ABSTRACT
INTRODUCTION: During the last decades, the advent of flexible ureteroscopic lithotripsy has revolutionized the management of upper urinary tract stones. We designed a patented tip-bendable ureteral access sheath to facilitate stone clearance. Our current study reported our initial experience of 224 cases. MATERIALS AND METHODS: The study is a descriptive, retrospective analysis. The initial 224 cases, operated consecutively by one surgeon during 16 months, were reviewed. The novel tip-bendable ureteral access sheath was applied in the procedure. Demographics, laboratory tests, and peri- and postoperative findings (operation duration, stone-free rate (SFR), utilization of flexible instruments and complications) were analyzed. RESUTLS: The median age of the patients was 56 years and the mean stones size was 2.3 ± 1.3 cm. There were 63 cases of upper ureteral stone, 93cases of renal stone and 68 cases of ureteral-renal stones. The mean operative time was 69.2 ± 65.2 min. The immediate stone-free rate was 76.8% and the 1 month post-operative stone-free rate was 97.3%. Most cases(95.5%)were success in single session. Two patient experienced post-operative fever. There was no unplanned readmission. The frequency of post-operative complications was estimated at 0.89% (Clavien I). CONCLUSION: Flexible ureteroscopic lithotripsy with tip-bendable ureteral access sheath is a safe and effective procedure, which can achieve excellent stone clearance.
Subject(s)
Kidney Calculi , Lithotripsy , Ureter , Ureteral Calculi , Humans , Middle Aged , Ureteroscopy/methods , Retrospective Studies , Ureter/surgery , Ureteral Calculi/surgery , Ureteral Calculi/complications , Lithotripsy/methods , Kidney Calculi/surgery , Kidney Calculi/complications , Treatment OutcomeABSTRACT
BACKGROUND: The circulating levels of Cyr61 (also known as CCN1) may prove to have great clinical value in the diagnosis, monitoring and prognosis of many disorders in humans. However, the reference intervals (RIs) for this analyte in human subjects have not previously been well established. Therefore, establishing RIs and determining the distribution of circulating Cyr61 levels are very important for future clinical studies and could provide an orientation value for exploring its clinical usefulness. METHODS: The Cyr61 levels in 2,514 healthy Chinese Han subjects (1,250 males and 1,264 females, aged 18 - 88 years, recruited from 4 hospitals in Shanghai and Fujian) were measured with a sandwich ELISA (R&D Systems, USA). The RIs were determined in a manner consistent with the Clinical and Laboratory Standards Institute guidelines. RESULTS: The levels of serum Cyr61 showed a non-Gaussian distribution. A statistically significant difference was observed between the males and females such that the median level of Cyr61 in the males was significantly higher than that in the females. Furthermore, the Cyr61 levels significantly increased with age in the female group whereas no difference was observed among the different age groups among the males. The RIs for serum Cyr61 were 3.3 - 184 pg/mL and 5.0 - 182 pg/mL in females aged 18 - 45 and 46 - 88 years, respectively. The RI for serum Cyr61 was 4.0 - 198 pg/mL in the males. CONCLUSIONS: The RIs for serum Cyr61 were established among Chinese Han individuals. The effects of age and gender on the distribution characteristics of serum Cyr61 were studied, revealing that the RIs were gender and, in females, age-specific, which may suggest that a female hormone, estrogen plays a role in the regulation of Cyr61 expression in vivo.
