Apelin-13 alleviates osteoclast formation and osteolysis through Nrf2-pyroptosis pathway.

Wear particle-induced periprosthetic osteolysis is the key to aseptic loosening after artificial joint replacement. Osteoclastogenesis plays a central role in this process. Apelin-13 is a member of the adipokine family with anti-inflammatory effects. Here, we report that apelin-13 alleviates RANKL-mediated osteoclast differentiation and titanium particle-induced osteolysis in mouse calvaria. Mechanistically, apelin-13 inhibits NLRP3 inflammasome-mediated pyroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In summary, apelin-13 is expected to be a potential drug for relieving aseptic osteolysis. RESEARCH HIGHLIGHTS: This study reveals the molecular mechanism by which apelin-13 inhibits NLRP3 inflammasome activation and pyroptosis by promoting Nrf2. This study confirms that apelin-13 alleviates osteoclast activation by inhibiting pyroptosis. In vivo studies further confirmed that apelin-13 alleviated mouse skull osteolysis by inhibiting the activation of NLRP3 inflammasome.

Influence of sarcopenia on surgical efficacy and mortality of percutaneous kyphoplasty in the treatment of older adults with osteoporotic thoracolumbar fracture.

BACKGROUND: Sarcopenia is an age-related condition that causes loss of skeletal muscle mass and disability. Sarcopenia is closely related to the prognosis of patients suffering osteoporotic thoraco-lumbar compression fractures (OTLCF). The purpose of this study was to investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty (PKP) in the treatment of older adults with OTLCF surgery and postoperative mortality. METHODS: From February 2016 to June 2019, 101 patients who met the inclusion and exclusion criteria were included in this study. The grip strength of the dominant hand was measured using an electronic grip tester. The diagnostic cutoff value of grip strength for sarcopenia was <27 kg for males and <16 kg for females. The cross-sectional area (cm2) of the musculature at the level of the pedicle of the thoracic 12th vertebra (T12) was measured by chest CT. The skeletal muscle index (SMI) was calculated by dividing the muscle cross-sectional area at the T12 pedicle level by the square of the height. The diagnostic cut-off value of SMI at T12 level is 42.6 cm2/m2 for males and 30.6 cm2/m2 for females. Sarcopenia was diagnosed when the grip strength and SMI values were both lower than the diagnostic cut-off value. All included patients received PKP treatment for OTLCF. The age, gender, operation time, bleeding volume, time to ground, length of hospital stay, visual analog scale (VAS) score before operation and one month after operation, Oswestry Disability Index (ODI) one month after operation and the incidence of refracture within 36 months after operation were compared between the two groups. The survival curves of the two groups were analyzed by Kaplan Meier. Chi-square test was used to compare the differences in survival rates between the two groups at 12, 24, and 36 months after operation. Univariate and multivariate Cox regression analysis compared multivariate factors on OTLCF postoperative mortality. RESULTS: There was no significant difference in gender, operation time, blood loss and preoperative VAS score between the two groups (χ2 = 1.750, p = 0.186; t = 1.195, p = 0.235; t = -0.582, p = 0.562; t = -1.513, p = 0.133), respectively. The patients in the sarcopenia group were older (t = 3.708, p = 0.000), and had longer postoperative grounding time and hospitalization time (t = 4.360, p = 0.000; t = 6.458, p = 0.000). The VAS scores and ODI scores one month postoperatively were also higher in sarcopenia group (t = 5.900, p = 0.000; t = 7.294, p = 0.000), and there was a statistical difference between the two groups. Interestingly, there was no significant difference in the incidence of spinal refracture within 36 months between the two groups (χ2 = 1.510, p = 0.219). The sarcopenia group had a higher mortality rate at 36 months after operation, and the difference was statistically significant (p = 0.002). Sarcopenia is an independent risk factor for long-term mortality in OTLCF patients received PKP surgery. CONCLUSIONS: Patients with sarcopenia combined with OTLCF have poor postoperative recovery of limb function and a high risk of death in the long-term (36 months) after surgery. Active and effective intervention for sarcopenia is required during treatment.

Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis.

