Abstract TKI resistance of advanced ccRCC patients usually leads to poor prognosis. Interaction between tumor cells and tumor-associated macrophages (TAMs) has been reported to facilitate tumor progression. However, the underlying mechanism remains unclear. This study employed cell functional experiments, IHC, ELISA, and subcutaneous tumor formation models to explore the interaction between ccRCC and TAMs. We found that the expression of NOL3 was upregulated in ccRCC using the online database. The NOL3 over-expressing ccRCC cell lines ACHN and 786-O showed enhanced proliferation and anti-apoptosis ability. In addition, THP1-derived macrophages co-cultured with ccRCC cells exhibited an increased trend towards M2-like polarization. TAMs could stimulate ccRCC to secret more VEGF, which promotes TKI resistance. ccRCC patients from two independent cohorts were screened to investigate the prediction accuracy of NOL3 and the relationship between NOL3 expression and TAMs infiltration. IHC staining quantified by H-score revealed a negative correlation between NOL3 expression and disease progression and a positive correlation with TAMs infiltration. Moreover, NOL3, CD163, and TNM Stage were also found to be the independent risk factors for predicting the outcome of ccRCC patients. Integrating NOL3, TAMs and TNM Stage could predict the prognosis of ccRCC with better accuracy. Overexpressing NOL3 enhanced the infiltration of TAMs and VEGF secretion in mouse tumors, while depletion of macrophages enhanced TKI efficacy. In summary, a positive feedback loop between ccRCC cells and TAMs induced by NOL3 promotes TKI resistance, and targeting NOL3/TAMs might be a potential strategy to alleviate TKI resistance.

Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC). Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments. It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines. Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.

Abstract TKI resistance of advanced ccRCC patients usually leads to poor prognosis. Interaction between tumor cells and tumor-associated macrophages (TAMs) has been reported to facilitate tumor progression. However, the underlying mechanism remains unclear. This study employed cell functional experiments, IHC, ELISA, and subcutaneous tumor formation models to explore the interaction between ccRCC and TAMs. We found that the expression of NOL3 was upregulated in ccRCC using the online database. The NOL3 over-expressing ccRCC cell lines ACHN and 786-O showed enhanced proliferation and anti-apoptosis ability. In addition, THP1-derived macrophages co-cultured with ccRCC cells exhibited an increased trend towards M2-like polarization. TAMs could stimulate ccRCC to secret more VEGF, which promotes TKI resistance. ccRCC patients from two independent cohorts were screened to investigate the prediction accuracy of NOL3 and the relationship between NOL3 expression and TAMs infiltration. IHC staining quantified by H-score revealed a negative correlation between NOL3 expression and disease progression and a positive correlation with TAMs infiltration. Moreover, NOL3, CD163, and TNM Stage were also found to be the independent risk factors for predicting the outcome of ccRCC patients. Integrating NOL3, TAMs and TNM Stage could predict the prognosis of ccRCC with better accuracy. Overexpressing NOL3 enhanced the infiltration of TAMs and VEGF secretion in mouse tumors, while depletion of macrophages enhanced TKI efficacy. In summary, a positive feedback loop between ccRCC cells and TAMs induced by NOL3 promotes TKI resistance, and targeting NOL3/TAMs might be a potential strategy to alleviate TKI resistance.

BACKGROUND:Laparoscopic partial nephrectomy has been widely used in renal cell carcinoma treatment. The efficacy of GreenLight laser on Laparoscopic partial nephrectomy is still unknown.AIM:To present the first series of laparoscopic partial nephrectomy (LPN) by GreenLight laser enucleation without renal artery clamping. Due to the excellent coagulation and hemostatic properties of the laser, laser-assisted LPN (LLPN) makes it possible to perform a "zero ischemia" resection.METHODS:Fifteen patients with T1a exogenous renal tumors who received high-power GreenLight laser non-ischemic LPN in our hospital were retrospectively analyzed. All clinical information, surgical and post-operative data, complications, pathological and functional outcomes were analyzed.RESULTS:Surgery was successfully completed in all patients, and no open or radical nephrectomy was performed. The renal artery was not clamped, leading to no ischemic time. No blood transfusions were required, the average hemoglobin level ranged from 96.0 to 132.0 g/L and no postoperative complications occurred. The mean operation time was 104.3 ± 8.2 min. The postoperative removal of negative pressure drainage time ranged from 5.0 to 7.0 d, and the mean postoperative hospital stay was 6.5 ± 0.7 d. No serious complications occurred. Postoperative pathological results showed clear cell carcinoma in 12 patients, papillary renal cell carcinoma in 2 patients, and hamartoma in 1 patient. The mean creatinine level was 75.0 ± 0.8 μmol/L (range 61.0-90.4 μmol/L) at 1 mo after surgery, and there were no statistically significant differences compared with pre-operation (P > 0.05). The glomerular filtration rate ranged from 45.1 to 60.8 mL/min, with an average of 54.0 ± 5.0 mL/min, and these levels were not significantly different from those before surgery (P > 0.05).CONCLUSION:GreenLight laser has extraordinary cutting and sealing advantages when used for small renal tumors (exogenous tumors of stage T1a) during LPN. However, use of this technique can lead to the generation of excessive smoke.