Subject(s)
Cysteine-Rich Protein 61 , Adolescent , Adult , Aged , Aged, 80 and over , China , Cysteine-Rich Protein 61/genetics , Female , Healthy Volunteers , Humans , Male , Middle Aged , Prognosis , Reference Values , Young AdultABSTRACT
BACKGROUND: Recent studies have found that inflammatory response is involved in the pathogenesis of ovarian cancer. Advanced ovarian cancer is often presented with ascites that is rich in cytokines, inflammatory factors or cancer cells. Therefore, it is important to study the microenvironment of ascites in order to further clarify the occurrence and progression of ovarian cancer. As a pro-inflammatory factor, the Cyr61 expression patterns are inconsistent in human tumors. Although it has been reported that Cyr61 is related to the progression of ovarian cancer, its specific mechanism is not yet clear. This study sought to evaluate the Cyr61 levels of ascites, serum and different tissues of ovarian cancer to explore the potential association of Cyr61with the tumor-associated inflammatory microenvironment of EOC. METHODS: Tumor specimens were procured from patients with ovarian serous cystadenocarcinoma and ovarian serous cystadenoma. Cyr61 and IL-6 levels of serum or ascites were determined by ELISA (Enzyme-Linked ImmunoSorbent Assay), while Cyr61 expressions of different ovarian tumor tissues were evaluated by IHC (Immunohistochemistry). Then the correlation of Cyr61 level in ascites with clinicopathologic features was analyzed. And other laboratory data were obtained from medical records. RESULTS: Both in ascites and serum, significantly higher Cyr61 levels were found in ovarian serous cystadenocarcinoma. In malignant ascites, higher Cyr61 level of ovarian serous cystadenocarcinoma was more closely associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. And the increased IL-6 level was linearly related to Cyr61 level. Moreover, the serum levels of Cyr61, IL-6 and CRP in advanced stage of ovarian cancer were much higher than those in early stage. Lastly, the IHC data demonstrate that Cyr61 expression of ovarian serous adenocarcinoma was higher than that of ovarian serous cystadenoma, but it was lower than the paired metastatic lesions. CONCLUSIONS: As a pro-inflammatory factor, increased ascites Cyr61 level is associated with FIGO stage, initial tumor size > 10 cm and the residual tumor size. Moreover, serum Cyr61 may be used as a potential marker for EOC inflammatory response. Finally, Cyr61 may be involved in the process of tumor metastasis and progression by producing IL-6 and CRP in the EOC inflammatory microenvironment.
Subject(s)
Biomarkers, Tumor , Carcinoma, Ovarian Epithelial/metabolism , Carcinoma, Ovarian Epithelial/pathology , Cysteine-Rich Protein 61/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Tumor Microenvironment , Adult , Aged , Cell Line, Tumor , Cytokines/metabolism , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression , Humans , Inflammation Mediators/metabolism , Middle Aged , Neoplasm StagingABSTRACT
BACKGROUND: Hospital length of stay (LOS) has recently been receiving increasing attention as a marker of medical resource consumption. Identifying predictors of longer LOS can better equip doctors to counsel patients and facilitate more efficient patient flow and utilization of medical resources. The objective of this study was to identify pre- and intra-operative risk factors for postoperative hospital LOS in patients who had undergone radical prostatectomy in China. METHODS: We retrospectively analyzed data of 793 eligible patients with prostate cancer who had undergone radical prostatectomy in our institution between January 2011 and March 2016. Relevant preoperative variables, including patient characteristics, medical comorbidities, prostate cancer disease-specific variables, urinary tract symptoms, preoperative laboratory values, and intraoperative variables including operation type, operation duration, and blood loss, were analyzed. The outcome was postoperative length of stay which was calculated as the time from the date of operation to the date of discharge. Multiple linear regression analysis was used to identify predictors of this outcome. RESULTS: The mean postoperative LOS was 11.7 days (±4.6 days) and the median 10 days (range, 5-46 days). According to univariate and multivariate analysis, operation type (open or laparoscopic), blood loss, Gleason score (≥8) and preoperative laboratory values of white blood count (WBC) were found to be the main explanatory predictors of postoperative LOS of patients with prostate cancer in our institution. Additionally, open surgery was the strongest significant predictor of longer LOS according to the standardized coefficients in this model. CONCLUSIONS: Our findings indicate that significant predictors of longer postoperative LOS in patients who have undergone radical prostatectomy in China include both preoperative variables of Gleason score, WBC and intraoperative variables of operation type (open or laparoscopic), blood loss. To shorten hospital LOS in patients with prostate cancer and optimize utilization of Chinese medical resources, efforts should be made to improve the intraoperative process and reduce the prevalence of preoperative risk factors.
