Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects.In order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ability.Furthermore,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apa with reducing dosage for combinational gastric therapy.Thus,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchro-nously transport the two drugs into tumor tissue.In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs adminis-tration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects.In summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.

Objective:To explore the predictive value of the systemic immune inflammation index (SII) for the risk of bone metastases in patients with newly diagnosed prostate cancer (PCa).Methods:From Jun. 2012 to Jul. 2019, the clinical features of 308 patients were retrospectively analyzed. For the baseline clinical data of the patients with newly diagnosed PCa, the median age was 71(65-76) years, there were 59(19.2%) patients with a positive digital rectal examination (DRE). In addition, the median serum total prostate-specific antigen (tPSA), prostate volume (PV) and prostate-specific antigen density(PSAD)were 60.55(23.55-100.00) ng/ml, 39.35(28.29-56.66)ml and 1.27(0.58-2.52)ng/(ml·cm 3), respectively. There were 33(10.7%)patients with prostate biopsy Gleason score≤6, 115(37.3%)patients with a Gleason score=7 and 160(52.0%)patients with a Gleason score≥8. The T clinical stage also obtained, including 21(6.8%)diagnosed as T 1 stage, 87(28.2%)T 2 stage, 65(21.1%)T 3stage, 135(43.9%)T 4 stage. SII was calculated by the formula platelet×neutrophil/lymphocyte, and the median(interquartile range)of SII was 458.60(300.42-727.11)/L. According to the results of bone scanning, the patients were divided into bone metastasis(146, 47.4%)and a non-bone metastasis groups(162, 52.6%). The differences in the baseline clinical characteristics between the two groups were analyzed. The risk factors of bone metastasis were analyzed by univariate and multivariate logistic regression analysis. The diagnostic efficiency of the risk factors were evaluated by receiver operating characteristic(ROC)curve. Results:The median(interquartile range)of SII was 564.78/L(333.85-961.93/L)in patients with bone metastasis which were higher than those without bone metastasis 413.01(267.63-601.79)/L( P<0.001). The median(interquartile range)of tPSA were 97.79(48.20-119.10)ng/ml in bone metastasis group and 32.56(17.89-72.70)ng/ml in non-bone metastasis group ( P<0.001). The median(interquartile range)of PSAD were 1.91(0.97-3.55)ng/(ml·cm 3)and 0.90(0.45-1.77)ng/(ml·cm 3)in these two groups( P<0.001), respectively. In bone metastasis group, there were 132(90.4%)patients with a positive DRE, yet there were only 117(72.2%) patients with a positive DRE in the other group ( P<0.001). There were 7(4.8%)patients with prostate biopsy Gleason score≤6, 50(34.2%)patients with a Gleason score=7 and 89(61.0%)patients with a Gleason score≥8 in bone metastasis group. There were 26(16.1%)patients with prostate biopsy Gleason score≤6, 65(40.1%)patients with a Gleason score=7 and 71(43.8%)patients with a Gleason score≥8 in non-bone metastasis group ( P<0.001). There were statistically significant difference between the two groups in T clinical stage( P<0.001). In bone metastasis group, there were 2(1.4%)T 1 stage, and 19(13.0%)T 2 stage, 25(17.1%)T 3stage, and 100(68.5%)T 4 stage. Comparatively, there were 19(11.7%)T 1 stage, 68(42.0%)T 2 stage, 40(24.7%)T 3stage, and 35(21.6%)T 4 stage in the other group. There were no statistically significant difference between the two groups in term of age( P=0.057) and TPV( P=0.222). Univariate and multivariate logistic regression analysis showed that tPSA( P=0.003), SII( P<0.001), T clinical stage( P<0.001)could be regarded as independent risk factors of bone metastasis of PCa. Area under the curve of SII+ tPSA was 0.770, which was higher than SII(0.653)or tPSA(0.729) alone( P<0.05). When the cut-off value was 727.72/L, the sensitivity and specificity of the diagnosis of SII alone were 38.4% and 87.7%. The sensitivity and specificity of tPSA alone were 67.1%and 75.9% when the cut-off value was 73.02ng/ml. The sensitivity was 72.6% and the specificity was 71.6% when SII and tPSA was combined. Conclusions:SII is an independent predictor of bone metastasis of newly diagnosed with PCa. , and the patients were at high risk when SII exceeded 727.72/L. The combination of SII and tPSA can improve its predictive validity for the risk of bone metastasis.

Squamous cell carcinoma (SCC) of the renal pelvis is extremely rare and hardly to be diagnosed due to its lack of specificity in clinical manifestations and traditional imaging features. We reported a case with history of multiple operations for double kidney stones, who was admitted to our hospital twice due to "right kidney ureteral stones, left kidney complex stones, chronic renal insufficiency and urinary tract infection" . During this period, a total of 6 surgeries were performed. In the first 19-day hospitalization, right transurethral ureteroscopic lithotripsy and right percutaneous nephroscope lithotripsy(PCNL)were performed respectively. And 20 days later, the patient was admitted to hospital again for management of left complex kidney stones, and the left side PCNL was performed for 4 times within 27 days. During the two hospitalizations, no tumor was reported during the three times of contrast-enhanced CT examination of the urinary system. The patient continued to have fever after the 4th time of left PCNL, with failure of anti-infection treatment. Then, the of the left renal pelvis was considered clinically, and left nephrectomy was suggested after communication with the patient and his family members. Postoperative pathology confirmed renal pelvis SCC. After surgery, the patient’s temperature was back to normal and then discharged. The patient died 3 months after discharging due to the systemic metastasis.