目的 探讨智能互动定性定量分析(IQQA)技术应用于中度复杂性肾肿瘤腹腔镜肾部分切除术的可行性、安全性和有效性.方法 选择2018年1月—2019年6月收治的16例中度复杂性肾肿瘤(R.E.N.A.L评分＞6?9分)患者,男10例、女6例,年龄为(55.8±8.3)岁,肾肿瘤R.E.N.A.L评分为(7.6±0.7)分.所有患者均于IQQA技术支持下行腹腔镜肾部分切除术.获取肾脏CTA检查的原始影像学数据,利用IQQA平台进行三维重建,通过操作平台多角度旋转、多层面系统化分析肾肿瘤与血管、集合系统的毗邻关系,进行手术规划和模拟,制订出个性化、精准的腹腔镜下肾部分切除术的方案.记录患者的手术时间、肾动脉阻断时间、术中出血量、术后引流管留置时间、术后并发症发生情况、术后住院天数,以及手术前和术后3个月血清肌酐水平、患肾肾小球滤过率(GFR).术后3个月随访时复查胸部CT、肾脏CT,观察肿瘤有无复发和转移.结果 16例患者均顺利完成手术,无1例患者中转开放性手术或改行根治性肾切除术.手术时间为(74.7±12.7)min,肾动脉阻断时间为(21.8±4.4)min,术中出血量为(63.8±38.9)mL;术后引流管留置时间为(6.3±1.6)d,术后住院时间为(6.9±1.7)d.术后患者均无出血、漏尿、感染、切口裂开、肺部感染等并发症发生.术后3个月血清肌酐水平为(80.6±11.4)μmol/L,与术前的(82.8±9.5)μmol/L的差异无统计学意义(P＞0.05).术后3个月患肾GFR为(49.6±7.9)mL/min,显著低于术前的(56.0±6.9)mL/min(P＜0.05).术后3个月患者胸部CT、肾脏CT检查均未见肿瘤复发和转移.结论 在IQQA技术辅助下对中度复杂性肾肿瘤行腹腔镜肾部分切除术更加精准,有利于提高中度复杂性肾肿瘤行腹腔镜肾部分切除术的成功率,患者肾功能得以较好的保护,该方法在技术上安全、可行.

目的:探讨腹腔镜保留肾单位手术中应用"2+1"缝合技术联合早期序贯开放血流法治疗T1b期单发肾肿瘤的安全性及疗效.方法:回顾分析2017年1月至2018年7月为22例T1b期单发肾肿瘤患者采用"2+1"缝合技术联合早期序贯开放血流法行腹腔镜保留肾单位手术的临床资料,肿瘤直径平均(5.4±0.8)cm,R.E.N.A.L评分平均(7.5±0.8)分.结果:患者均顺利完成手术,无一例中转开放手术.手术时间平均(136.5±31.2)min,术中出血量平均(135.0±40.6)mL,热缺血时间平均(15.0±2.3)min,术中、术后无一例输血,切缘均为阴性,术后均无漏尿、切口感染、患侧肾脏萎缩等并发症发生.结论:腹腔镜保留肾单位手术中应用"2+1"缝合技术联合早期序贯开放血流法治疗T1b期单发肾肿瘤,术中出血可控,热缺血时间可得到较好控制,手术安全、可靠.

