Electrocardiographic characteristics of bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy.

OBJECTIVE: Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations. METHODS: Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab-paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP. RESULTS: A total of 60 patients (76.7% males), including 30 muscle-invasive and 30 non-muscle-invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019). CONCLUSION: In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long-term follow-up.

Puerarin inhibits the development of osteoarthritis through antiinflammatory and antimatrix-degrading pathways in osteoarthritis-induced rat model.

Puerarin is an isoflavone isolated from the medicinal plant Pueraria lobata. The purpose of this study was to study the antiinflammatory and antimatrix-degrading effects of puerarin in a rat osteoarthritis (OA) model and its protective effects on joints. The rat OA model was established by anterior cruciate ligament transection (ACLT) surgery. Rats (n = 40) were divided into nontreated OA, OA + celecoxib (2.86 mg/kg), OA + puerarin (50 and 100 mg/kg), and control groups. Two weeks after surgical induction, puerarin was administered by gavage daily for 8 weeks. After 8 weeks, macroscopic observation and histopathological images showed that cartilage damage was reduced after puerarin and celecoxib treatment, the intensity of Safranin O staining was high, and the OARSI scores were significantly reduced compared to the OA group. Puerarin reduced the expression of MMP-3, MMP-13, ADAMTS-5, and COX-2 in the cartilage tissue of ACLT rats, inhibited the production of IL-1ß, IL-6, and TNF-α inflammatory factors, increased Type II collagen content, and altered the expression of serum OA cartilage degradation/bone turnover biomarkers (CTX-I, CTX-II, COMP, and PIINP). Based on these findings, we speculate that puerarin supplement to attain recovery from OA damage.

Ni Hierarchical Structures Supported on Titania Nanowire Arrays as Efficient Nonenzymatic Glucose Sensor.

Developing new advanced nonenzymatic electrochemical nano-sensors for glucose detection has attracted intensive attraction. In this work, we designed a novel nanocomposite nonenzymatic glucose sensor by fabricating hierarchically nanostructured metal nickel on titania nanowire arrays, which was loaded on a transparent conductive substrate (i.e., fluorine-doped tin oxide, FTO) surface by mild hydrothermal method. Due to the large surface area of the hierarchically nanostructured Ni and fast electron transfer of the TiO2 nanowire arrays electrode, the nanocomposite electrode shows excellent electrochemical activity toward the oxidation of glucose. The electrode exhibits high sensitivity in detecting glucose concentration (1472 µA mM-1 cm-2) with a wide linear range from 2×10-4 M to 2×10-3 M, fast response time (within 5 s), and small detection limit (10 µM) (S/N = 3). The good analytical performance, low cost and simple preparation method make this novel electrode material promising for the development of effective glucose nonenzymatic glucose sensor.

KIF5A Promotes Bladder Cancer Proliferation In Vitro and In Vivo.

BACKGROUND: Bladder cancer is a common malignancy with uncontrolled and rapid growth. Although lots of the important regulatory networks in bladder cancer have been found, the cancer-relevant genes remain to be further identified. METHODS: We examined the KIF5A expression levels in bladder cancer and normal bladder tissue samples via immunohistochemistry and observed the effect of KIF5A on bladder tumor cell proliferation in vitro and in vivo. Additionally, a coexpression between KIF5A and KIF20B in tumor tissues was explored. RESULTS: KIF5A expression level was higher in the bladder cancer tissues than in the adjacent nontumor tissues. Patients with higher KIF5A expression displayed advanced clinical features and shorter survival time than those with lower KIF5A expression. Moreover, KIF5A knockdown inhibited bladder cancer cell proliferation, migration, and invasion demonstrated in vivo and in vitro. In addition, coexpression was found between KIF5A and KIF20B in tumor tissues. CONCLUSION: The results demonstrated that KIF5A is a critical regulator in bladder cancer development and progression, as well as a potential target in the treatment of bladder cancer.

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer.

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

RAB38 promotes bladder cancer growth by promoting cell proliferation and motility.

BACKGROUND: Bladder cancer is the most common malignancy of urinary system with high morbidity and mortality. In general, the development and progression of bladder cancer are complicated pathological processes, and the treatment methods mainly include surgical resection, radiotherapy, chemotherapy, and combined therapy. In recent years, targeted therapy has made progress in the treatment of bladder cancer. Therefore, to improve survival rates of patients with advanced bladder cancer, novel therapeutic targets are still urgently needed. METHODS AND RESULTS: In this study, we found that RAB38 expressed in tumor tissues of patients with bladder cancer was linked to clinical features including pTNM stage and tumor recurrence, and positively correlated with the poor prognosis of bladder cancer. Notably, further results indicated that depletion of RAB38 could significantly inhibit the proliferation and motility of two types of human bladder cancer cells, T24 and 5637 cells. In addition, RAB38 ablation obviously blocked tumor growth and development in mice compared with control. CONCLUSION: In conclusion, this study provides significant evidence that RAB38 promotes the development of bladder cancer and provides a novel therapeutic target of bladder cancer.