To identify risk factors for early complications in patients after robot-assisted laparoscopic radical cystectomy (RARC) and a standardized reporting model to predict complications precisely and recommend reasonable prophylaxis.
 Methods: A total of 90 patients with bladder cancer, who underwent RARC in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2016 to January 2018, were enrolled for this study. Their clinical information, preoperative examination and follow-up data within 90 d after RARC were collected. Univariable and multivariable logistic regressions were performed to identify risk factors for early complications after RARC.
 Results: The overall incidence of complications within 90 d after RARC was 48.9% (44/90), including 9 cases of Clavien grade 1, 17 cases of Clavien grade 2, 4 cases of Clavien grade 3, 12 cases of Clavien grade 4, and 2 cases of Clavien grade 5. Acute renal injury (22.2%), intestinal obstruction (16.7%), urinary tract infection (14.4%) and lymphatic leakage (10.0%) were the most common complications within 90 d after the operation. Two patients (2.2%) died within 90 d after the operation. Preoperative BMI (OR=1.16, 95% CI 1.02 to 1.32), postoperative instant (≤30 min) serum creatinine (OR=1.02, 95% CI 1.00 to 1.03), and pT stage (OR=1.67, 95% CI 1.05 to 2.68) were the risk factors for early complications after RARC. 
 Conclusion: The incidence of early complications after RARC is high. Preoperative hemodialysis, correction of anemia, intraoperative protection of renal function, and early recovery after surgery are helpful to prevent early complications after RARC.
Cystectomy ; Humans ; Laparoscopy ; Postoperative Complications ; Risk Factors ; Robotic Surgical Procedures ; Robotics ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery

Objective To evaluate the prognostic value of pretreatment neutrophil to lymphocyte ratio (NLR) on prostate cancer patients treated with maximal androgen blockade (MAB).Methods The clinical data of 249 prostate cancer patients treated with MAB in our hospital from October 2007 to March 2017 were retrospectively analyzed.Among all the patients,the median age was 72 years old (ranged 48 to 89 years).The BMI was 14.5-31.8kg/m2 (median 23.0 kg/m2).The PSA was 1.00-758.21 ng/ml (median 60.04 ng/ml).216 patients' tumor invaded surrounding tissues;lymph node metastasis occurred in 157 patients;and distant organ metastasis occurred in the remaining 174 patients.The Gleason score was 3-10 (median 7).Copfimary end points were progression-free survival (PFS) and cancer-specific survival (CSS).The best cutoff value of NLR was calculated by receiver operating characteristic (ROC) curve.The prognostic analysis of NLR on prostate cancer patients treated with MAB was estimated using Cox proportional hazards models and Kaplan-Meier analysis.Results The ideal cutoff value of the pretreatment NLR was 2.29 (95％ CI 0.603-0.737,P ＜0.001) determined by the ROC curve according to the survived and deceased cases at the end point of CSS,by which the 249 patients was divided into the high NLR group of 119 patients (47.8％) and the low NLR group of 130 patients (52.2％).High NLR was significantly associated with high Gleason score (P =0.019),higher clinical T stage (P =0.001),N stage (P ＜ 0.001),M stage (P ＜ 0.001) and more neutrophil count (P ＜ 0.001).The median follow-up time was 29 months (ranged 5 to 124).During this period,115 patients died,and the whole fatality rate was 46.2％.40 patients died in low NLR group (30.8％),while the figures for the high NLR group were 75 (63.0％).Kaplan-Meier analysis demonstrated that patients with NLR ≥ 2.29 had a poor outcome both in PFS (P ＜ 0.001) and CSS (P ＜ 0.001).The multivariate Cox analysis showed that NLR,Gleason score,clinical TNM stage and ECOG score were independent predictors for PFS and CSS.Conclusion Pretreatment NLR could be an independent prognostic biomarker for PFS and CSS in prostate cancer patients undergoing MAB.

Objective:To present our initial experience with robot-assisted laparoscopic prostatectomy (RALP) for complicated cases.Methods:Clinical and pathological data from 4 complicated prostate cancer cases,who underwent RALP from October to November in 2015,were analyzed retrospectively.All the cases were conducted transurethral plasmakinetic enucleation of prostate and hormonal therapy before RALP.Results:All surgeries were done successfully.The age,baseline prostatic special antigen,clinical tumor stage,operation time and estimated blood loss were 58-70 years,6.04-70.15 ng/mL,T2bT3b,210-360 min and 50-250 mL,respectively.No blood transfusion was needed.All surgical margin were negative.Conclusion:Although previous transurethral surgeries and hormonal therapies may increase the difficulty for operations,RALP is still appropriate for the complicated cases of prostate cancer.