Objective:To explore the safety and efficacy of laparoscopic non-blocking partial nephrectomy assisted by high power lateral green laser in the treatment of T 1a renal tumor. Methods:The clinical data of 10 patients with T1a stage renal tumor from February 2021 to April 2021 in department of urology, Gongli hospital affiliated to Naval Military Medical University were retrospectively analyzed. There were 7 males and 3 females, aged 47.0-74.0 years, with average of(58.8±9.7)years old. The diameter of the tumor ranged from 2.0 cm to 3.8 cm, with an average of (3.1±0.6)cm. There were 6 cases on the left side and 4 cases on the right side, locate on lumbar side in 9 cases and ventral sied in 1 case. The R. E.N.A.L score was 4.0-6.0, with an average of (5.0±0.8). The preoperative creatinine was 66.9-90.1μmol/L, with an average of (75.1±9.0)μmol/L, preoperative GFR of 44. 6- 67. 3 ml /min, with an average of(56.7±7.7)ml/min, preoperative hemoglobin level of 119.0-156.0g/L, with an average of (135.8±11.4)g/L. All patients underwent laparoscopic non-blocking partial nephrectomy assisted by 180w lateral green laser, free the surrounding area of the tumor fully and completely expose the renal tumor. The laser fiber was placed through the green laser hand piece, and the fiber was connected with normal saline to wash the strip. The initial green laser vaporization power was set at 80W, and the hemostasis power at 35W.About 3mm away from the edge of the tumor, and one optical fiber away from the renal parenchyma, the renal parenchyma was cut with 80W power. In order to reduce the interference by smoke, high-pressure flushing was used through the optical fiber while vaporizing, and an attractor was used to push and peel the tumor. In case of bleeding during operation, hemostatic power can be used to close the bleeding point and gradually advance until the tumor was completely removed. The wounds of renal inner medulla and renal outer cortex were continuously sutured in 1-3 layers with barbed suture. It involved 9 cases via retroperitoneal approach and 1 case via abdominal approach. The operation time, postoperative hemoglobin decrease, extraction time of negative pressure drainage, postoperative hospital stay, postoperative pathology and postoperative complications were recorded, and the serum creatinine level and GFR level of the affected side were followed up 1 month after operation.Results:All the operations were successfully completed, and there was no conversion to open surgery or radical nephrectomy. One case changed to scissors fast resection and sutured hemostasis due to severe intraoperative bleeding. The operation time was 90.0-120.0 min, with the average of (104.5±9.0)min. The postoperative hemoglobin level was 96.0-132.0g/L, with an average of (115.2±11.8)g/L, and the difference was statistically significant ( P<0.05). The postoperative hemoglobin decreased from 12.0g/L to 25.0g/L, with an average of (20.6±4.6)g/L. The time of vacuum drainage was 5.0-7.0 days, with an average of (5.7±0.7)d. Postoperative hospital stay was 6.0-8.0 days, with an average of (6.7±0.7)d. No bleeding, urinary leakage and other complications occurred in all patients. There were 7 cases of clear cell carcinoma, 2 cases of papillary renal cell carcinoma and 1 case of angiomyolipoma. All margins were negative. One month after operation, creatinine ranged from 66.0 to 90.4μmol/L, with an average of (76.8±8.3)μmol/L, which was not significantly different compared with that before operation ( P>0.05). One month after operation, GFR was 45.1-60.8 ml/min, and with an average of (55.5±4.7)ml/min, and there was no significant difference compared with preoperative data( P>0.05). Conclusions:For T 1aN 0M 0 stage and exophytic renal tumors, laparoscopic non-blocking partial nephrectomy assisted by lateral green laser is safe and effective.

Objective:To investigate the feasibility, safety and effectiveness of laparoscopic partial nephrectomy for cystic tumor of the renal hilus.Methods:The data of 6 patients with cystic tumor of renal hilus treated by laparoscopic partial nephrectomy in the three centers from January 2017 to December 2019 were analyzed retrospectively. There were 5 males and 1 females, with a median age of 45(10) years and body mass index of 23.3(1.5) kg/m2, maximum tumor diameter 3.7(0.4) cm, the R.E.N.A.L score 8.5(1.0), the tumor stage was T1. The preoperative creatinine level was 68(12) μmol/L. The glomerular filtration rate (GFR) was 47.3(5.5) ml/min. The hemoglobin level was 138(17) g/L. The success rate, opening rate, operation time, artery blocking time, intraoperative bleeding volume, postoperative drainage tube retention days, postoperative complications, postoperative hospital stay days, renal function and tumor prognosis indexes of 6 patients were collected for statistical analysis.Results:Laparoscopic partial nephrectomy was successfully completed in all patients, and there was no conversion to open surgery or radical nephrectomy. The median operation time was 112(20) min, the renal artery occlusion time was 34(7) min, the intraoperative hemorrhage was 33(22) ml, and the postoperative hospital stay was 6.5(1.0) d. There were no postoperative complications such as bleeding and urinary leakage. Postoperative pathology showed 5 cases of renal malignant tumor and 1 case of renal cyst. The surgical margin was negative. The median creatinine was 81(12) μmol/L in 3 months after operation, which had no significant difference compared with that before operation (P>0.05). The GFR of kidney in 3 months after operation was 37.0(4.4) ml/min, which had significant difference compared with that before operation (P<0.05). The hemoglobin level was 127(15) g/L after operation, and the difference was statistically significant compared with that before operation. After 3 months follow-up, no tumor recurrence or metastasis was found in CT.Conclusion:Laparoscopic partial nephrectomy is a feasible method for the patients with cystic renal carcinoma in the hilum of kidney, which is beneficial for the better protection of renal function and the exact perioperative effect.

