Bladder cancer is one of the common tumors of urinary system. Early detection and treatment can reduce the recurrence rate and mortality. Currently, it is difficult to balance the diagnostic specificity and sensitivity of traditional diagnostic methods. However, Raman spectroscopy, as a molecular diagnostic technology, can reveal the difference between normal urinary tract epithelial tissue and urinary tract epithelial cell carcinoma of the bladder at the molecular level, which has the characteristics of faster and more accurate diagnosis compared with traditional diagnostic techniques. This paper reviews the research progress of Raman spectroscopy in the diagnosis of bladder cancer.
Background Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. Methods This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. Results The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. Conclusions Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.
目的 探讨鹅去氧胆酸(CDCA)对雄激素非依赖性前列腺癌细胞生物学特性的影响及可能机制.方法 CDCA作用于雄激素非依赖前列腺癌细胞DU145后,通过油红染色检测细胞内脂肪含量变化,观察CDCA对前列腺癌细胞内脂类的影响;采用CCK8方法测定细胞增殖,采用Real-time PCR及Western blot检测细胞脂类代谢关键因子FASN及ACC的表达.结果 CDCA能够降低DU145细胞内脂质水平,对正常前列腺细胞RWPE-1无明显作用.CDCA作用后,DU145增殖水平明显下降,且随着作用时间延长,抑制作用更显著.Real-time PCR结果显示CD-CA能够抑制FASN及ACC基因的表达水平,同时FASN的蛋白表达水平及ACC磷酸化水平在CDCA作用后均有不同程度的降低.结论 CDCA能够影响DU145细胞增殖,同时对细胞内脂类的合成有明显的抑制作用,其效应机制可能与调节脂类合成酶的表达有关.
Background: The tumor microenvironment (TME) has recently been proven to play a crucial role in the development and prognosis of tumors. However, the current knowledge on the potential of the TME in prostate cancer (PCa) remains scarce. Purpose: This study aims to elucidate the value of TME-related genes for PCa prognosis by integrative bioinformatics analysis. Materials and Methods: We downloaded the immune and stromal scores of PCa samples via the ESTIMATE and correlated these scores to clinicopathological characteristics and recurrence-free survival (RFS) of patients. Based on these scores, the TME-related differentially expressed genes were identified for functional enrichment analysis. Cox regression analyses were performed to identify prognostic genes and establish a predictive risk model. Moreover, gene set enrichment analysis (GSEA) was performed to evaluate the relationship between risk score and immune pathway. Results: The stromal and immune scores were associated with clinicopathological characteristics and RFS in PCa patients. In total, 238 intersecting differentially expressed genes were identified. Functional enrichment analysis further revealed that these genes dramatically participated in the immune-related pathways. The immune-related risk model was built with C-type lectin domain containing 7A (CLEC7A) and collagen type XI alpha 1 chain (COL11A1) using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of CLEC7A and COL11A1 were significantly associated with the RFS. Further, the RFS time in high-risk group was significantly shorter than that in low-risk group. The areas under the curve for the risk model in predicting 3- and 5-year RFS rates were 0.694 and 0.731, respectively. GSEA suggested that immunosuppression existed in high-risk PCa patients. Conclusion: CLEC7A and COL11A1 were selected to build a predictive risk model, which may help clinicians to assess the prognosis of PCa patients and select appropriate targets for immunotherapy.
本综述介绍了当前国内外对CD47在同种异体器官移植中的研究成果,着重从移植物缺血再灌注损伤中的作用和在移植免疫反应中的作用两个方面对不同信号通路的影响进行总结,以期为相关领域的研究人员提供参考。
A parapelvic cyst in the renal sinus is a type of renal cystic disease, and its incidence is extremely low, accounting for about 5% of renal cystic diseases. A normal parapelvic cyst is not difficult to diagnose with imaging examination. However, when the cyst is accompanied by infection or bleeding, it is difficult to distinguish it from renal pelvic carcinoma or cystic renal cell carcinoma in the renal sinus, and it is easily misdiagnosed and can even lead to excessive treatment. This case reports a patient with a parapelvic cyst in the left renal sinus area, in which there was an old hemorrhage and infection. The patient was misdiagnosed with renal pelvic carcinoma preoperatively, and radical nephrectomy was performed. However, the postoperative pathological diagnosis was a parapelvic cyst. Although the renal function of the patient is normal after surgery, it is still impossible to deny that the preoperative misdiagnosis leads to excessive treatment.
