[Correlation between adipokine and clinicopathological features and prognosis in upper tract urothelial carcinoma].

OBJECTIVE: To investigate the correlation between expression levels of adipokine and clinicopathological features and prognosis of patients with upper tract urothelial carcinoma (UTUC) based on immunohistochemical staining and bioinformatics analysis. METHODS: The 8 adipokines in this study included adiponectin (AdipoQ), leptin (LEP), interleukin (IL)-6, IL-10 and their receptors (AdipoR1, AdipoR2, LEPR, IL-6R, IL-10RA, IL-10RB). Tissue samples of patients with UTUC who underwent surgical treatment in Peking University People's Hospital from January 2014 to April 2021 were selected for immunohistochemical staining. Their quantitative gene expression data were calculated by H-Score, and relevant clinical and follow-up data were collected retrospectively. Transcription group sequencing data of UTUC patients in Gene Expression Omnibus database (GSE134292 dataset) were downloaded for comparison. Chi-square test or t-test was used to compare the expression level of adipokine between non-muscle invasive group and muscle invasive group. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were utilized to analyze independent predictors of overall survival (OS), disease-free survival (DFS), intravesical recurrence-free survival (IVRFS) in the both cohorts. The P < 0.05 was considered statistically significant. RESULTS: In the study, 63 tissue samples of the patients with UTUC who underwent surgical treatment in Peking University People's Hospital and 57 UTUC patients in GSE134292 dataset were selected. In immunohistochemical cohort, the expressions of AdipoQ (P=0.003 6), AdipoR1 (P=0.006 5), LEP (P=0.007 7), IL-10 (P=0.006 9), and IL-10RA (P=0.008 9) were statistically higher in muscle invasive group. In GSE134292 cohort, the expressions of AdipoR1 (P=0.000 4), AdipoR2 (P=0.000 4), IL-6 (P=0.005 0), IL-10 (P=0.001 7), and IL-10RA (P=0.008 1) were statistically higher in muscle invasive group. Kaplan-Meier survival curve and multivariate Cox regression analysis showed that high IL-10RA expression was an independent predictive factor of IVRFS (P=0.044, HR=0.996, 95%CI: 0.992-0.998) in immunohistochemical cohort, which was confirmed in GSE134292 cohort (P=0.014, HR=0.515, 95%CI: 0.304-0.873). CONCLUSION: The expression levels of AdipoQ, AdipoR1, IL-10, and IL-10RA were correlated with tumor stage, suggesting that these adipokines played important roles in tumor progression. IL-10RA was an independent predictor of IVRFS, suggesting that IL-10 and its receptor played a critical role in tumor recurrence.

[Correlation between metabolic syndrome and prognosis of patients with clear cell renal cell carcinoma].

OBJECTIVE: To investigate the effects of MetS on the prognosis of patients with clear cell renal cell carcinoma (ccRCC). METHODS: Clinical and pathological data and the laboratory test of ccRCC 342 patients with diverticular stones who underwent ccRCC who underwent radical or partial nephrectomy were retrospectively collected and analyzed.The patients were divided into MetS group and non-MetS group, and the subgroups were defined according to the tumor size. The overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) of the two groups were analyzed by univariate Cox analysis, and the subgroup analyses were also performed. Kaplan-Meier survival curve and survival analysis for OS, CSS, and PFS of the two groups and the subgroups were conducted. RESULTS: Univariate Cox analysis showed that MetS was a protective factor of postoperative OS [hazard ratio (HR)=0.551, 95%CI: 0.321-0.949, P=0.031], CSS (HR=0.460, 95%CI: 0.234-0.905, P=0.025), and PFS (HR 0.585, 95%CI: 0.343-0.998, P=0.049) in the patients with ccRCC. In the subgroup with tumor size≤4 cm, MetS was not associated with postoperative OS (HR=0.857, 95%CI: 0.389-1.890, P=0.702), CSS (HR=1.129, 95%CI: 0.364-3.502, P=0.833), and PFS (HR=1.554, 95%CI: 0.625-3.864, P=0.343). In the subgroup with tumor size>4 cm, Mets was a protective factor of postoperative OS (HR=0.377, 95%CI: 0.175-0.812, P=0.013), CSS (HR=0.280, 95%CI: 0.113-0.690, P=0.006), and PFS (HR=0.332, 95%CI: 0.157-0.659, P=0.002); Obesity was a protective factor of postoperative CSS (HR=0.464, 95%CI: 0.219-0.981, P=0.044), and PFS (HR=0.445, 95%CI: 0.238-0.833, P=0.011). Kaplan-Meier survival analysis showed that the long-term survival of patients with MetS was better than those without MetS in OS (P=0.029), CSS (P=0.021), and PFS (P=0.046); for the subgroup with tumor size≤4 cm, there was no significant difference in postoperative OS (P=0.702), CSS (P=0.833), and PFS (P=0.339) between patients with and without MetS; For the subgroup with tumor size>4 cm, the OS (P=0.010), CSS (P=0.003), and PFS (P=0.001) of patients with MetS were better than those without MetS. CONCLUSION: MetS was a protective factor of postoperative OS, CSS, and PFS in the patients with ccRCC, which was more obvious in subgroup with tumor size>4 cm. And obesity, the component of MetS, was correlated with postoperative OS and CSS.