目的:探讨肾肿瘤悬吊法在“零缺血”腹腔镜下肾部分切除术中的应用价值.方法:回顾性分析2017年1月～2018年1月海军军医大学附属公利医院和海军军医大学附属东方肝胆外科医院12例患者应用肾肿瘤悬吊法在完全无肾动脉阻断的“零缺血”条件下开展腹腔镜下肾部分切除术,收集患者的一般临床基线资料,在后腹腔镜下采用肾肿瘤悬吊法行“零缺血”肾部分切除术:游离肾周脂肪暴露肾肿瘤,但保留肾肿瘤上方的脂肪.取肿瘤上方的脂肪向上提拉,用Hem-o-lock将肿瘤上方脂肪悬吊到上方筋膜、腹膜反折等组织(具体可根据术中情况评估选择)上,使肿瘤与肾脏之间保持一定的张力.使用腹腔镜剪刀在肿瘤周围0.5 cm左右处分离肿瘤,另外一个操作孔置入腹腔镜下吸引器,将肾脏创面的出血充分吸走,保持视野清晰并帮助调整瘤体方向,保证完整切除肿瘤,对肾脏创面进行连续缝合.收集12例患者的手术时间、肿瘤切除并缝合时间、术中出血量、术后引流管留置天数、术后并发症、术后住院天数等指标,记录术后6个月患肾肾小球滤过率(GFR)、血红蛋白及肌酐等相关实验室指标以及肿瘤学预后指标,进行统计分析.结果:12例患者均成功实施肾肿瘤悬吊法腹腔镜下“零缺血”肾部分切除术,无改行肾动脉阻断或者中转开放手术病例,手术成功率达100％,中位手术时间为105(70～135) min,中位肿瘤切除并缝合时间为17(14～25) min,中位术中出血量185(70～350) mL,中位术后引流管留置时间为5(4～6)d,中位术后住院天数为6(5～7)d,术后无出血、尿漏、感染、切口裂开等相关并发症.12例患者术后6个月复查肾脏CT、胸部CT等未见肿瘤复发、转移,术前以及术后6个月血红蛋白指标、肌酐水平、患肾GFR差异无统计学意义.结论:完全无阻断的“零缺血”腹腔镜下肾部分切除术术中应用肿瘤悬吊法能够保证手术的安全性和可行性,最大程度地保护肾功能,使患者在肾部分切除术中能够得到最大程度的获益.

目的:探讨肾周脂肪平均密度对腹腔镜肾部分切除术的影响.方法:回顾性分析2014年4月～2018年4月上海长征医院泌尿外科135例腹腔镜肾部分切除术患者.通过CT影像学资料对肾周脂肪平均密度进行计算,并将患者分为高密度组和低密度组,比较两组患者手术时间、BMI、术中出血、R.E.N.A.L、PAUDA评分及肾周脂肪平均密度等指标.结果:高密度组与低密度组手术时间比较差异有统计学意义(P＜0.05),两组患者在BMI、术中出血量、肾周脂肪厚度(PD)等方面比较差异无统计学意义.结论:本研究发现MAP肾周脂肪评分无法准确地评估肾周脂肪含量,而肾周脂肪平均密度可作为肾周脂肪的评估指标.