Joint replacement surgery is the most effective treatment for end-stage arthritis. Aseptic loosening caused by periprosthetic osteolysis is a common complication after joint replacement. Inflammation induced by wear particles derived from prosthetic biomaterials is a major cause of osteolysis. We emphasize that bone marrow-derived macrophages and their fusion-derived osteoclasts play a key role in this pathological process. Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. Aiming at wear particle-induced periprosthetic aseptic osteolysis, this review separately discusses the molecular mechanism of regulation of ROS formation and inflammatory response through intervention of macrophage/osteoclast RANKL-MAPKs-NF-κB pathway. These molecular mechanisms regulate osteoclast activation in different ways, but they are not isolated from each other. There is also a lot of crosstalk among the different mechanisms. In addition, other bone and joint diseases related to osteoclast activation are also briefly introduced. Therefore, we discuss these new findings in the context of existing work with a view to developing new strategies for wear particle-associated osteolysis based on the regulation of macrophages/osteoclasts.

Pyroptosis in Periprosthetic Osteolysis.

Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting in the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts may be the decisive factor. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by gasdermins (GSDMs) family, among which GSDMD is the best characterized. Recent evidence indicates that activation of NLRP3 inflammasomes and pyroptosis play a pivotal role in the pathological process of PPO. Here, we review the pathological process of PPO, the molecular mechanism of pyroptosis and the interventions to inhibit the inflammation and pyroptosis of different cells during the PPO. Conclusively, this review provides theoretical support for the search for new strategies and new targets for the treatment of PPO by inhibiting pyroptosis and inflammation.

Effect of long noncoding RNA NONHSAT070806 on the apoptosis, proliferation, migration, invasion and tumorigenesis of bladder cancer.

Background: Bladder cancer (BC) is the most common malignancy of the urinary tract in China, and the extent of tumor invasion negatively correlates with prognosis. The mechanism of tumor invasion in BC has been unclear until recent studies revealed the critical role of long noncoding RNAs (lncRNAs) in the proliferation and invasion of tumors. Several lncRNAs have been reported to be associated with pathogenesis in BC, but not specifically. Methods: We used a microarray to screen the candidate lncRNAs with different expressions in BC. The expression of the lncRNAs in BC tissues or cells was identified by reverse transcription polymerase chain reaction (RT-PCR) or quantitative real-time PCR (qRT-PCR), and their ectopic expressions were measured via transfection experiment. The function of the lncRNAs was investigated by flow cytometry, caspase-3 enzyme linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8), wound healing, transwell and colony formation experiments in vitro and xenograft experiments in vivo. Results: We identified a novel sense lncRNA, NONHSAT070806, that was downregulated in BC tissues and cells and negatively correlated with level of tumor invasion in patients. Furthermore, overexpression of NONHSAT070806 induced apoptosis of T24 and 5637 cells, inhibited the proliferation, migration and invasion of BC cells, and attenuated the tumorigenesis of BC cells both in vitro and in vivo. Conclusions: NONHSAT070806 may act as a suppressor of BC and is a potential indicator of the invasiveness of BC.

KCC2 overexpressed exosomes meditated spinal cord injury recovery in mice.

Exosomes show great potential in treating diseases of the central nervous system including spinal cord injury (SCI), still better engineered exosomes have more advantages. In this study, we purified exosomes from K+-Cl-co-transporter (KCC2) overexpressed bone marrow mesenchymal stem cells (ExoKCC2), to investigate the effect of ExoKCC2on neural differentiationin vitroand the repairing function of ExoKCC2in SCI micein vivo. Compared to bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exo), ExoKCC2could better promote neural stem cell differentiated into neurons, ameliorate the function recovery of SCI mice, and accelerate the neural regeneration at the lesion site. Altogether, engineered ExoKCC2may prove to be an advantageous strategy for SCI treatment.

Effects of supplemental ferulic acid (FA) on survival, growth performance, digestive enzyme activities, antioxidant capacity and lipid metabolism of large yellow croaker (Larimichthys crocea) larvae.