Subject(s)
Intraoperative Care/trends , Length of Stay/trends , Postoperative Complications/prevention & control , Preoperative Care/trends , Prostatectomy/trends , Prostatic Neoplasms/surgery , Aged , China , Humans , Intraoperative Care/methods , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/epidemiology , Predictive Value of Tests , Preoperative Care/methods , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Retrospective StudiesABSTRACT
PURPOSE: Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro. METHODS: Skin samples from normal donors and psoriasis vulgaris patients were examined the profile of Cyr61 and IL-8 using immunohistochemistry, real-time PCR and Western blotting. HaCaT cells were treated with Cyr61 and IL-8 expression was analyzed by real-time PCR and ELISA. Signal transduction pathways in Cyr61-induced IL-8 production were investigated by real-time PCR, western blotting, luciferase reporter assay or chromatin immunoprecipitation (ChIP) assay. IMQ-induced psoriasis-like mice were treated with anti-Cyr61monoclonal antibodies (mAb), or IgG1 as a control. RESULTS: We found that Cyr61 was abundant in the epidermis of patients with psoriasis vulgaris and positively correlated with the pathogenesis of skin lesions. Cyr61 induced IL-8 production by keratinocytes in a dose dependent manner. This IL-8 synthesis occurred in an IL-1ß- and TNF-α- independent mode via PI3K, AKT and JNK activation, with binding of enhanced AP-1, C/EBPß and NF-κB to sites located in the IL-8 promoter region. Treatment with anti-Cyr61 mAb led to reduction of MIP-2 level, decreased neutrophil infiltration, and attenuated inflammation in vivo. CONCLUSIONS: Our results not only reveal a novel mechanism illustrating the role of Cyr61 in epidermis pathogenesis but also suggest that therapies targeting Cyr61 may represent a novel strategy in the treatment of psoriasis vulgaris.
Subject(s)
Cysteine-Rich Protein 61/immunology , Interleukin-8/immunology , Psoriasis/immunology , Adult , Animals , Cell Line , Cysteine-Rich Protein 61/genetics , Female , Humans , Interleukin-1beta/genetics , Interleukin-8/genetics , Keratinocytes/immunology , MAP Kinase Signaling System/immunology , Male , Mice, Inbred BALB C , Middle Aged , NF-kappa B/immunology , Psoriasis/pathology , RNA, Small Interfering/genetics , Skin/immunology , Skin/pathology , Tumor Necrosis Factor-alpha/genetics , Young AdultABSTRACT
OBJECTIVES: The aim of this study was to investigate the effect and potential mechanism of Cysteine-rich 61 (Cyr61) on stimulating MMP-3 expression by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: Primarily cultured RA FLS were treated with exogenous Cyr61 protein or Cyr61-siRNA, then, MMP-3 expression was analyzed by real-time PCR, western blotting and ELISA. Signal transduction pathways in Cyr61-induced MMP-3 production were examined by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay. Mice with collagen-induced arthritis (CIA) were treated with anti-Cyr61 monoclonal antibodies (mAb), or IgG1 as control and MMP-3 in the joint was detected by IHC, real-time PCR and western blotting. RESULTS: High expressed MMP-3 and Cyr61 were positively correlated in RA ST; Cyr61 stimulated MMP-3 production in FLS of RA patients in an IL-1ß and TNF-α independent manner. Cyr61 induced MMP-3 could further enhance the invasive ability of RA FLS. Mechanistically, we found that Cyr61 promoted MMP-3 production via the P38, JNK-dependent AP-1 signaling pathway. Blockage of Cyr61 function with monoclonal antibody could decrease MMP-3 expression in the joints of CIA mice. CONCLUSION: This study provides new evidence that Cyr61 participates in RA pathogenesis not only as a pro-inflammatory factor but also plays a key role in bone erosion via promoting MMP-3 expression. We suggest that targeting of Cyr61 may represent a potential strategy in RA treatment.