[Risk factors of persistent hypertension in primary aldosteronism patients after surgery].

OBJECTIVE: To analyze the risk factors of persistent hypertension in patients who underwent adrenalectomy for primary aldosteronism and to evaluate the predictive value of the aldosteronoma resolution score (ARS) scoring system for surgical outcomes of adrenalectomy for primary aldosteronism. METHODS: We reviewed the clinical characteristics of patients who underwent adrenalectomy for primary aldosteronism from 2018 to 2021 at Peking University People' s Hospital to recognize risk factors of uncured hypertension after surgery. Based on the patient' s clinical outcomes, the patients were divided into complete success group and partial/absent success group. Risk factors for persistent hypertension were analyzed. The value of the ARS scoring system was assessed by the area under the curve (AUC). RESULTS: In this study, 112 patients were included. Most of the patients benefited from the surgery for 94.6% were a complete or partial clinical success after follow-up for at least 6 months. According to postoperative hypertension status, the patients were divided into complete success group (51 cases) and partial/absent success group (61 cases). There were statistical differences between the two groups in age, body mass index (BMI), waist circumference, duration of hypertension, number of preoperative antihypertension medications, preoperative systolic blood pressure, history of diabetes, history of cardiovascular and cerebrovascular diseases, serum creatinine, estimated glomerular filtration rate(eGFR), high-density lipoprotein cholesterol and triglyceride. Logistic regression analysis showed that age (OR=1.111, 95%CI: 1.029-1.199), waist circumference (OR=1.073, 95%CI: 1.013-1.137), pre-operative systolic blood pressure (OR=1.033, 95%CI: 1.008-1.060) and history of cardiovascular and cerebrovascular diseases (OR=16.061, 95%CI: 1.312-196.612) were the risk factors for uncured hypertension in primary aldosteronism patients after surgery, but female gender not. The median ARS in the complete success group was 4 and in the partial/absent success group, it was 2. Among the patients with ARS of 4-5, the cure rate of hypertension was 76.5%. The area under the curve of ARS was 0.743. CONCLUSION: The history of cardiovascular and cerebrovascular diseases is a significant risk factor for persistent hypertension after surgery in primary aldosteronism patients. ARS scoring system has a certain value in predicting the postoperative hypertension status of primary aldosteronism patients. However, further research is still needed on a prediction model for surgical outcomes of primary aldosteronism which is more suitable for the Chinese population is still needed.

[Optimal surveillance intensity of cystoscopy in intermediate-risk non-muscle invasive bladder cancer].