随着腹腔镜手术的日益成熟,传统的开放活体供肾切取术( open-living donor nephrectomy,ODN)已经逐渐被腹腔镜活体供肾切取术( Laparoscopic-living donor nephrectomy,LDN)所取代[1].与 ODN相比,LDN创伤小、恢复快,已成为活体供肾切取的首选方法[2].由于右肾静脉较短,肾蒂血管的暴露相比左肾难度更大、危险性更高,故而大多数移植中心主要选择切取左肾,但在临床工作中也常遇到切取右肾更合理的情况.2010年6月至2017年12月,吉林大学第一医院应用后腹腔镜技术结合开放取肾通道成功实施 365 例活体供肾切取术,其中左肾284例,右肾81 例.本研究回顾性分析81 例右侧活体供肾切取术供、受者临床资料,探讨后腹腔镜右侧活体供肾切取术的安全性和有效性.
Background: The aim of this study was to investigate the efficacy and safety of right retroperitoneal laparoscopic live donor nephrectomy (LDN) in 81 cases of living-related renal transplant. Material/Methods: We retrospectively reviewed all living-related donors who underwent right retroperitoneoscopic living donor nephrectomy between June 2010 and December 2017 at the First Hospital of Jilin University and their corresponding recipients. Demographic and clinical data were collected from the hospital's electronic clinical data system. Data on preoperative renal retention parameters, operative time, and donor kidney warm ischemia time, the trimmed length of the renal artery and vein of donor kidney, and the time to extubation were recorded. Complications in both donors and recipients were recorded. Results: We included 81 donors who underwent successful right-sided retroperitoneoscopic LDN, with 31 males and 50 females and a mean age of 47.1 years (range 21-63 years). There was no intraoperative conversion to open donor nephrectomy. The mean operative time was 120.68 +/- 29.8 min. The mean warm ischemic time was 49.26 +/- 3.86 s. The estimate blood loss was 54.32 mL (range 50-400 ml). The median length of hospital stay was 7 days (range 4-13 days). There was neither intraoperative complication such as hemorrhage or lymph fistula nor kidney graft injury. There was no graft renal vein thrombosis and ureteral stricture or other complications. No graft rejection occurred. Conclusions: Right retroperitoneal laparoscopic live donor nephrectomy is safe and effective for renal transplant in living- related renal transplant by laparoscopic excision and extraction of the right kidney with vena cava flap.
Objective:To investigate the risk factors of delayed graft function (DGF) in organ donors after a citizen's death and establish a donor scoring system.Methods:From November 2016 to March 2018, the clinical data of 1 875 donors and 3 549 recipients who performed renal transplantation from deceased donor in 29 transplant centers across the country were collected. Single factor analysis was used to determine the donor risk factors of DGF, and then incorporate multi-factor analysis, calculate the regression coefficient (β value) to establish a DGF risk donor score table.Results:Univariate analysis showed that donor age, primary disease, history of hypertension, serum creatinine level before donation, hypotension and duration of CPR are risk factors for DGF after kidney transplantation, and DGF can be increased to varying degrees incidence rate. A logistic regression model was used to establish a DGF risk donor score table based on the above six risk factors with a total score of 49. As the donor score increased from 0 to 49, the incidence of DGF after renal transplantation increased from 9.96% to 92%.Conclusions:The study has determined the risk factors of DGF donors after renal transplantation from decease donor, and established a scoring system for predicting DGF risk donors in line with the characteristics of the Chinese population, which is helpful for clinicians to evaluation of deceased donor and guiding treatment after renal transplantation.
第14届移植病理Banff会议2017年3月27—31日在西班牙巴塞罗那举行,来自23个国家的479名专家参会,会议内容发表于2018年1月美国移植杂志(Am J Transplant)[1].本次会议:① 对肾移植排斥病理诊断有新修订;② 继续按2015年Banff会议规划探讨有可能纳入Banff分类方案的"分子诊断"[2],包括在抗体介导排斥反应的诊断中,潜在"抗供体特异性抗体(donor specific antibody,DSA)"的替代分子及其分子特性;③ 正式会议前一天的会前会,主要讨论新一代临床试验的终点或替代终点的界定;④ 本次会议照例有不同的Banff工作组(BWG)继续有计划的进行有针对性研究.