Subject(s)
Arthritis, Rheumatoid/metabolism , Cysteine-Rich Protein 61/metabolism , Matrix Metalloproteinase 3/genetics , Synoviocytes/metabolism , Animals , Cells, Cultured , Cysteine-Rich Protein 61/genetics , Cysteine-Rich Protein 61/pharmacology , Humans , Interleukin-1beta/metabolism , MAP Kinase Signaling System , Male , Matrix Metalloproteinase 3/metabolism , Mice , Synoviocytes/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
It has been widely accepted that macrophages are divided into M1 "pro-inflammatory" macrophages and M2 "anti-inflammatory" macrophages and an uncontrolled macrophage polarization plays an important role in the pathogenesis of different diseases. As the main substance of total glucosides of peony, paeoniflorin (PF), has been widely used to treat autoimmune and autoinflammatory diseases for years. Mechanistically, PF has been found to alter activities of many immune cells, which could further reduce inflammation and tissue damage. However, whether and how PF affects macrophages activities in vitro remains unknown. In current study, using M1 and M2 cells generated from mouse bone marrow precursors, we explored the role of PF in regulating M1/M2 cells activity in vitro. The results showed that PF inhibited LPS-induced M1 activity by reducing iNOS expression and NO production via decreasing LPS/NF-κB signaling pathway; whereas, PF enhanced IL-4-provoked M2 function by up-regulating Arg-1 production and activity via increasing IL-4/STAT6 signaling pathway. Our new finding indicates that PF can suppress M1 cells activity and enhance M2 cells function simultaneously, which could help to ameliorate autoimmune and autoinflammatory diseases in clinical treatment.
Subject(s)
Glucosides/pharmacology , Immunomodulation , Macrophage Activation/drug effects , Macrophages/immunology , Monoterpenes/pharmacology , Animals , Arginase , Autoimmune Diseases/drug therapy , Cell Polarity/drug effects , Cells, Cultured , Glucosides/therapeutic use , Interleukin-4 , Lipopolysaccharides/antagonists & inhibitors , Macrophages/classification , Male , Mice, Inbred BALB C , Monoterpenes/therapeutic use , NF-kappa B , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Phytotherapy , STAT6 Transcription Factor , Signal Transduction/drug effectsABSTRACT
Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process.
ABSTRACT
IL-1ß plays a major role in the development of rheumatoid arthritis (RA). We previously showed that Cyr61 participates in RA pathogenesis as a proinflammatory factor. Here, we found that the levels of IL-1ß and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1ß mRNA and proIL-1ß protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1ß was hardly detectable in the supernatant. We also found that the level of adenosine triphosphate (ATP) in SF and ST was significantly increased in RA patients and that the level of IL-1ß in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1ß production in FLS via the AKT-dependent NF-κB signaling pathway, and ATP caused Cyr61-induced proIL-1ß to generate IL-1ß in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1ß production in FLS.
Subject(s)
Arthritis, Rheumatoid/genetics , Cysteine-Rich Protein 61/genetics , Fibroblasts/metabolism , Interleukin-1beta/genetics , RNA, Messenger/metabolism , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Caspase 1/metabolism , Cysteine-Rich Protein 61/metabolism , Female , Humans , Interleukin-1beta/metabolism , Male , Middle Aged , NF-kappa B/metabolism , Osteoarthritis/genetics , Osteoarthritis/metabolism , Promoter Regions, Genetic , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Synovial Fluid/metabolism , Synovial Membrane/cytologyABSTRACT
B cells are important in the development of autoimmune disorders through mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and targeting which reduces inflammation and tissue damage effectively but often leads to patients suffering from secondary infection. Paeoniflorin (PF) is the main substance of the Total glucosides of peony and has been widely used to treat autoimmune diseases for years. However, whether PF affects B cell activity remains unknown. In this study, using purified murine spleen B cells, we analyzed the effects of PF on B-cell function in vitro. We found that PF inhibited the expression of CD69/CD86 and the proliferation of B cells stimulated by LPS. In addition, PF reduced the B-cell differentiation and immunoglobulin production that was stimulated by LPS. Interestingly, PF did not alter B-cell activation and proliferation provoked by anti-CD40 or IL-4. These results indicated for the first time that PF inhibits B-cell activation, proliferation and differentiation by selectively blocking the LPS/TLR4 signaling pathway. Furthermore, our data suggest that PF selectively inhibits inflammation and tissue damage mediated by LPS-activated B cells but does not alter CD40/CD40L- or IL-4-provoked B-cell function in autoimmune diseases treatment, which might aid in protecting patients from secondary infection.