCa. PSCA protein expression showed a prognostic value in overall survival as indicated by Kaplan-Meier analysis. CONCLUSIONS: These results indicate that PSCA regulates the expression and secretion of IL-6 in human PCa cells through p38/NF-κB signaling pathways. PSCA may be a potential diagnostic marker and therapeutic target for PSCA-positive PCa.

Predictors for uroseptic shock in patients who undergo minimally invasive percutaneous nephrolithotomy.

To identify risk factors that can predict which patient is likely to progress from systemic inflammatory response syndrome (SIRS) to uroseptic shock after minimally invasive percutaneous nephrolithotomy (MPCNL) for the upper urinary tract stones. We retrospectively reviewed 156 patients who suffered infectious complications after MPCNL from March 2014 to February 2016. Perioperative risk factors that could potentially contribute to uroseptic shock were compared to those of patients with only SIRS. 135 of the 156 patients developed to SIRS only, the remaining 21 patients progressed to uroseptic shock. The rate of positive preoperative urine nitrite was significantly higher (p < 0.001), stone diameter was larger (p = 0.015) and operative time was longer (p < 0.001) in uroseptic shock group. Multivariable logistic analysis showed that preoperative urine nitrite (OR 10.570, p = 0.025), stone size (OR 11.512, p = 0.009) and postoperative blood leukopenia (OR 0.009, p < 0.001) were independently related to uroseptic shock. Moreover, ROC curve analysis showed that white blood count threshold within the first 3 h of uroseptic shock was 2.98 × 109/L. The sensitivity and specificity of leukocyte count in predicting uroseptic shock were 90.5 and 92.6%, respectively. Preoperative urine nitrite, stone size and postoperative leukocyte count are statistically linked to uroseptic shock after MPCNL. Leukopenia of less than 2.98 × 109/L within 3 h after MPCNL can be a predictor for uroseptic shock. For patients who have high risk factors for developing uroseptic shock, the white blood count should be measured within 3 h after MPCNL.

Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido. RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

Knockdown of PSCA induces EMT and decreases metastatic potentials of the human prostate cancer DU145 cells.

BACKGROUND: Prostate stem cell antigen (PSCA) expression has been shown to correlate with prostatic carcinogenesis and prostate cancer (PCa) progression. The underlying mechanisms for these processes are currently unknown. Epithelial to mesenchymal transition (EMT) has been associated with the invasiveness and the distant metastasis of PCa. In this study, we investigated the effects of knocking down the PSCA on the cell migration, the invasiveness, and the EMT of the PCa cell line DU145 in vitro and in vivo. METHODS: Four target sequences of the small hairpin RNA for PSCA were designed, and the best effect knockdown sequence shRNA#1 was screened to construct the stable transfected DU145 cell line (DU145 shRNA#1), the scramble sequence was also designed to construct the stable transfected DU145 cell line(DU145 scramble). Cell migration and invasion were studied using Transwell assay. Quantitative RT-PCR, Western blot (WB) were used to quantify PSCA, E-cadherin, ß-catenin, Vimentin, Fibronectin expression in DU145, DU145 scramble, DU145 shRNA#1 in vitro and in vivo. RT-PCR, immunofluorescent staining were used to quantify PSCA, E-cadherin, and Vimentin expression in vitro. EMT-related genes Snail, Slug, and Twist, were quantified by quantitative RT-PCR in vitro. RESULTS: The constructed stable knockdown of the PSCA in the DU145 cell had a silencing effect up to 90.5 %. DU145 shRNA#1 became scattered from the tightly packed colonies. It was associated with decreased cell migration and invasion. There was also an increased Vimentin and Fibronectin expression, an inhibited E-cadherin and ß-catenin expression at both the mRNA and the protein levels when compared to the DU145 and the DU145 scramble in vitro and vivo. Furthermore, with the exception of the Snail, the expression of EMT-related Slug and Twist genes were upregulated. CONCLUSIONS: Our data indicated that knockdown of PSCA induced EMT and reduced metastatic potentials of the DU145 cells, suggesting that PSCA played an important role in prostatic carcinogenesis and progression.