A 30-day feeding trial was conducted to investigate the effects of supplemental ferulic acid (FA) on survival, growth performance, digestive enzyme activities, antioxidant capacity and lipid metabolism of the large yellow croaker larvae (initial weight: 2.58 ± 0.30 mg). Four isonitrogenous and isolipidic micro-diets were formulated with graded levels of FA (0, 20, 40, and 80 mg/kg) and fed to the experimental larvae seven times daily. Results showed that larvae fed the diet with 40 mg/kg FA had significantly higher survival rate, while the specific growth rate was higher in larvae fed diets with 40 and 80 mg/kg FA than the control group (P < 0.05). Activities of trypsin in pancreatic segments (PS) and intestinal segments, lipase in PS and alkaline phosphatase in brush border membrane were significantly increased by supplementation of FA compared to the control group (P < 0.05). Supplementation of FA significantly increased activities of total superoxide dismutase and catalase, and reduced the malondialdehyde content compared to the control group (P < 0.05). Meanwhile, activities of lysozyme, total nitric oxide synthase and nitric oxide content were significantly improved by supplemental FA in diets. Furthermore, supplementation of 40 mg/kg FA reduced the triglyceride content in larval visceral mass probably through down-regulating expression of lipogenesis-related genes (scd1, fas and dgat2) and up-regulating expression of lipid catabolism-related genes (aco, cpt-1 and hl). In conclusion, appropriate supplementation of 40 mg/kg FA could improve the survival and growth performance of large yellow croaker larvae through increasing digestive function, antioxidant capacity and promoting lipid metabolism.

Effect of the degree of displacement of the third fragment on healing of femoral shaft fracture treated by intramedullary nailing.

OBJECTIVE: To investigate the effect of the degree of displacement of a femoral shaft fracture with the third fragment on fracture healing after intramedullary nailing. METHODS: In total, 216 patients with closed comminuted femoral fracture admitted to Lianyungang Hospital affiliated to Xuzhou Medical University from February 2010 to February 2016 were analyzed retrospectively. Among these patients, 142 were males and 74 were females, the mean age was 38 years (range 17-64 years), and 95 cases were on the right, while 121 cases were on the left. All patients were treated with a femoral interlocking intramedullary nail. Referring to the femoral shaft diameter, the degree of displacement of the third fragment was classified into four grades: grade I (displacement was less than a third of the diameter of the shaft): 121 cases; grade II (greater than a third of the diameter and less than two thirds): 52 cases; grade III (greater than two thirds of the diameter): 28 cases; and grade IV (fracture fragment turnover): 15 cases. According to the modified Radiological Union Scale for Femur (mRUSF), the fracture union rate and the mean union time of the fracture, the effect of the degree of displacement of the third fragment on fracture healing was evaluated. RESULTS: In total, 216 patients with a mean follow-up of 15.9 months (range 6-31 months) met the inclusion criteria. The best fracture healing was the grade I displacement, with a union rate of 89.2% and a mean union time of 7.7 months. The poorest fracture healing was for the grade IV displacement, with a union rate of 13.3% and a mean union time of 16.5 months. The healing was moderate in the grade II and III displacements, with a union rate of 46.2% and 28.6%, respectively, and a mean union time of 8.6 months and 13.5 months, respectively (P < 0.05). CONCLUSIONS: The third fragment with grade I displacement requires no intervention, whereas fractures with grade IV displacement should be reduced to as near as possible to the diaphyseal bone defect to avoid nonunion. The third fragments with the grade II or III displacement should be treated with closed reduction whenever possible to achieve a displacement within the range of grade I to minimize the incidence of nonunion.

Nutritional programming of large yellow croaker (Larimichthys crocea) larvae by dietary vegetable oil: effects on growth performance, lipid metabolism and antioxidant capacity.

The nutritional status experienced in the early development of life plays a vital role in the long-term metabolic state of the individual, which is known as nutritional programming. The present study investigated the long-term effects of vegetable oil (VO) nutritional programming during the early life of large yellow croaker. First, larvae were fed either a fish oil (FO) diet or a VO diet for 30 d. Subsequently, under the same conditions, all fish were fed a commercial diet for 90 d and thereafter challenged with an FO or VO diet for 30 d. The results showed that growth performance was significantly lower in larvae fed the VO diet than in those in fed the FO diet in the stimulus phase. Notably, VO nutritional history fish showed lower levels of liver lipids liver total triglycerides and serum nonesterified free fatty acids than the FO nutritional history fish when juveniles were challenged with the VO diet, which was consistent with the expression of lipogenesis-related genes and proteins. Moreover, the VO nutritional history fish showed lower liver damage and higher antioxidant capacity than FO nutritional history fish when challenged with the VO diet. In summary, this study showed that a short VO stimulus during the early life stage of large yellow croaker, had a long-term effect on lipid metabolism and the antioxidant system. Specifically, VO nutritional programming had a positive effect on alleviating abnormal lipid deposition on the liver, liver damage, and the reduction of hepatic antioxidant capacity caused by a VO diet.