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , B-Lymphocytes/immunology , Cell Proliferation/drug effects , Glucosides/pharmacology , Lymphocyte Activation/drug effects , Monoterpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Bipolar Disorder , Cell Differentiation/drug effects , Cells, Cultured , Female , Glucosides/therapeutic use , Immunoglobulins/metabolism , Lipopolysaccharides/adverse effects , Mice, Inbred C57BL , Monoterpenes/therapeutic use , Phytotherapy , Signal Transduction/drug effects , Spleen/cytology , Toll-Like Receptor 4ABSTRACT
OBJECTIVE: To explore the diagnosis, treatment, and prognosis of prostatic malignant mesenchymal tumors (PMMT). METHODS: We retrospectively analyzed the clinical and follow-up data about 20 cases of PMMT and reviewed the literature relevant to the diagnosis, treatment, and prognosis of the disease. RESULTS: Based on the results of pathology and immunohistochemistry, the 20 PMMT cases included leiomyosarcoma (n = 7), rhabdomyosarcoma (n = 5), prostatic stromal sarcoma (n = 3), chondrosarcoma (n = 1), and undifferentiated PMMT (n = 4). Twelve of the patients were treated by radical prostatectomy (3 concurrently by sigmoid colostomy and 1 by cystostomy), 2 by pelvic tumor resection following arterial embolization, 1 by total pelvic exenteration, 1 by colostomy with pelvic lymph node biopsy, and 4 by conservative therapy because of metastasis to the lung, pelvis and bone. Of the 20 patients, 9 died of systemic metastasis within 3 months after treatment, 3 died at 6, 7, and 14 months, respectively, 3 survived with tumor for 5, 11, and 12 months, respectively, 2 survived without tumor for 12 and 24 months so far, all subjected to periodic chemotherapy postoperatively, and 3 lost to follow-up. CONCLUSION: PMMT is a tumor of high malignancy and rapid progression, for which transrectal ultrasound-guided biopsy remains the main diagnostic method. The clinical stage of the tumor is an important factor influencing its prognosis and the survival rate of the patients can be improved by early diagnosis and combined therapy dominated by radical prostatectomy.
Subject(s)
Mesenchymoma/pathology , Mesenchymoma/therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Combined Modality Therapy/methods , Humans , Immunohistochemistry , Male , Mesenchymoma/mortality , Prognosis , Prostatectomy , Prostatic Neoplasms/mortality , Retrospective StudiesABSTRACT
OBJECTIVE: To translate the English version of The Premature Ejaculation Diagnostic Tool (PEDT) into Chinese, evaluate its reliability and validity, and analyze its feasibility in the diagnosis of premature ejaculation (PE). METHODS: Following the forward-backward translation procedure, we developed the Chinese version of PEDT, which was then revised by andrologists and bilingual linguists. We enrolled subjects with or without PE from 15 urological or andrological clinics in China and obtained the information about their demographic characteristics, PEDT scores, and intra-vaginal ejaculation latency time (IELT). We evaluated the internal consistency of PEDT using Cronbach alpha, was examined its reliability and stability by test-retest analysis, analyzed its correlation with IELT by Spearman correlation analysis, and tested its sensitivity and specificity by receiver operating characteristic ( ROC) analysis. RESULTS: Totally, 570 PE patients (aged [30.66 ± 7.11] years) and 226 non-PE men (aged [33.01 ± 5.41] years) were recruited, with the mean IELT of (1.34 ± 0.54) min in the former and (11.09 ± 7.5) min in the latter group. The Cronbach's alpha of the Chinese version of PEDT was 0.79, and the test-retest correlation coefficient was 0.75 (P < 0.01). The PEDT score was negatively correlated with IELT (Spearman's p = -0.52, P < 0.01). When the cutoff value of PE diagnosis was defined as 7.5, the sensitivity and specificity of PEDT were 0.80 and 0.78, and when as 8.5, they were 0.72 and 0.89, respectively. CONCLUSION: The Chinese version of PEDT was demonstrated to have good internal consistency, reliability, and validity, as well as a high predictability for PE. It can be used as a reliable and convenient tool to screen PE among Chinese men.