目的:探讨分析高血压不良反应与舒尼替尼治疗晚期转移性肾癌疗效的相关性.方法:回顾性收集我院2009年1月～2016年6月65例舒尼替尼治疗的晚期转移性肾癌患者的临床资料,男42例,女23例;年龄44～75岁,平均63岁;84.6％的患者接受手术治疗(肾癌根治性切除或保留肾单位切除),肿瘤病理均为肾透明细胞癌,最常见的转移部位为肺(73.8％).所有患者均采用舒尼替尼标准治疗方案:50 mg/d,服用4周,停用2周.每2个周期通过CT检查评价药物疗效,每个疗程的第1天和第28天检测血压.比较有无舒尼替尼诱导的高血压不良反应[收缩压≥140 mmHg(1 mmHg=0.133 kPa)或者舒张压≥90 mmHg]对肿瘤疗效的影响.结果:服用靶向药物期间,根据是否出现高血压不良反应进行分组,分为高血压组(30例)和血压正常组(35例),两组基线特征比较差异均无统计学意义.高血压不良反应在舒尼替尼治疗的第1疗程或者第2疗程出现,出现收缩期的高血压(中位时间:第1疗程,1～9疗程)比舒张期的高血压(中位时间:第2疗程,1～11疗程)更为早期.在12个月的随访中,高血压组客观有效率(ORR)显著高于血压正常组(56.7％ vs.28.6％,P=0.016).同时亚组分析收缩期高血压组或舒张期高血压组与收缩压正常组或舒张压正常组比较差异均有统计学意义(P=0.039、P=0.038).长期随访过程中,高血压组平均无进展生存期(PFS)较血压正常组显著延长(13.4个月vs.8.7个月,P=0.002).结论:在舒尼替尼治疗过程中,晚期转移性肾癌患者出现高血压不良反应可获得更好的肿瘤控制,更长的PFS,适合作为预测靶向药物疗效的有效指标.

目的:目的:探讨个性化"缩短热缺血时间"技术辅助腹腔镜肾部分切除术治疗T1期肾肿瘤的安全性及有效性.方法:回顾分析2014年1月至2018年1月接受腹腔镜下肾部分切除术的189例T1期肾肿瘤患者的临床资料.其中男112例,女77例,平均(56.51±14.31)岁,肿瘤直径平均(3.80±1.68)cm,内生型78例,外生型111例,平均R.E.N.A.L评分(7.45±1.78)分.个性化"缩短热缺血时间"技术组分为:标准无阻断技术、预留缝线无阻断技术、术前DSA超选栓塞无阻断技术、早期序贯开放血流法、肾动脉全阻断(2+1缝合法).结果:189例患者均顺利完成腹腔镜下肾部分切除术.97例个性化选择的患者中83例(85.6％)完成个性化手术方式,入选个性化组;92例肾癌患者入选传统组(全阻断).两组患者术前临床资料差异无统计学意义.个性化组手术时间、术中出血量多于传统组(P<0.001),两组术后血红蛋白改变、术后住院时间等差异无统计学意义.术后第6个月、第12个月,个性化组肾功能恢复情况占优势,差异有统计学意义.结论:个性化"缩短热缺血时间"技术利用肿瘤的特性选择合理的术式,尽可能保护患者术后肾功能,安全可行.

Objective To explore the efficacy and tolerance of adverse reactions of gene detection technique in guiding individualized targeted therapy for advanced metastatic renal cell carcinoma.Methods Retrospective analysis was performed on the clinical data of 62 patients with advanced metastatic renal cell carcinoma before and after receiving targeted drug treatment in our department from October 2015 to October 2017.Among the 62 patients,there were 36 males and 26 females,with an average age of (54 ± 13) years old.16 patients were treated with sunitinib,20 patients were treated with sorafenib and 26 patients were treated with pazopanib.A total of 28 patients (individualized group) were selected to receive targeted drug according to the results of gene detection,and 34 patients were treated with targeted drug empirically (empirical group).In individualized group,there were 17 males and 11 females with the average age of (51.3 ± 15.6) years old.20 patients accepted the operation.The distant metastasis included bone metastasis in 21 cases,lung metastasis in 7 cases,liver metastasis in 16 cases,epidermal metastasis in 4 cases and lymphatic metastasis in 14 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 15,7,6,respectively.7 patients were treated with sunitinib,8 patients were treated with sorafenib and 13 patients were treated with pazopanib.In empirical group,there were 19 males and 15 females with the average age of (56.3 ± 10.1) years old.22 patients accepted the operation.The distant metastasis included bone metastasis in 20 cases,lung metastasis in 5 cases,liver metastasis in 13 cases,epidermal metastasis in 3 cases and lymphatic metastasis in 15 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 20,g,6,respectively.9 patients were treated with sunitinib,12 patients were treated with sorafenib and 13 patients were treated with pazopanib.The baseline characteristics of the two groups of patients,including gender,age,whether operation was performed,site of metastasis,and risk of MSKCC,didn't show significant difference.Patients in both groups received the standard treatment regimen and the follow-up duration was 4-26 months to observe the efficacy,progression-free survival and tolerance to adverse reactions of the targeted therapy.Results After 12 months of treatment,15 patients in the individualized group was recorded objective remission.7 patients in the empirical group was recorded objective remission,as well.The tumor control efficacy of the individualized group was significantly better than that of the empirical group (46.4％ vs.20.6％,P =0.03).Meanwhile,the median progression-free survival time (15.2 months,3.7-24.2 months) in the individualized group was significantly longer than that in the empirical group (12.1 months,2.8-22.1 months) (P =0.009).Compared with the empirical group,the higher incidence of targeted treatment-related adverse reactions occurred in the individualized group,including thrombocytopenia (46.4％ vs.17.6％ P =0.014),leukopenia (46.4％ vs.17.6％ P =0.005),hypertension (71.4％ vs.44.1％,P =0.031) and hypothyroidism(60.7％ vs.29.4％,P=0.013).Conclusions Compared with the patients with empirical drugs,the application of gene detection technique to select individualized targeted drugs for the treatment of advanced metastatic renal cancer is obvious curatively effective,and to a certain extent extends the progression-free survival time of patients.