OBJECTIVE: To determine the optimal cystoscopic frequency for intermediate-risk non-muscle invasive bladder cancer. METHODS: Patients with intermediate-risk non-muscle invasive bladder cancer, who underwent transurethral resection of bladder tumor in Peking University People's Hospital from January 2001 to October 2019, were retrospectively analyzed. Their clinical, pathological and follow-up data were collected. In postoperative 2-year period, the patients were underwent cystoscopy every 3 to 6 months. Depending on recurrence and progression of the patients, we hypothesized three strategies of surveillance intensity in the first 2 years after surgery: model 1: 3-month intervals, model 2: 6-month intervals, and model 3: 12-month intervals. The differences in the numbers and time of delayed detection of recurrence and progression were compared among the three models. RESULTS: A total of 185 patients were enrolled, including 144 males (77.8%) and 41 females (22.2%). The median age was 68 (59-76) years. There were 118 cases (63.8%) with single tumor and 67 cases (36.2%) with multiple tumor. Of the patients 179 (96.8%) had stage Ta and 6 (3.2%) had stage T1. There were 108 cases (58.4%) with high-grade disease and 77 cases (41.6%) with low-grade disease. During the follow-up period of the first 2 years, 52 patients (28.1%) had recurrence, 133 cases (71.9%) had no recurrence, 11 cases (5.9%) had progression and 174 cases (94.1%) had no progression. Compared with model 1, 29 (55.8%) delayed detection of recurrence in model 2 vs. 41 (78.8%) delayed detection of recurrence in model 3, and the difference was statistically significant (P=0.012). The median delayed time of detecting recurrence was 1.00 months in model 1, 1.99 months in model 2 and 4.19 months in model 3, respectively. There were statistically significant differences between mode 1 and model 3 (P=0.001), and between model 2 and model 3 (P=0.013). Compared with model 1, 5 (45.4%) delayed detection of progression in model 2 vs. 8 (72.7%) delayed detection of progression in model 3, and the difference was not statistically significant. The median delayed time of detecting progression was 1.00 month in model 1, 2.00 months in model 2 and 3.00 months in model 3, respectively. There was no statistically significant difference among them. CONCLUSION: Although providing slightly slower detection of tumor recurrence and progression, compared with 3-month intervals of cystoscopy, 6-month intervals do not result in serious adverse outcomes and reduce cost and pain of the patients, which is feasible in intermediate-risk non-muscle invasive bladder cancer.

[Establishment of a mutation prediction model for evaluating the efficacy of immunotherapy in renal carcinoma].

OBJECTIVE: To establish a mutation prediction model for efficacy assessment, the genomic sequencing data of renal cancer patients from the MSKCC (Memorial Sloan Kettering Cancer Center) pan-cancer immunotherapy cohort was used. METHODS: The genomic sequencing data of 121 clear cell renal cell carcinoma patients treated with immune checkpoint inhibitors (ICI) in the MSKCC pan-cancer immunotherapy cohort were obtained from cBioPortal database (http://www.cbioportal.org/) and they were analyzed by univariate and multivariate Cox regression analysis to identify mutated genes associated with ICI treatment efficacy, and we constructed a comprehensive prediction model for drug efficacy of ICI based on mutated genes using nomogram. Survival analysis and time-dependent receiver operator characteristic curves were performed to assess the prognostic value of the model. Transcriptome and genomic sequencing data of 538 renal cell carcinoma patients were obtained from the TCGA database (https://portal.gdc.cancer.gov/). Gene set enrichment analysis was used to identify the potential functions of the mutated genes enrolled in the nomogram. RESULTS: We used multivariate Cox regression analysis and identified mutations in PBRM1 and ARID1A were associated with treatment outcomes in the patients with renal cancer in the MSKCC pan-cancer immunotherapy cohort. Based on this, we established an efficacy prediction model including age, gender, treatment type, tumor mutational burden (TMB), PBRM1 and ARID1A mutation status (HR=4.33, 95%CI: 1.42-13.23, P=0.01, 1-year survival AUC=0.700, 2-year survival AUC=0.825, 3-year survival AUC=0.776). The validation (HR=2.72, 95%CI: 1.12-6.64, P=0.027, 1-year survival AUC=0.694, 2-year survival AUC=0.709, 3-year survival AUC=0.609) and combination (HR=2.20, 95%CI: 1.14-4.26, P=0.019, 1-year survival AUC=0.613, 2-year survival AUC=0.687, 3-year survival AUC=0.526) sets confirmed these results. Gene set enrichment analysis indicated that PBRM1 was involved in positive regulation of epithelial cell differentiation, regulation of the T cell differentiation and regulation of humoral immune response. In addition, ARID1A was involved in regulation of the T cell activation, positive regulation of T cell mediated cyto-toxicity and positive regulation of immune effector process. CONCLUSION: PBRM1 and ARID1A mutations can be used as potential biomarkers for the evaluation of renal cancer immunotherapy efficacy. The efficacy prediction model established based on the mutation status of the above two genes can be used to screen renal cancer patients who are more suitable for ICI immunotherapy.