Subject(s)
Premature Ejaculation/diagnosis , Translations , Adult , Aged , Asian People , China , Ejaculation , Feasibility Studies , Humans , Language , Male , Middle Aged , ROC Curve , Reaction Time , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvß5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.
Subject(s)
Arthritis, Rheumatoid/immunology , Cell Differentiation/immunology , Cysteine-Rich Protein 61/physiology , Fibroblasts/immunology , Interleukin-6/biosynthesis , Synovial Membrane/immunology , Th17 Cells/immunology , Adult , Aged , Animals , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Cells, Cultured , Coculture Techniques , Female , Fibroblasts/metabolism , Fibroblasts/pathology , Humans , Interleukin-6/physiology , Male , Mice , Mice, Inbred DBA , Middle Aged , Receptors, Vitronectin/physiology , Signal Transduction/immunology , Synovial Membrane/metabolism , Synovial Membrane/pathology , Th17 Cells/pathologyABSTRACT
OBJECTIVE: To evaluate the clinical values of computed tomography angiography (CTA) for severe hemorrhage after percutaneous nephrolithotomy (PCNL). METHODS: A total of 50 patients with bleeding after PCNL were enrolled. All patients underwent renal artery CTA. There were 34 males and 16 females with an average age of 45.7 years. Left (n = 31) and right (n = 19) sides were affected. The criteria of severe bleeding included a one-off amount of bleeding over 400 ml after PCNL or/and hemoglobin decreased 20 g/L after PCNL. RESULTS: Among them, CTA showed pseudoaneurysm (n = 24), arteriovenous fistula (n = 6), suspicious bleeding spot (n = 4) and no obvious bleeding spot (n = 16). And 24 pseudoaneurysm and 6 arterovenous fistula patients underwent digital subtraction angiography (DSA) immediately. The bleeding spots were successfully intervened and coil embolization treatment was performed. Three of 4 suspicious bleeding cases had rebleeding mini-pseudoaneurysms. The remaining one case of rebleeding was successfully controlled by conservative measures. CONCLUSION: Renal artery CTA is the first-line screening technique for severe bleeding after PCNL. But for arterial hemorrhage patients, DSA examination may be directly conducted.
Subject(s)
Hemorrhage , Nephrostomy, Percutaneous/adverse effects , Renal Artery , Aneurysm, False , Angiography, Digital Subtraction , Arteriovenous Fistula , Female , Humans , Male , Middle AgedABSTRACT
A 51-year-old woman was found to have a left renal calculus with hydronephrosis. She underwent unsuccessful extracorporeal shock wave lithotripsy, leading to the recommendation that percutaneous lithotomy was necessary to remove the renal calculus. In view of the unusual shape of the calculus and absence of abnormalities in urine sediment, preoperative computed tomography and renal angiography were performed, which instead showed a calcified left renal artery aneurysm. Subsequent efforts to perform an aneurysmectomy also failed, eventually necessitating left nephrectomy. This case illustrates the pitfalls in the diagnosis of a renal artery aneurysm, which is a relatively common condition that may have unusual presentations. Hence, it is suggested that the possibility of a renal artery aneurysm be considered in the differential diagnosis when one detects a renal calculus with an unusual appearance. In addition, we propose that 3-dimensional reconstruction computed tomography be performed before considering surgical options for such renal calculi to rule out the possibility of a renal artery aneurysm.