OBJECTIVE: To explore the expression of perforin and granzyme-B in peripheral blood lymphocyte (PBL) in patients with prostate cancer (PCa) and the clinical significance. METHODS: The expressions of perforin and granzyme-B in PBL were detected by fluorescence quantitative reverse transcription polymerase chain reaction. The results of perforin and granzyme-B expression were compared among patients with PCa (n=60), patients with BPH (benign prostatic hyperplasia, n=40) and healthy controls (n=20). RESULTS: Th e expressions of perforin and granzyme-B in patients with PCa were significantly lower than that in patients with BPH or that in the healthy controls (P<0.05), respectively. Furthermore, in PCa patients with low pathological grade, the expressions of perforin and granzyme-B in PBL was statistically higher than that in patients with high pathological grade (P<0.05). The expressions of perforin and granzyme-B in PCa patients at high clinical stage was statistically lower than that in PCa patients at low clinical stage (P<0.05). CONCLUSION The results of this study suggest that development and progression of PCa might be associated with poor immune status of patients.
Case-Control Studies ; Granzymes ; metabolism ; Humans ; Lymphocytes ; enzymology ; Male ; Perforin ; metabolism ; Prostatic Hyperplasia ; Prostatic Neoplasms ; immunology

We reviewed and analyzed the clinical data for a patient with metastatic castration-resistant prostate cancer (mCRPC) from September, 2009 to December, 2014. After the treatment with abiraterone, patient's performance status improved, pain relieved, total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) markedly decreased. tPSA or fPSA fluctuated between 
30 and 50 ng/mL or between 10 and 20 ng/mL. MRI showed the left peripheral zone reduced. MRI and bone single photon emission computed tomography (SPECT) scan showed no new metastasis. These results indicated that application of abiraterone for patient with mCRPC not only decreased prostate specific antigen (PSA) levels and tumor volume, but also blocked bone metastasis progression and enhanced pain relief.
Androstenes ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Disease Progression ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology

Objective: To investigate the clinical effect of total cystectomy and W-shaped orthotopic ileal neobladder for bladder cancer. Methods: Total cystectomy and W-shaped orthotopic ileal neobladder were performed on 29 male patients and 3 female patients. Atfer the cystectomy, 35-40 cm terminal ileal segment was isolated to make W-shaped orthotopic ileal neobladder. Bilateral uretero-ileal anastomoses were constructed by nipple technique, urethral stump was sutured to the lowest portion of the ileal pouch. Results: All surgeries were completed successfully. Patients were able to void by increasing the abdominal pressure, daytime continence rate was 87.5% and nighttime continence rate was 78.1%. The mean neobladder capacity was 410.6 mL and the mean postvoid residual urine was22.7 mL at 6 months. After the surgery, ileal neobladder leakage occurred in 3 (9.4%) patients, mild ileus occurred in 2 (6.3%) patients, ileo-urethral anastomosis stricture developed in 1(3.1%) patient, and dysuria occurred in 3 (9.4%) patients because of the mucus.HTe complications were treated properly and satisfactory results were obtained. Erection was preserved in 5 of the 9 male patients with normal erectile function, and normal sexual function was preserved in 1 female patient who underwent uterus-sparing cystectomy. HTe mean follow-up was 15 months.One patient died of distant metastasis and pneumonia, while other patients survived without tumor. Conclusion: Total cystectomy and W-shaped orthotopic ileal neobladder have the advantages of voiding through the native urethra, satisfactory continence, low complication rates of upper urinary tract damage and electrolyte imbalance. W-shaped orthotopic ileal neobladder may be considered as the ifrst option of urinary diversion atfer cystectomy. Postoperative management should focus on complications and follow-up.

Objective:To construct a p53-fused dual luciferase reporter and to test whether this reporter can mimic wild-type p53 activities in a high-throughput screen.Methods:A restriction endonuclease site was added to each terminus and the stop codon of the wild-type full-length p53 open reading frame (ORF) was removed by PCR. A restriction endonuclease site was added to each terminus and the start codon of the ifrelfy luciferase ORF was removed by PCR. The two modified ORFs were inserted upstream of the IRES-induced renilla luciferase ORF in a CMV-derived vector. hTe p53 fusion protein was expressed in cells to test its MDM2-mediated degradation, subcellular localization, and induction of p53-responsive promoter.
Results:hTe p53-fused dual luciferase reporter was successfully constructed. Atfer transfection into the host cells, the reporter expressing the p53 fusion protein that was degraded by oncoprotein MDM2, was mainly located inside the nucleus, and induced the p53-responsive promoter, respectively.
Conclusion:hTe p53-fused dual luciferase reporter (p53FL/IRES/RL) can identify modulators of P53 protein level in a high-throughput screen of genetic or chemical libraries.