[The significance of preoperative evaluation for atlantoaxial reducibility should be reevaluated].

For treatment of atlantoaxial dislocation, the evaluation of reducibility used to be the main basis for its classification. In recent years, with the development of posterior reduction techniques, the treatment paradigm for atlantoaxial dislocation is gradually changing from a combined anterior and posterior approach to a direct posterior approach. Through posterior intra-articular release and distraction, part of atlantoaxial dislocation which is irreducible in traditional concept can become reducible. With the new proposed strategy based on posterior reduction techniques, the significance and necessity of preoperative evaluation for atlantoaxial reducibility should be reevaluated. Based on our clinical experience, we put forward our views on this hot topic for peer reference and criticism.

[Surgical treatment strategy for difficult-reducible atlantoaxial dislocation].

Objective: To discuss the surgical strategy for difficult-reducible atlantoaxial dislocation. Methods: Clinical data of 82 patients with difficult-reducible atlantoaxial dislocation underwent surgical treatment in the Department of Neurosurgery, Xuanwu Hospital from January 2018 to February 2019 were retrospectively reviewed. Total of 32 men and 50 women were included, with a mean age of (41.8±12.9) years. Most cases (n=80) were treated with one-staged posterior atlantoaxial joint distraction and cage implantation, a few (n=2) underwent ventral decompression. All cases were followed up, postoperative improvement of clinical symptoms and radiology parameters were analyzed. Results: Of the patients, 80 cases (97.6%) received one-staged posterior atlantoaxial joint distraction and cage implantation; lateral facet joint bony fusion was found in 4 patients and was cut off with an osteotome. Transoral odontoidectomy was performed in 2 cases (2.4%) with fused atlanto-odontoid joint. All the patients were followed-up for (18.6±7.3) months. Postoperative CT showed complete reduction of ADI was achieved in 60 patients (75.0%). The ADI decreased significantly after the operation [(2.1±1.4) mm vs (5.0±1.5) mm, P<0.05]. The postoperative vertical distance between odontoid process and the Chamberlain line decreased significantly when compared with that before the operation [(3.9±3.8) mm vs (10.2±5.2) mm, P<0.05]. The mean JOA score at 6 months post operation improved significantly than that before the operation (13.7±1.5 vs 11.2±1.7, P<0.05). Seventy-five patients (93.8%) had atlantoaxial intra-articular bony fusion at 1 year follow-up. Conclusion: Most difficult-reducible atlantoaxial dislocations can be managed well by posterior one-staged atlantoaxial joint distraction and Cage implantation.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Optofluidic system based on electrowetting technology for dynamically tunable spectrum absorber.

An optofluidic system that uses the electrowetting technology to dynamically control the local surface plasmon resonance of the silver nanoparticle is invented. The silver nanoparticle is initially suspended at the interface of the polar liquid and the non-polar liquid. As the interface morphology changes with the applied voltage, the media distribution surrounding particle is changed accordingly, thus realizing the resonance absorption peak's modulation. The investigation result shows that a wide range of the spectral colors from red to blue can be selectively absorbed just by a single device. Specifically, when the radius of the particle is 50 nm, the wavelength of the absorption peak can be dynamically modulated from 460 nm to 607 nm. This proposed method can be used to design and prepare rapidly adjustable optical elements.

[Advances in liver immunology in 2018].