目的:探讨沉默调节蛋白1(SIRT1)在膀胱癌组织中的表达情况及在肿瘤进展、侵袭、转移中的作用.方法:选取82例不同病理分期的膀胱尿路上皮癌患者术后石蜡标本,采用免疫组织化学技术检测癌组织及癌旁正常组织中SIRT1的表达,分析其与临床病理特征的关系.另选取15例膀胱尿路上皮癌行膀胱根治术患者的癌组织和癌旁组织,应用Real-Time PCR技术检测SIRT1 mRNA表达水平.结果:SIRT1的表达水平与临床分期、病理分级及是否转移呈相关性(P<0.05),与性别、年龄、是否复发无相关性(P>0.05).癌组织中SIRT1 mRNA的表达明显高于癌旁组织的表达,差异有统计学意义(P<0.05).结论:SIRT1在膀胱癌组织呈高表达,与临床分期及转移相关,有可能作为肿瘤进展的潜在标志物及治疗靶点.
既往针对实体器官移植领域的B淋巴细胞研究主要集中于适应性免疫方面.有关固有B淋巴细胞及自然抗体在实体器官移植中作用的研究则刚兴起.本综述将总结与器官移植致敏及移植排斥反应相关却常被忽视的固有B淋巴细胞免疫的最新研究,并探讨自然抗体在移植受者血清反应性评估中的意义.
移植物的免疫耐受是器官移植领域的最终目标.尽管在小鼠器官移植中报道了诸多诱导免疫耐受的方案,但迄今为止,基于造血干细胞移植的嵌合体方案是人类肾移植中诱导免疫耐受的唯一可重复性方案.通过短暂的混合嵌合或稳定的完全嵌合均可诱导移植肾免疫耐受.尽管持久的完全嵌合状态可能会降低移植肾发生排斥反应的风险,但移植物抗宿主病(graft-versus-host disease,GVHD)的出现限制了此方案的广泛临床应用.相反,短暂的混合嵌合不会导致GVHD的发生,但造血干细胞嵌合消失后很难预测移植物排斥反应的风险.目前的努力旨在开发临床上更可行和可靠的方法来诱导持久的混合嵌合体,以便扩大这些治疗方案的临床适用性.
Background/Aim: Glioma is a deadly form of brain cancer. Doxorubicin is cytotoxic against glioma cells. However, the blood-brain barrier (BBB) limits its ability to be delivered to the brain. Materials and Methods: Liposomes (R8PLP) formed from, 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (PEG-DSPE), cholesterol and egg phosphatidylcholine (ePC) were modified by cell-penetrating peptide R8 conjugated with oleic acid as a novel method for delivering doxorubicin. The antitumor effect of R8PLP was evaluated by uptake, cytotoxicity and brain accumulation. Results: The size of R8PLP was 95 nm. Doxorubicin was loaded into R8PLP by active loading with more than 95% encapsulation efficiency. Cellular uptake of R8PLP by U87-MG cells was 8.6-fold higher than that of unmodified liposomes. R8PLP reduced cell viability by 16.18% and 18.11% compared to cholesterol-ePC-liposomes and free doxorubicin, respectively, at 3.6 mu M after 24 h treatment. The biodistribution of doxorubicin in the brain was significantly improved by R8PLP. The area under the concentration-time curve (AUC(0.5-12 h)) of R8PLP was 2.4-times higher than that of cholesterol-ePC-PEG-DSPE-liposomes. Conclusion: These results suggest that R8-conjugated oleic acid-modified liposomes are effective delivery vehicles for glioma.
Primary hyperoxaluria type 2 is a rare autosomal recessive disorder caused by glyoxylate reductase/hydroxypyruvate reductase deficiency and characterized by recurrent episodes of nephrolithiasis and nephrocalcinosis. Herein, we describe a case of primary hyperoxaluria type 2 in a 33-year-old man who failed to respond to conventional therapies; thus renal transplantation was performed. This case demonstrated that, although primary hyperoxaluria type 2 is rare, hyperoxaluria should be suspected and blood oxalate and stone component be examined in patients with recurrent episodes of nephrolithiasis, particularly in those who are unresponsive to conventional therapies. Combined liver-kidney transplant may be required as kidney transplant alone is not likely to be successful.