Subject(s)
Aneurysm/diagnosis , Hydronephrosis/diagnosis , Kidney Calculi/diagnosis , Renal Artery , Vascular Calcification/diagnosis , Diagnosis, Differential , Female , Humans , Middle AgedABSTRACT
BACKGROUND: Percutaneous nephrostolithotomy is important approach for kidney stones removal. A percutaneous nephrostomy drainage tube placement is an effective method to stop venous bleeding. Occasionally, the catheter can pierce into the renal parenchyma, and migrate into the renal vein even to the vena cava. CASE PRESENTATION: A 66-year-old woman underwent a percutaneous nephrostolithotomy for kidney staghorn stone complicating severe bleeding. A computed tomography angiography showed the percutaneous nephrostomy drainage tube inside the renal vein. The percutaneous nephrostomy drainage tube was withdrawn 3 cm back to the renal parenchyma/sinus/pelvis in stages with the surgical team on standby. Seven days later, the patient developed severe hematuria. Computed tomography angiography demonstrated the pseudoaneurysm located near the percutaneous nephrostomy drainage tube. Pseudoaneurysm is embolized successfully. CONCLUSION: Our case shows intravenous misplacement of the nephrostomy tube and subsequent pseudoaneurysm after percutaneous nephrostolithotomy. To our knowledge, this seems to be the first documentation of major bleeding from the injury to both renal vein and artery. The percutaneous nephrostomy drainage tube can be withdrawn back to the renal parenchyma/sinus/pelvis in stages with the surgical team on standby, and the withdrawn distance may vary according to patient and catheter position.
Subject(s)
Aneurysm, False/etiology , Aneurysm, False/therapy , Nephrostomy, Percutaneous/adverse effects , Renal Artery/injuries , Renal Artery/surgery , Renal Veins/injuries , Renal Veins/surgery , Aged , Aneurysm, False/diagnosis , Female , Humans , Radiography , Renal Artery/diagnostic imaging , Renal Veins/diagnostic imaging , Treatment OutcomeABSTRACT
OBJECTIVE: To report the incidence, risk factors, and treatments of renal subcapsular hemorrhage (RSH) complicating ureteroscopic lithotripsy (URSL). PATIENTS AND METHODS: Data from 1,918 URSLs performed between January 2004 and March 2012 were retrospectively analyzed. Patients' data included age, sex, relevant medical history, stone side, size, and degree of hydronephrosis. RESULTS: All 8 patients were identified as having an RSH after URSL. There were 2 males and 6 females with a mean age of 45.6 years (range 30-62 years). The patients' relevant medical histories (renal calculi extracorporeal shock wave lithotripsy, renal operation and hypertension) were statistically different between those who did and did not develop an RSH. Acute onset of flank pain is the most common symptom. Three patients with infective and large hemorrhage were managed by percutaneous nephrostomy in 1 and percutaneous subcapsular drainage in 2. Five patients with small and uninfected hemorrhage were managed conservatively. CONCLUSIONS: The rate of development of RSH complicating URSL is very low. RSH complicating URSL can occur in patients with underlying renal abnormalities. RSH is rarely associated with abrupt hemodynamic instability and usually not lethal. Treatment is selected based on the patient's hemodynamic state, infection, renal function, and the feasibility of treatment modality.
Subject(s)
Hemorrhage/etiology , Kidney/blood supply , Lithotripsy , Ureteral Calculi/surgery , Ureteral Calculi/therapy , Ureteroscopy/adverse effects , Adult , Contrast Media , Endoscopy , Female , Hemodynamics , Hemorrhage/epidemiology , Humans , Hydronephrosis/surgery , Hypertension/complications , Incidence , Kidney/surgery , Kidney Calculi/surgery , Lasers , Male , Middle Aged , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Psoriasis is a chronic skin disorder characterized by epidermal keratinocyte hyperproliferation and inflammatory infiltration. CCN1 (also termed CYR61 or cysteine-rich angiogenic inducer 61) is an extracellular matrix-associated protein that is involved in multiple physiological functions. In psoriasis, we recently demonstrated that the overexpression of CCN1 promoted keratinocyte proliferation and activation. Furthermore, CCN1 was highly expressed in psoriatic skin lesions from psoriasis vulgaris patients. Here, we dissect the underlying molecular mechanism in imiquimod (IMQ) and interleukin (IL)-23-induced psoriasis-like models. Our results demonstrate that CCN1 can significantly upregulate IL-36 production in the murine skin of IMQ and IL-23-induced psoriasis-like models. Injection of CCN1-neutralizing antibody improved epidermal acanthosis and significantly reduced IL-36 production in vivo. These results suggest that CCN1 can be a critical upstream pro-inflammatory factor in psoriasis. In primary normal human epidermal keratinocytes, we demonstrated that CCN1 can selectively induced the production of IL-36α and IL-36γ through the activation of the protein kinase B (AKT)/nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and extracellular-regulated kinase (ERK)/CCAAT/enhancer binding protein ß (CEBPß) signaling pathways via integrin receptor α6ß1 in vitro. Our results suggest that targeting CCN1 can be a potential therapeutic strategy for psoriasis.