The mechanism of innate and adaptive immune responses to chronic infections with hepatotropic viruses (HBV, HCV) was studied in 2018. Its mechanism elucidated the dysregulation of natural killer (NK) cells, monocytes, B cells and T cells. In addition, a new target for immune regulation of HBV infection (TLR3/OX40L) was introduced. The discovery of new NK cell immune checkpoints, the involvement of mononuclear macrophages in liver failure and inflammation, sex hormone affecting intrahepatic-resistant bacterial infection through the regulation of humoral immunity, and the communication mechanism between liver and other immune organs have enriched people's understanding of liver immunology and its clinical significance.

[Clinical and pathological analysis of renal cell carcinoma bone metastasis].

OBJECTIVE: To analyze the clinical and pathological characteristics of renal cell carcinoma bone metastasis (RCC-BM) patients. METHODS: Data of RCC-BM patients from July 2003 to November 2017 were retrospectively reviewed. The patients' baseline characteristics (age, gender), tumor characteristics [specific sites of bone metastasis, time to bone metastasis (TTBM), imaging features of bone disease, coexistence of other metastasis], as well as pathological features (histological classification of primary and bone metastasis, immunohistochemical stain results) were collected. Descriptive analysis and difference analysis were used. RESULTS: A total of 113 RCC-BM patients were enrolled with the gender ratio (male:female) of 4:1, mean age of 59.39 years, and all present of osteolysis bone lesions. The common sites of bone metastasis were vertebra (46.0%) and pelvis (38.9%). Other distant metastasis sites coexisted in 28.3%, while 48.18% RCC-BM patients presented with synchronous metastasis (TTBM=0). The median TTBM for metachronous metastasis was 48 months. The majority in this cohort were determined to have primary tumor of clear cell carcinoma. After immunohistochemical examination to 104 RCC-BM patients and sub-group analysis, tendencies of higher positive rates of vascular endothelial growth factor (VEGF) was also found in synchronous group (P=0.097) while tendencies of higher positive rates of carbonic anhydrase (CA)-IX was found in the same group (P=0.100). The patients with clear cell RCC-BM had a significantly higher positive expression of epithelial growth factor receptor (EGFR, P<0.05) than those with non-clear cell RCC-BM group. CONCLUSION: More male and younger patients with metastatic lesions in axial skeleton were found in this cohort. Tendencies in the expression of CA-IX and VEGF in different TTBM sub-group and EGFR in different histology-derived subgroup indicate that they might be associated with risk and prognostic factors and support further target therapies of RCC-BM.

[Influence of SOX10 on the proliferation and invasion of prostate cancer cells].

OBJECTIVE: To explore the influence of SOX10 on the proliferation and invasion of prostate cancer cells. METHODS: SOX10 protein in prostate cancer cell lines PC3, DU145 and LNcap was detected by Western blotting analysis. The expression of SOX10 in prostate cancer cell lines (PC3 and DU145) were knocked down by small interfering RNAs, and the efficiency of SOX10 by small interfering RNAs was confirmed using Western blotting analysis. CCK-8 assays were conducted to assess the influences of SOX10 on the proliferation of PC3 and DU145 cells, and invasion assays were conducted to assess the influences of SOX10 on the invasion of PC3 and DU145 cells. RESULTS: After SOX10 in prostate cancer cells was knocked down by small interfering RNAs, the proliferation of prostate cancer cells PC3 and DU145 was significantly inhibited. Results of CCK-8 assays showed that the absorbance of PC3 and DU145 in SOX10-silenced groups was decreased compared with those in control groups (PC3: 0 d: 0.166±0.01, 0.162±0.012 vs. 0.155 ±0.01, P>0.05; 1 d: 0.210±0.011, 0.211±0.018 vs. 0.252±0.023, P>0.05; 2 d: 0.293±0.017, 0.280±0.028 vs. 0.433±0.030, P<0.01; 3 d: 0.363±0.071, 0.411±0.038 vs. 0.754±0.045, P<0.01; 4 d: 0.592±0.065, 0.670±0.093 vs. 1.456±0.111, P<0.01. DU145: 0 d: 0.168±0.018, 0.164±0.01 vs. 0.153 ±0.012, P>0.05; 1 d: 0.218±0.007, 0.206±0.024 vs. 0.255±0.02, P>0.05; 2 d: 0.297±0.013, 0.291±0.012 vs. 0.444±0.023, P<0.05; 3 d: 0.378±0.058, 0.419±0.026 vs. 0.762±0.039, P<0.01; 4 d: 0.681±0.094, 0.618±0.050 vs. 1.419±0.170, P<0.01). Meanwhile, knocking down SOX10 significantly suppressed the invasion of prostate cancer cells PC3 and DU145. Results of invasion assays showed that the numbers of invaded cells in SOX10-silenced groups were significantly less than those in control groups (PC3: 142±38, 171±17 vs. 304±55; DU145: 96±22, 134±23 vs. 341±34, P<0.05). CONCLUSION: SOX10 might promote prostate cancer progression by accelerating the ability of the proliferation and invasion of prostate cancer cells, and SOX10 might be a potential therapeutic target for prostate cancer.

[Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the liver].

Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in the liver and are involved in immunological surveillance of the liver through the expression of various scavenger receptors and pattern recognition receptors. However, in case of several physiological states, viral infections, and tumor environment, liver sinusoidal endothelial cells maintain immune tolerance in the liver through various mechanisms and cause persistent viral infection and tumor metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial cells.

[Effects of trabecular metal augments for the reconstruction of Paprosky type â ¢ acetabulum bone defects].

Objective: To investigate the methods and short-time clinical results of reconstruction of Paprosky type Ⅲ acetabulum bone defects by using tantalum augments. Methods: A total of 17 patients (17 hips) with Paprosky type Ⅲ acetabulum bone defects, treated with tantalum augments in revision of total hip arthroplasty at Department of Orthopedics Surgery in General Hospital of Chinese People's Liberation Army were retrospectively analyzed from March 2014 to May 2016.There were 6 males and 11 females aged from 23 to 74 years with an average of (50.2±16.3) years. Tantalum augments or TM-Cup augment (the cup-on-cup technique) were used to reconstruct the defects.The TM-Cup augment was the tantalum revision cup which was removed titanium ring. The cup-on-cup technique combined TM-Cup augment and biological acetabulum cup. Augments were served as the nonresorptive structural allograft in revision of total hip arthroplasty. Harris hip score was used to evaluate clinical effects. The vertical position of the rotation center was measured and analyzed. Radiographic assessments of the acetabular components were performed by DeLee-Charnley and the Anderson criteria and recorded postoperative complications. Results: All the patients were followed up from 3 to 29 months with an average of (16.2±5.4) months, tantalum augments and biological acetabulum cup were used in 13 patients, the TM-Cup augment and biological acetabulum cup were used in 4 patients. At the time of the latest follow-up, the mean Harris hip score increased compared to preoperatively (86.8±8.3 vs. 30.0±12.0) (t=12.78, P<0.01), the average vertical location of the center of rotation was decreased ((25.3±9.8) mm vs.(47.6±10.5)) mm (t=4.95, P<0.01). All the tantalum augments and biological acetabulum cups were stable, there were no infection, dislocation and other complications. Conclusions: The use of tantalum augments could be considered as an effective management of Paprosky type Ⅲ defects providing good clinical and radiographic outcomes in the short term.The cup-on-cup technique which was used in reconstruction of severe superior-invagination acetabular bone defects and restoration relatively normal center of rotation had special application value.

[Expression of MEK/ERK signal pathways in renal cell carcinoma with bone metastasis].