Advanced-stage prostate cancer (PCa) is often diagnosed with bone metastasis, for which there are limited therapies. Transforming growth factor β (TGF-β) is known to induce epithelial–mesenchymal transition (EMT), and abundance of TGF-β in the bone matrix is one of the important growth factors contributing to bone metastasis. TGF-β is reported as a key mediator of bone metastasis, but the underlying mechanism has not been elucidated. It was found in our study that Interferon-inducible Transmembrane Protein 3 (IFITM3) played a key role in the regulation of malignant tumor cell proliferation, invasion, and bone migration by binding to Smad4, thus activating the TGF-β-Smads Signaling Pathway. Lentivirus-mediated short hairpin RNA (shRNA) knockdown of IFITM3 inhibited cell proliferation and colony formation, induced apoptosis and inhibited migration by reversing EMT and downregulating the expression of metastasis-related molecules including FGFs and PTHrP. Microarray analysis showed that IFITM3 knockdown could alter the MAPK pathway associated with TGF-β-Smads signaling. By knocking down and overexpressing IFITM3, we demonstrated that IFITM3 expression level had an effect on MAPK pathway activation, and this change was more pronounced upon exogenous TGF-β stimulation. These results suggest that IFITM3 played an oncogenic role in PCa progression and bone metastasis via a novel TGF-β-Smads-MAPK pathway.

目的:探讨分析培唑帕尼新辅助治疗在减瘤性肾切除术治疗转移性肾癌患者中的安全性和有效性.方法:回顾性分析2017年9月～2018年4月接受培唑帕尼新辅助治疗的5例晚期转移性肾癌患者的临床资料,男3例,女2例,平均年龄60(48～69)岁,4例患者存在肺部转移,2例患者存在骨转移(分别为腰椎和肋骨).培唑帕尼新辅助治疗方案:800 mg口服1次/d,连续性服用12～14周,每4周通过CT检查评价药物疗效,明确临床疗效后接受减瘤性肾切除术治疗.主要观察指标包括靶向药物不良反应、疗效、围手术期患者一般情况等.结果:培唑帕尼靶向治疗12～14周后,2例患者原发肾肿瘤病灶缩瘤(缩瘤率分别26.9％和12.4％),处于部分缓解(PR)状态;1例患者原发肾肿瘤病灶处于稳定(SD)状态;1例患者原发肾肿瘤出现疾病进展(PD),终止了培唑帕尼新辅助治疗;1例患者新辅助服药期间出现严重的腹泻不良反应,患者放弃培唑帕尼新辅助治疗计划.靶向获益的3例患者接受了减瘤性患肾切除术治疗,2例肿瘤病理为肾透明细胞癌,1例为成人肾母细胞瘤.术后恢复良好,无出血、伤口愈合延迟、血肌酐升高等常见并发症.术后2～3周继续服用培唑帕尼.术后随访,远处转移灶(肺、骨)控制良好,尚未见PD.结论:培唑帕尼新辅助治疗可以安全、有效地应用于晚期转移性肾癌患者的减瘤性患肾切除术,但仍需要前瞻性随机对照研究进行验证.