Effects of dietary eucommia ulmoides leaf extract on growth performance, expression of feeding-related genes, activities of digestive enzymes, antioxidant capacity, immunity and cytokines expression of large yellow croaker (Larimichthys crocea) larvae.

A 30-d feeding trial was conducted to investigate effects of dietary eucommia ulmoides leaf extract (ELE) on growth performance, activities of digestive enzymes, antioxidant capacity, immunity, expression of inflammatory factors and feeding-related genes of large yellow croaker larvae. Five micro-diets were formulated with supplementation of 0 g kg-1 (the control), 5 g kg-1 (0·5 %), 10 g kg-1 (1·0 %) and 20 g kg-1 (2·0 %) of ELE, respectively. Results showed that the best growth performance was found in larvae fed the diet with 1·0 % ELE. Furthermore, ELE supplementation significantly increased the npy expression at 1·0 % dosage, while increased ghrelin in larvae at 0·5 % dosages. The activity of leucine aminopeptidase in larvae fed the diet with 1·0 % ELE was significantly higher than the control, while alkaline phosphatase was significantly upregulated in larvae fed the diet with 2·0 % ELE. A clear increase in total antioxidant capacity in larvae fed the diet with 1·0 % ELE was observed, whereas catalase activity was significantly higher in 1·0 % and 2·0 % ELE supplementation compared with the control. Larvae fed the diet with 1·0 % ELE had a significantly higher activities of lysozyme, total nitric oxide synthase and nitric oxide content than the control. Moreover, transcriptional levels of cox-2, il-1ß and il-6 were remarkably downregulated by the supplementation of 0·5-1·0 % ELE. This study demonstrated that the supplementation of 1·0 % ELE in diet could increase the growth performance of large yellow croaker larvae probably by promoting expression of feeding-related genes, enhancing antioxidant capacity and immunity and inhibiting expression of inflammatory factors.

Effects of surgical approaches and morphological characteristics on the follow up outcomes of patients with posterolateral tibial plateau fractures.

This study aimed to study the effects of surgical approaches and identify the morphological characteristics associated with the 1-year follow-up outcome of patients with posterolateral tibial plateau fractures after successful surgery.We followed 200 postoperative patients for 1 year. The modified Hospital for Special Knee Surgery score (HSS score) was used to evaluate the functional recovery of the knee. We supposed 4 morphological characteristics in CT images acting as possible risk factors, including the anteroposterior diameters of posterolateral broken bone fragments (fragment-diameter), the damage to the posterolateral cortex of the tibial head (cortex-damage), the combinational fracture of the proximal fibula (fibula-fracture) or fracture of the medial tibial condyle (medial-condyle-fracture). Multivariate regression models were used to analyze the effect of these factors on the HSS score after adjusting the 2 surgical approaches and other confounders.The average HSS score was 85.1 ±â€Š5.8 for all the patients. We treated 155 patients with the anterolateral approach and 45 patients with the posterolateral approach. The surgical approach, fragment-diameter, fibula-fracture, and medial-condyle-fracture were correlated with the HSS scores (P < .05). After adjusting for the above factors, the Schatzker type, age and gender, compared with anterolateral approach, the posterolateral approach could improve the HSS scores by an average of 3.7 points. The fragment-diameter <20 mm and posterolateral approach interacted on the HSS scores. Comparing posterolateral and anterolateral approaches, we found that the HSS scores of patients with fragment-diameter <20 mm increased by 6.1 points (95% CI: 4.1-8.2) in the posterolateral approach, while those with fragment-diameter ≥20 mm did not significantly improve the HSS scores.The surgical approach, fragment-diameter, fibula-fracture, and medial-condyle-fracture were independent risk factors associated with the follow-up outcome of patients with posterolateral tibial plateau fractures after successful surgery. The posterolateral approach could significantly improve the HSS score in the studied hospital.

Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis.