OBJECTIVE: To investigate the expression of MEK/ERK signaling pathways in renal cell carcinoma with bone metastasis, and to analyze the differences of expressions of VEGFR-2, MEK, ERK on the primary and metastasis tissue and its mechanism. METHODS: The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology, Peking University People's Hospital from January 1, 2009 to January 1, 2010. The expression of MEK/ERK signaling pathways was detected in the 7 renal cell carcinoma patients` primary and matched metastatic tissues with ICH, The antibody concentrations were 1:200, 1:25, and 1:250, respectively. The mutation of the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the second exon of the MEK1 gene were detected with PCR. RESULTS: The expression intensities of VEGFR-2, MEK, and ERK were measured by H-score [intensity (1, 2, 3, or 4) multiplied by the distribution (%)]. VEGFR-2, MEK, and ERK expressions were divided into 3 groups according to the positive distribution of the tumor cells: 1, 0-5%; 2, 6%-50%; and 3, >50%, To assess intratumor heterogeneity, three distinct microscopic fields (×200) from each specimen were used to evaluate the expressions, Subsequently, the scores were averaged to obtain a single concatenated score for each tissue. VEGFR-2, MEK, and ERK expressions were assessed by 2 independent pathologists who were blinded to the clinicopathological data. The data were expressed as the mean value of the triplicate experiments. The expressions of MEK, and ERK were higher in the metastatic tissues than in the matched RCC tissues (6.10±4.10 vs. 1.33±0.51, P=0.015; 9.10±2.24 vs. 4.43± 2.84, P=0.021) while the expression of VEGFR-2 was not different between the primary and metastatic tissues (P=0.901). No mutation was detected on the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the second exon of the MEK1 gene. CONCLUSION: MEK/ERK signaling pathways may play an important role in the metastasis and the resistance of sunitinib in RCC patients with bone metastasis.

[Knockdown of CMTM3 promotes migration and invasion of PC3 cell in vitro].

OBJECTIVE: To investigate the change of biological characteristics after stable knockdown of CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) expression in PC3 by lentivirus shRNA and to reveal new therapeutic targets. METHODS: The research includes two groups: sh393 is the experimental group in which CMTM3 is knocked down in PC3 cell line; shN is the control group in which CMTM3 is negatively knocked down. The expression of CMTM3 was detected by Western blot. The migration ability of PC3 after stable knockdown was detected by Transwell and Wound healing assay. The invasion ability of PC3 was detected by Matrigel assay. RESULTS were obtained from at least three individual experiments. RESULTS: The expression of CMTM3 in sh393 group is significant lower than shN group (0.004 0±0.000 4 vs. 0.490 0±0.055 7, P<0.001) detected by Western blot. It also had statistical significance in Matrigel assays (248.6±4.5 vs. 113.0± 3.3), Transwell (203.6±1.9 vs. 103.0±1.2) and Wound healing assays (95.0±2.9 vs. 33.0±1.5) that knockdown of CMTM3 promoted migration, and invasion of PC3 cells in vitro (P<0.001). CONCLUSION: Negative correlation exists between the stable knockdown of CMTM3 and change of biological characteristics in PC3 cells, and knocking down CMTM3 affects migration, and invasion ability in PC3 cells.

[Expression of MEK/ERK signal pathways in renal cell carcinoma with bone metastasis].

OBJECTIVE: To investigate the expression of MEK/ERK signaling pathways in renal cell carcinoma with bone metastasis, and to analyze the differences of expressions of VEGFR-2, MEK, ERK on the primary and metastasis tissue and its mechanism. METHODS: The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology, Peking University People's Hospital from January 1, 2009 to January 1, 2010. The expression of MEK/ERK signaling pathways was detected in the 7 renal cell carcinoma patients` primary and matched metastatic tissues with ICH, The antibody concentrations were 1:200, 1:25, and 1:250, respectively. The mutation of the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the second exon of the MEK1 gene were detected with PCR. RESULTS: The expression intensities of VEGFR-2, MEK, and ERK were measured by H-score [intensity (1, 2, 3, or 4) multiplied by the distribution (%)]. VEGFR-2, MEK, and ERK expressions were divided into 3 groups according to the positive distribution of the tumor cells: 1, 0-5%; 2, 6%-50%; and 3, >50%, To assess intratumor heterogeneity, three distinct microscopic fields (×200) from each specimen were used to evaluate the expressions, Subsequently, the scores were averaged to obtain a single concatenated score for each tissue. VEGFR-2, MEK, and ERK expressions were assessed by 2 independent pathologists who were blinded to the clinicopathological data. The data were expressed as the mean value of the triplicate experiments. The expressions of MEK, and ERK were higher in the metastatic tissues than in the matched RCC tissues (6.10±4.10 vs. 1.33±0.51, P=0.015; 9.10±2.24 vs. 4.43± 2.84, P=0.021) while the expression of VEGFR-2 was not different between the primary and metastatic tissues (P=0.901). No mutation was detected on the twentieth exon of the PDGFRA gene, the second exon of the K-ras gene, the fifteenth exon of the Braf gene and the second exon of the MEK1 gene. CONCLUSION: MEK/ERK signaling pathways may play an important role in the metastasis and the resistance of sunitinib in RCC patients with bone metastasis.