目的:探讨分析早期开放血流法在肾肿瘤腹腔镜肾部分切除术中的安全性及有效性.方法:回顾性分析2016年1月～2017年6月在我院行腹腔镜下肾部分切除术的60例肾肿瘤患者的临床资料.其中男35例,女25例,平均年龄(59.57±11.18)岁;平均肿瘤直径(4.40±0.93) cm;背侧40例,腹侧20例.肾动脉早期开放血流法简要手术过程:①肾动脉阻断下,切除肾肿瘤,缝合肾创面血管及集合系统;②肾动脉解除阻断(开放血流)下,缝合关闭肾外层创缘.结果:60例肾肿瘤患者均顺利完成腹腔镜下肾部分切除术,其中28例患者采用肾动脉早期开放血流(早期开放血流组),32例患者采用传统肾动脉全阻断(传统全阻断组).两组肾肿瘤患者基线特征相关指标(年龄、性别、肿瘤大小、肿瘤位置、R.E.N.A.L.评分)差异无统计学意义.早期开放血流组和传统全阻断组术中平均手术时间[(103.93±29.86) min vs.(105.00±26.27)min]和术后住院天数[(6.35±1.14)dvs.(6.49±1.02) d]比较差异均无统计学意义.早期开放血流组平均出血量多于传统全阻断组[(107.14±28.53) ml vs.(83.44±31.38) ml,P＜0.01],但两组患者均无输血事件发生.早期开放血流组热缺血时间显著低于传统全阻断组[(14.89±4.21)min vs.(21.84±4.30) min,P＜0.01].术后传统全阻断组出现1例出血并发症,两组均无切缘阳性并发症发生.术后1年随访中,两组肾功能恢复比较差异无统计学意义,未见肿瘤复发转移.结论:肾动脉早期开放血流法,显著缩短肾部分切除术的热缺血时间,是一种安全可行的手术方式,值得临床应用推广.

Objective To explore the application of three-dimensional intelligent qualitative and quantitative analysis system (IQQA) in the planning,simulation and implementation of precise surgery for bilateral renal tumors.Methods A retrospective analysis a total of 7 patients with bilateral kidney tumors in our center from June 2017 to August 2018 was performed.There were 5 males and 2 females,with an average age of (54.6 ± 6.0) years,ranging 47.0-63.0 years.The average BMI index was (23.4 ± 2.4) kg/m2,ranging 21.2-28.0 kg/m2.The average diameter of 14 renal tumors in 7 patients was (3.8 ± 1.1) cm,ranging 1.9-5.3 cm.The average R.E.N.A.L score was 6.6 ± 1.2,ranging 5.0-9.0.The tumor stage was T1N0M0.The mean preoperative hemoglobin,albumin,creatinine and GFR were (138.6 ± 17.0)g/L and (47.3 ± 2.5 g/L),(51.6 ± 19.1) μmol/Land (56.9 ± 6.7) ml/min,respectively.Before operation,the original data of CT were input into IQQA system.Then we reconstructed kidney,blood vessel,collecting system and tumors using system.And the structure of kidney,tumors and vessels was visualized directly.The systematic analysis of the operation is carried out at terminals vary from various angles,and the surgical resection simulation.The position,angle and curvature of the cut surface are adjusted according to the effect.The plan of partial nephrectomy is designed.The resection area,remaining area of kidney is calculated.In this way,we can construct individualized and accurate laparoscopic partial nephrectomy planning before operation.Last,we carried out the operation according to the designed plan.The laparoscopic standard partial nephrectomy was performed in 11 cases.The laparoscopic selective partial nephrectomy was performed in 2 cases.One underwent laparoscopic partial nephrectomy without obstruction.We achieved precise resection of tumors and rapid suture of wounds according to the preoperative planning of excision and suture.We collected of the surgical success rate,conversion to opening rate,operation time,warm ischemia time,intraoperative bleeding volume,complications and hospitalization after operation.The related laboratory indicators such as eGFR and creatinine were followed up for 3 months,and the prognostic indicators such as renal CT and pulmonary CT for 6 months after operation were evaluated and analyzed.Result 14 renal tumors were successfully reconstructed by IQQA in 7 patients.The operations were completed successfully without conversion to open surgery or radical nephrectomy.The average operative duration was (68.9 ± 9.2) minutes,ranging 50.0-80.0 minutes.The average renal artery occlusion duration was (20.7 ± 4.1) minutes,ranging 15.0-29.0 minutes.The average intraoperative bleeding volume was (70.7 ± 29.7) ml,ranging 30.0-120.0 ml.The average indwelling time of drainage tube was (5.5 s0.7) days,ranging 5.0-7.0 days.The average hospitalization time was (6.3 ± 0.5) days,ranging 6.0-7.0 days.There were no perioperative complications such as bleeding,urinary leakage,infection,incision dehiscence and pulmonary infection.Postoperative pathology revealed 13 clear cell renal carcinoma and 1 renal angiomyoma.No recurrence or metastasis was found in chest CT and lung CT after 6 months follow-up.The creatinine and GFR in 3 months after operation were (52.0 ± 15.2) μmol/L(36.0-72.0 μmol/L) and (56.7 ± 5.3) ml/min(46.7-66.3 ml/min).There was no significant difference of creatinine and GFR with the preoperative (P ＞ 0.05).The mean Hb and albumin levels in 3 months after operation were (120.9 ± 17.0) g/L(90.0-147.0 g/L) and (41.4 ± 2.6) g/L (38.0-46.0 g/L),which were significantly lower than those before operation (P ＜ 0.05).Conclusions The three-dimensional intelligent qualitative and quantitative analysis system (IQQA) can visualize the kidney,tumor and the vasculature of bilateral kidney tumors by preoperative three-dimensional reconstruction.The optimal surgical plan of partial nephrectomy can be designed by preoperative operation planning and computer terminal in order to enhance the safety of partial nephrectomy for bilateral kidney tumors and preserve the possibility of kidney,and protect the renal function to the greatest extent.To accurately predict the retention of renal function after operation,so that patients with bilateral renal tumors can get the greatest benefit in partial nephrectomy.