Subject(s)
NF-kappa B , Psoriasis , Humans , Animals , Mice , NF-kappa B/metabolism , NF-kappa B/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Skin/pathology , Keratinocytes/metabolism , Imiquimod/adverse effects , Disease Models, Animal , Mice, Inbred BALB CABSTRACT
Cysteine-rich protein 61(CCN1/Cyr61) has been implicated as an important mediator in proliferation and metastasis of breast cancer, which indicated that blockage of Cyr61 might be a potent target for breast cancer treatment. However, the antitumor effect of anti-Cyr61 antibodies on breast cancer in vivo has not been reported so far. In this study, we reported the effect and likely mechanism of generated anti-human Cyr61 monoclonal antibodies (mAb) on Cyr61 high expression line MDA-MB-231, known as a highly malignant and invasive human breast cancer cell line, at aspects of proliferation and migration in vitro and in vivo. We found the mAb, denoted as 093G9, revealed inhibitory effects on MDA-MB-231 cell proliferation, migration, and invasion through downregulation of both AKT and ERK phosphorylation in vitro compared with its isotype control. 093G9 also showed significant efficacy on suppressing primary tumor growth and spontaneous lymph node metastasis in in vivo mouse model. The specific epitope recognized by 093G9 was identified to be (140)LPNLGCP(146), adjacent to the VWC domain of Cyr61 by Ph.D.-C7C phage library display system. Our study provides direct evidence that Cyr61 can be a potent therapeutic target for patients who bear high Cyr61 expression breast cancer. Furthermore, the mAb, 093G9 developed in our laboratory, has shown a promising therapeutic characteristic in breast cancer.
Subject(s)
Antibodies, Monoclonal/pharmacology , Breast Neoplasms/immunology , Breast Neoplasms/therapy , Cysteine-Rich Protein 61/antagonists & inhibitors , Cysteine-Rich Protein 61/immunology , Animals , Antibodies, Monoclonal/immunology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/immunology , Cell Proliferation , Cysteine-Rich Protein 61/genetics , Down-Regulation , Epitopes/immunology , Extracellular Signal-Regulated MAP Kinases/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Humans , Lymphatic Metastasis , Mice , Mice, Inbred BALB C , Neoplasm Invasiveness , Phosphorylation , Proto-Oncogene Proteins c-akt/immunology , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Total glucoside of paeony (TGP), an active compound extracted from paeony root, has been used in therapy for rheumatoid arthritis (RA). Th1 and Th17 cells are now believed to play crucial roles in the lesions of RA. However, the molecular mechanism of TGP in inhibition of Th1 and Th17 cells remains unclear. In this study, we found that TGP treatment significantly decreased percentage and number of Th1 and Th17 cells in collagen induced arthritis (CIA) mice. Consistently, treatment with TGP decreased expression of T-bet and RORγt as well as phosphorylation of STAT1 and STAT3. In particular, TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of IL-12 and IL-6. Moreover, TGP-treatment RA patients showed shank population of matured DCs and IFN-γ-, IL-17-producing cells. Taken together, our results demonstrated that TGP inhibited maturation and activation of DCs, which led to impaired Th1 and Th17 differentiation in vivo.