[Knockdown of CMTM3 promotes migration and invasion of PC3 cell in vitro].

OBJECTIVE: To investigate the change of biological characteristics after stable knockdown of CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) expression in PC3 by lentivirus shRNA and to reveal new therapeutic targets. METHODS: The research includes two groups: sh393 is the experimental group in which CMTM3 is knocked down in PC3 cell line; shN is the control group in which CMTM3 is negatively knocked down. The expression of CMTM3 was detected by Western blot. The migration ability of PC3 after stable knockdown was detected by Transwell and Wound healing assay. The invasion ability of PC3 was detected by Matrigel assay. RESULTS were obtained from at least three individual experiments. RESULTS: The expression of CMTM3 in sh393 group is significant lower than shN group (0.004 0±0.000 4 vs. 0.490 0±0.055 7, P<0.001) detected by Western blot. It also had statistical significance in Matrigel assays (248.6±4.5 vs. 113.0± 3.3), Transwell (203.6±1.9 vs. 103.0±1.2) and Wound healing assays (95.0±2.9 vs. 33.0±1.5) that knockdown of CMTM3 promoted migration, and invasion of PC3 cells in vitro (P<0.001). CONCLUSION: Negative correlation exists between the stable knockdown of CMTM3 and change of biological characteristics in PC3 cells, and knocking down CMTM3 affects migration, and invasion ability in PC3 cells.

[Analysis of metabolic factors and relevance with the grade and stage in patients with renal cell carcinoma].

OBJECTIVE: To investigate the association between metabolic factors, such as obesity, blood pressure, blood glucose, serum lipid profile, and the histopathological characteristics of renal cell carcinoma. METHODS: The medical records of 382 consecutive renal cell carcinoma patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to January 2015 were retrospectively reviewed. Metabolic factors were collected from the records, including weight, body mass index, waist circumstance, blood pressure, fasting blood glucose, serum total triglyceride, serum total cholesterol, serum low-density lipoprotein-cholesterol and serum high-density lipoprotein-cholesterol. The patients were divided into different groups according to tumor grade, stage and diameter. Statistics analysis, such as t test, Mann-Whitney U test and Logistic analysis, were performed to investigate the association between metabolic factors and grade, stage and tumor diameter of renal cell carcinoma. RESULTS: A total of 80 (20.94%) of the tumors were classified as high grade disease, 63 (16.49%) were classified as advanced disease and 153 (40.05%) tumor diameter more than 4 cm. The patients in high grade group were found to have lower high-density lipoprotein-cholesterol level than in low grade group (P=0.015), body mass index, total cholesterol and high-density lipoprotein-cholesterol were found to be lower in advanced disease than in localized disease (P=0.022, P=0.005 and P=0.006, respectively), and low-density lipoprotein-cholesterol was found to be lower in larger tumors (P=0.030). Other factors were comparable between the different groups. The results of Logistic analyses showed that, body mass index (OR=0.906, 95%CI: 0.852-0.986, P=0.023) and total cholesterol (OR=0.660, 95%CI: 0.492-0.884, P=0.005) were associated with the tumor stage, high-density lipoprotein- cholesterol level was significantly associated with tumor grade (OR=0.293, 95%CI: 0.108-0.797, P=0.016) and stage (OR=0.204, 95%CI: 0.065-0.635, P=0.006), and low-density lipoprotein-cholesterol level was significantly associated with tumor diameter (OR=0.756, 95%CI: 0.586-0.975, P=0.031). CONCLUSION: The results of our study indicate that metabolic factors, especially obesity and serum lipid profile, are closely related with the histopathological characteristics of renal cell carcinoma.