Proinflammatory macrophage (M1) is now being suggested as a potential therapeutic strategy for cancer because of its tumoricidal capacity. However, few studies have been focused directly on the effects of M1 macrophages on cancer cells. Here, we found that M1 induced a subpopulation of CD44high/CD24-/low or ALDH1+ cells with CSC-like phenotypes from different types of breast cancer cells (BCCs) in a paracrine manner. Stat3/NF-κB pathways in BCCs were activated by proinflammatory cytokines, igniting Lin-28B-let-7-HMGA2 axis to induce CSC through epithelial-mesenchymal transition (EMT). Previously, we reported that Stat3-coordinated Lin-28B-let-7-HMGA2 axis initiated EMT in BCCs. Here, inhibition of Stat3/NF-κB pathways or Lin-28B-let-7-HMGA2 axis suppressed EMT/CSCs program. Notably, HMGA2 knockdown directly repressed M1-induced CSC formation and expression of Klf-4 and Nanog. Meanwhile, prolonged coculture with BCCs endowed M1 with M2 properties. M1 supernatant induced CSC from non-stem cancer cells, while M2 supernatant sustained a higher proportion of ALDH1+ cells. Our data suggest that macrophages might modulate CSC formation and maintenance by transferring between M1/M2 phenotype. Given that M1 are being considered as a promising immunotherapy tool, it is important to inhibit their CSC-inducing potential by targeting key molecules and pathways.

MYC upregulated LINC00319 promotes human acute myeloid leukemia (AML) cells growth through stabilizing SIRT6.

Long non-coding RNAs (lncRNAs) have been identified by accumulating studies as critical regulator in tumorigenesis and tumor development in human cancers, including in acute myeloid leukemia (AML). This study investigated the function and the underlying mechanism of LINC00319 in AML progression. Firstly, the low expression level of LINC00319 in whole blood of healthy individuals was obtained from UCSC, and its upregulation was detected in AML patients as well as AML cell lines. Besides, the prognostic significance of LINC00319 was revealed in AML patients. Functionally, the loss-of-function assays revealed that LINC00319 silence restrained proliferation but stimulated apoptosis in AML cells. Furthermore, LINC00319 expression was demonstrated proportional to MYC level in AML samples and transcriptionally regulated by MYC. Mechanistically, we identified FUS as a shared RNA binding protein (RBP) interacting with both LINC00319 and SIRT6. And LINC00319 regulated SIRT6 expression at post-transcriptional level through FUS-dependent pathway. Last but not least, SIRT6 overexpression rescued the suppressive effect of LINC00319 knockdown on AML cells growth. Overall, our findings unveiled that LINC00319 contributed to AML leukemogenesis via elevating SIRT6 expression, indicating a possible molecular target of LINC00319 for AML treatment.

Comparison of hook plate with versus without double-tunnel coracoclavicular ligament reconstruction for repair of acute acromioclavicular joint dislocations: A prospective randomized controlled clinical trial.

PURPOSE: This study was designed to compare the surgical outcomes of a hook plate with double-tunnel coracoclavicular (CC) ligament reconstruction by conjoined tendon transfer versus single hook plate surgery for the repair of acute type of Rockwood type III and V acromioclavicular (AC) joint dislocations. METHODS: The study cohort included 62 patients with acute (within 6 weeks after trauma) Rockwood type III and V AC joint dislocations who underwent surgery from February 2012 to September 2015. The patients were randomly allocated to the ligament reconstruction group (LR group, n = 31) or the single hook plate group (HP group, n = 31). In both groups, reduction of the AC joint by hook plate and repair of the ruptured AC ligament with absorbable Vicryl sutures were performed homoplastically. The lateral half of the short tendon of the biceps brachii muscle and the lateral half of the flexor tendon were used to reconstruct the trapezoid and conoid ligaments, respectively. Differences in surgical duration, intraoperative blood loss, incision length, and total cost were compared between the two groups. Furthermore, the preoperative and postoperative visual analogue score (VAS), postoperative American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score (CMS), Karlsson score, complication rates, and patient satisfaction at the last follow-up were compared to evaluate the curative effects of the surgical treatments. Magnetic resonance imaging (MRI) after hook plate removal was used to evaluate the reconstructed ligaments and tendon-bone interface. RESULTS: In total, 25 patients in the LR group and 26 in the HP group completed the follow-up. There were no statistically significant differences in age, sex, Rockwood type, placing time, total cost, and follow-up duration between the LR and HP groups (p > 0.05). However, as compared with the HP group, the surgical duration and incision length were longer in the LR group (92.08 ±â€¯19.25 vs. 56.54 ±â€¯21.29 min and 13.64 ±â€¯0.90 vs. 6.65 ±â€¯1.01 cm, respectively, p < 0.05). In addition, there was no significant difference in preoperative VAS scores, but the postoperative VAS score was lower in LR group than in the HP group (2.52 ±â€¯1.19 vs. 4.12 ±â€¯1.45, respectively, p < 0.05). Moreover, patients in LR group had a remarkable higher CMS and ASES score (89.56 ±â€¯2.80 vs. 79.31 ±â€¯4.97 and 92.60 ±â€¯2.79 vs. 82.35 ±â€¯3.44, respectively, p < 0.05). The overall excellent or good result rate, as evaluated by the Karlsson score, was 92.00% (23/25) and 50.00% (13/26), respectively (p < 0.05). MRI findings revealed good condition of the reconstructed ligaments and tendon-bone interface. The incidence of complications was lower and the satisfaction rate was higher in the LR group than in the HP group (1/25 vs. 16/26 and 23/25 vs. 14/26, respectively, p < 0.05). CONCLUSIONS: The overall surgical effect of the use of a hook plate combined with double-tunnel CC ligament reconstruction is superior to single hook plate surgery for the repair of acute Rockwood type III and V AC joint dislocations.