CD47 is a ubiquitously expressed transmembrane glycoprotein that plays a complex role in regulation of cell survival and function. We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of cellular xenografts by macrophages. However, the role of CD47 in solid organ transplantation remains undetermined. Here, we explored this question in mouse models of heart allotransplantation. We observed that the lack of CD47 in donor hearts had no deleterious effect on graft survival in syngeneic or single MHC class I-mismatched recipients, in which both wild-type (WT) and CD47 knockout (CD47 KO) mouse hearts survived long term with no sign of rejection. Paradoxically, elimination of donor CD47 was beneficial for graft survival in signal MHC class II- and class I- plus class II-mismatched combinations, in which CD47 KO donor hearts showed significantly improved survival compared to WT donor hearts. Similarly, CD47 KO donor hearts were more resistant than WT hearts to humoral rejection in α1,3-galactosyltransferase-deficient mice. Moreover, a significant prolongation of WT allografts was observed in recipient mice treated with antibodies against a CD47 ligand thrombospondin-1 (TSP1) or with TSP1 deficiency, indicating that TSP1-CD47 signaling may stimulate vascularized allograft rejection. Thus, unlike cellular transplantation, donor CD47 expression may accelerate the rejection of vascularized allografts.
The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN).
目的:探讨不同CYP3A5基因型对肾移植术后患者=血他克莫司浓度的影响,为肾移植术后患者他克莫司个体化治疗提供依据.方法:回顾性分析115例肾移植术后患者的临床资料,根据CYP3A5基因型分为野生纯合子组(CYP3A5*1/*1型,11例)、突变杂合子组(CYP3A5*1/*3型,46例)和突变纯合子组(CYP3A5* 3/*3型,58例),记录3组患者术后不同时间点(7d、1个月、3个月、6个月、1年和2年)有效的血他克莫司浓度/剂量(C0/D)值.结果:3组患者体质量指数(BMI)、年龄构成比和性别构成比比较差异均无统计学意义(P>0.05).与突变杂合子组比较,野生纯合子组患者术后7d、3个月、1年和2年他克莫司C0/D值明显降低(P=0.011,P<0.01,P=0.022,P=0.024);与突变纯合子组比较,野生纯合子组和突变杂合子组患者术后各个时段他克莫司C0/D值均明显降低(P<0.01).野生纯合子组术后7d患者他克莫司C0/D值明显低于术后6个月、1年和2年(P=0.004,P=0.049,P=0.036);突变杂合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.006,P<0.01,P<0.01,P<0.01,P<0.01),术后1个月患者他克莫司C0/D值明显低于术后6个月(P=0.013);突变纯合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.002,P<0.01,P<0.01,P<0.01,P<0.01).结论:CYP3A5基因多态性对肾移植术后患者血他克莫司浓度有明显影响,且这种影响可持续至术后2年.
肾移植术后产生的抗体与移植肾排斥反应密切相关,并影响移植肾长期存活.近年来非HLA抗体在肾移植领域越来越受到关注.尽管对非HLA抗体的研究并不全面,然而实验及临床研究均发现针对某些非HLA抗原诸如血管紧张素1类受体、基底膜聚糖、自身抗原等产生的抗体能够影响移植肾急性及慢性排斥反应的进程.非HLA抗体影响移植肾排斥反应及存活的潜在机制是目前研究的重要领域之一.本文针对肾移植领域主要的非HLA抗体做一综述,并阐述其对移植物的致病机制.鉴别出非HLA介导的移植肾抗体性排斥反应的免疫表型,有利于为治疗移植肾抗体性排斥反应提供新的靶点,并为提高移植物的长期存活提供有效策略.
Hyperglycemia-induced renal fibrosis causes end-stage renal disease. Clopidogrel, a platelet inhibitor, is often administered to decrease cardiovascular events in diabetic patients. We investigated whether clopidogrel can reduce diabetes-induced renal fibrosis in a streptozotocin-induced type 1 diabetes murine model and fibronectin involvement in this protective response. Diabetic and age-matched controls were sacrificed three months after the onset of diabetes, and additional controls and diabetic animals were further treated with clopidogrel or vehicle for three months. Diabetes induced renal morphological changes and fibrosis after three months. Clopidogrel, administered during the last three months, significantly decreased blood glucose, collagen and fibronectin expression compared to vehicle-treated diabetic mice. Diabetes increased TGF-β expression, inducing fibrosis via Smad-independent pathways, MAP kinases, and Akt activation at three months but returned to baseline at six months, whereas the expression of fibronectin and collagen remained elevated. Our results suggest that activation of TGF-β, CTGF, and MAP kinases are early profibrotic signaling events, resulting in significant fibronectin accumulation at the early time point and returning to baseline at a later time point. Akt activation at the three-month time point may serve as an adaptive response in T1D. Mechanisms of clopidogrel therapeutic effect on the diabetic kidney remain to be investigated as this clinically approved compound could provide novel approaches to prevent diabetes-induced renal disease, therefore improving patients' survival.