Background: Prostate cancer (PCa) is one of the most common malignancies and a major Fading cause of cancer-related deaths in males. And it is necessary to explore new molecular targets to enhance diagnosis and treatment level of the PCa. Serine/threonine protein phosphatase 5 (PPP5C) is a vital molecule that Involve in complex cell physiological activity. Purpose: The objective of this study was to detecte the expression level of PPP5C in the tissue of prostate cancer patients and further discussed the PPP5C biological function and mechanisms on the PCa. Methods: The expression level of PPP5C was analyzed by immunohistochemistry and ONCOMINE datasets. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of PPP5C in prostate cancer cell. Cell viability and proliferation were measured using MTT and colony formation, and the cell cycle and apoptosis was analyszed by flow cytometry. The changes of downstream protein level and protein phosphorylation level were detected by western blot. Results: PPP5C was highly expressed in PCa tissue as analyzed by immunohistochemistry and ONCOMINE datasets. PPP5C Knockdown inhibited cell proliferation and colony formation in PCa cells. Flow cytometry analysis showed that DU145, PC3 and 22RV1 PCa cells deprived of PPP5C were arrested in GO/G1 phase and became apoptotic. Western blot analysis indicated that PPP5C knockdown could promote JNK and ERK phosphorylation. Conclusion: Our study indicated that the PPP5C may become a new potential diagnostic biomarker and therapeutic target for the PCa.

Prostate cancer (PCa) is one of the most commonly diagnosed urological malignancies. However, there are limited therapies for PCa patients who develop biochemical recurrence after androgen deprivation therapy (ADT). In the present study, we investigated the therapeutic efficacy and mechanism of α-Viniferin (KCV), an oligostilbene of trimeric resveratrol, against human PCa cells and found that it markedly inhibited the proliferation of LNCaP, DU145, and PC-3 cancer cells in a time- and dose-dependent manner, and had a strong cytotoxicity in non-androgen-dependent PCa cells. In addition, KCV inhibited AR downstream expression in LNCaP cells, and inhibited activation of GR signaling pathway in DU145 and PC-3. Further investigation indicated that KCV could induce cancer cell apoptosis through AMPK-mediated activation of autophagy, and inhibited GR expression in castration-resistant prostate cancer(CRPC). These findings suggest that KCV may prove to be a novel and effective therapeutic agent for the treatment of CRPC.

Aim: There is little knowledge about the expression profile and function of circular RNAs (circRNAs) in prostate cancer (PCa). Methods: The expression profiles of circRNAs in RWPE-1, 22RV1 and PC3 cells were explored via high-throughput circRNAs sequencing and validated by real-time qPCR. The roles of differentially expressed circRNAs were evaluated by bioinformatics analyses. Results: Altogether 9545 circRNAs were identified and hundreds of differentially expressed circRNAs were recognized. CircRNA–miRNA networks analysis showed that many circRNAs, including circSLC7A6, circGUCY1A2 and circZFP57 could cross-talk with tumor-related miRNAs such as miR-21, miR-143 and miR-200 family. Conclusion: The results of our bioinformatics analyses suggested that circRNAs should play critical roles in the development and progression of PCa.