[Establishment of mouse model of bone metastasis of prostate cancer and breast cancer via femoral artery injection of tumor cells].

OBJECTIVE: To explore an efficient and reliable method for establishing an animal model of bone metastasis of tumors. METHODS: Male C57BL/6J mice were randomized into 4 equal groups to receive injections of normal saline or prostate cancer RM-1 cell suspension via the femoral artery or the external iliac artery, and breast cancer 4T1-luc cells were injected in 15 female BALB/c mice via the femoral artery. The operation time, postoperative survival rate, and the tumor formation rates in the mice with two different injection methods were compared. The tumor metastasis in the mice was evaluated with in vivo imaging. RESULTS: The mean time for hemostasis time was 2.53∓1.75 min in mice receiving tumor cell injection via the femoral artery, significantly shorter than that in mice with injections via the external iliac artery (4.70∓1.63 min; P<0.05); the mean operation time was 14.67∓2.16 min and 22.47∓3.50 min in the two groups, respectively (P<0.05). At 21 days after the operation, the survival rate was 93.3% in femoral artery injection group, significantly higher than that in external iliac artery injection group (66.7%;P<0.05). The tumor metastasis rate was 100% in both groups. CONCLUSION: Injection of the tumor cells via the femoral artery is more suitable for establishing mouse models of bone metastasis of cancers.

[Establishment of a human bladder cancer cell line stably co-expressing hSPRY2 and luciferase genes and its subcutaneous tumor xenograft model in nude mice].

Objective To establish a human bladder cancer cell line stably co-expressing human sprouty2 (hSPRY2) and luciferase (Luc) genes simultaneously, and develop its subcutaneous tumor xenograft model in nude mice. Methods The hSPRY2 and Luc gene segments were amplified by PCR, and were cloned into lentiviral vector pCDH and pLVX respectively to produce corresponding lentivirus particles. The J82 human bladder cancer cells were infected with these two kinds of lentivirus particles, and then further screened by puromycin and G418. The expressions of hSPRY2 and Luc genes were detected by bioluminescence, immunofluorescence and Western blot analysis. The screened J82-hSPRY2/Luc cells were injected subcutaneously into BALB/c nude mice, and the growth of tumor was monitored dynamically using in vivo fluorescence imaging system. Results J82-hSPRY2/Luc cell line stably expressing hSPRY2 and Luc genes was established successfully. Bioluminescence, immunofluorescence and Western blot analysis validated the expressions of hSPRY2 and Luc genes. The in vivo fluorescence imaging system showed obvious fluorescence in subcutaneous tumor xenograft in nude mice. Conclusion The J82-hSPRY2/Luc bladder cancer cell line and its subcutaneous tumor xenograft model in nude mice have been established successfully.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Prostate Cancer: A Systematic Review and Meta-analysis.

Inflammation is increasingly reported to be associated with the prognosis of patients with cancers. And the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa) remains inconsistent. Therefore, we conducted this systematic review and meta-analysis to obtain a more reliable assessment of prognostic significance of NLR in PCa.A comprehensive literature research regarding the association of NLR and prognosis of PCa was performed through PubMed, Embase, Cochrane Central, and Web of Science. The hazard ratios (HRs) and its 95% confidence intervals (CIs) for overall survival (OS), progression-free survival, or recurrence-free survival were extracted and pooled using fix-effects model or random-effects model.A total of 14 studies that met our criterion were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was not significantly associated with the poor OS (HR = 1.45; 95% CI 0.77-2.71; P = 0.248) or recurrence-free survival (HR = 1.34; 95% CI 0.89-2.02; P = 0.155) of patients with localized PCa. Although elevated NLR predicted poorer OS (HR = 1.57; 95% CI 1.41-1.74; P < 0.001) and progression-free survival (HR = 1.97; 95% CI 1.28-3.04; P = 0.002) of patients with metastatic castration resistant prostate cancer (mCRPC).Elevated NLR is a strong indicator of poorer prognosis of patients with mCRPC, whereas the NLR is not significantly associated with prognosis of patients with localized PCa. Therefore, NLR could be used in patients with mCRPC for risk stratification and decision making of individual treatment.

Lateroconal fascia suspension for management of peritoneal tear and "curtain" effect during retroperitoneal laparoscopic operations.

PURPOSE: To describe the method of lateroconal fascia suspension for the management of peritoneal tear and curtain effect during retroperitoneal laparoscopic operations. MATERIALS AND METHODS: Between May 2013 and October 2014, we performed lateroconal fascia suspension in 30 cases of retroperitoneal laparoscopic operations. Peritoneal tear occurred and retroperitoneal space collapsed in 18 cases of them during the operation, and free edge of the lateroconal fascia caused curtain effect and sheltered the field of view in another 12 cases after the lateroconal fascia was incised longitudinally. RESULTS: The curtain effect of lateroconal fascia was eliminated successfully, and the sheltered field of view got normal in all the 12 cases. The collapsed retroperitoneal space due to peritoneal tear got enlarged effectively and was sufficient for the following operations in 15 patients of the overall 18 cases, while the collapsed retroperitoneal space did not get enlarged significantly in the other three cases. After the insertion of an extra 5-mm trocar into peritoneal space, the collapsed retroperitoneal space got enlarged eventually. Finally, retroperitoneal laparoscopic operations were continued and completed successfully in all these 30 patients. It took 4 min to complete the suspension procedure, and no related complications occurred during the whole suspension process. CONCLUSION: Lateroconal fascia suspension method could manage most peritoneal tears and curtain effect effectively during retroperitoneal laparoscopic operations.

Radiofrequency Ablation Versus Partial Nephrectomy in Treating Small Renal Tumors: A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) has emerged as an alternative treatment to surgical partial nephrectomy (PN) in the treatment of small renal tumors (SRTs). But its safety and oncological efficacy are still controversial. We conducted this systematic review and meta-analysis to compare the peritoperative and oncological outcomes of RFA and PN in the treatment of SRTs. Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science were searched to identify eligible studies that compared the RFA and PN in the treatment of SRTs. Twelve retrospective studies that compared RFA with PN in the treatment of SRTs met our selection criterion and were included in this meta-analysis. The pooled results indicated that the local recurrence rate (4.14% vs 4.10%, RR: 1.18, 95% CI: 0.68, 2.07, P = 0.550) and distant metastases rate (2.76% vs 1.89%, RR: 1.31, 95% CI: 0.70, 2.46, P = 0.686) were not significantly different between the RFA group and the PN group. In terms of perioperative outcomes, RFA was associated with shorter length of stay (LOS) (WMD: -2.02 days, 95% CI: -2.77, -1.27, P < 0.001), lower eGFR decline after treatment (WMD: -3.90, 95% CI: -6.660, -1.140, P = 0.006). However, the overall perioperative complication rate (7.5% vs 6.2%, RR:1.10, 95% CI: 0.64, 1.87, P = 0.740) and the major complication rate (3.7% vs 4.4%, RR: 0.83, 95% CI: 0.43, 1.60, P = 0.579) were both similar between RFA and PN groups. Compared with PN, RFA achieves an equal oncological outcome for SRTs with similar local recurrence rate and distant metastases rate. Additionally, RFA is associated with a similar perioperative complication rate, lower decline of eGFR, and shorter LOS. Therefore, RFA is an effective option in the treatment of SRTs for selected patients.