Largely Enhanced Mobility in Trilayered LaAlO3/SrTiO3/LaAlO3 Heterostructures.

LaAlO3 (LAO)/SrTiO3 (STO)/LaAlO3 (LAO) heterostructures were epitaxially deposited on TiO2-terminated (100) SrTiO3 single-crystal substrates by laser molecular beam epitaxy. The electron Hall mobility of 1.2 × 104 cm2/V s at 2 K was obtained in our trilayered heterostructures grown under 1 × 10-5 Torr, which was significantly higher than that in single-layer 5 unit cells LAO (∼4 × 103 cm2/V s) epitaxially grown on (100) STO substrates under the same conditions. It is believed that the enhancement of dielectric permittivity in the polar insulating trilayer can screen the electric field, thus reducing the carrier effective mass of the two-dimensional electron gas formed at the TiO2 interfacial layer in the substrate, resulting in a largely enhanced mobility, as suggested by the first-principle calculation. Our results will pave the way for designing high-mobility oxide nanoelectronic devices based on LAO/STO heterostructures.

Orientation-dependent structural and photocatalytic properties of LaCoO3 epitaxial nano-thin films.

LaCoO3 epitaxial films were grown on (100), (110) and (111) oriented LaAlO3 substrates by the polymer-assisted deposition method. Crystal structure measurement and cross-section observation indicate that all the LaCoO3 films are epitaxially grown in accordance with the orientation of LaAlO3 substrates, with biaxial compressive strain in the ab plane. Owing to the different strain directions of CoO6 octahedron, the mean Co-O bond length increases by different amounts in (100), (110) and (111) oriented films compared with that of bulk LaCoO3, and the (100) oriented LaCoO3 has the largest increase. Photocatalytic degradation of methyl orange indicates that the order of photocatalytic activity of the three oriented films is (100) > (111) > (110). Combined with analysis of electronic nature and band structure for LaCoO3 films, it is found that the change of the photocatalytic activity is closely related to the crystal field splitting energy of Co3+ and Co-O binding energy. The increase in the mean Co-O bond length will decrease the crystal field splitting energy of Co3+ and Co-O binding energy and further reduce the value of band gap energy, thus improving the photocatalytic activity. This may also provide a clue for expanding the visible-light-induced photocatalytic application of LaCoO3.

Prognostic significance of urothelial carcinoma with divergent differentiation in upper urinary tract after radical nephroureterectomy without metastatic diseases: A retrospective cohort study.

To evaluate the impact of urothelial carcinoma with divergent differentiation (UCDD) on the prognosis of patients for primary upper urinary tract urothelial carcinoma (UTUC) with pN0/x status treated with radical nephroureterectomy (RNU) and to evaluate the prognostic value of UCDD in different tumor locations (renal pelvis and ureter).Data from a total of 346 patients with UTUC who received RNU between January 2012 and March 2016 in the institution were retrospectively analyzed. Clinicopathological features and prognostic factors age, sex, complaint, height, weight, blood pressure, tumor grade, stage, smoking status, history of adjuvant chemotherapy, tumor location, history of bladder cancer, tumor necrosis, degree of hydronephrosis, tumor size, tumor focality, and preoperative anemia were compared between patients with pure UTUC and patients with UCDD. The endpoints were cancer-specific survival (CSS), overall survival (OS), and intraluminal recurrence-free survival (IRFS).Overall, divergent differentiation was present in 50 patients (14.5%). UCDD was related to different tumor location (P = .01), smoking (P = .04), higher body mass index (P = .02), and advanced tumor grade (P = .01). By Kaplan-Meier analysis, UCDD was found to be significantly correlated with worse IRFS, CSS, and OS (all P < .01). Multivariate analysis demonstrated that UCDD was an independent predictor of IRFS (P < .01), CSS (P = .01), and OS (P = .01). However, 40 patients died for various reasons and the 5-year OS rates were 91.9% in UCDD- group and 68.0% in UCDD+ group, respectively. In patients with ureteral tumors, UCDD was the significant predictor for IRFS, CSS, and OS. However, the prognostic value of UCDD was not observed in pyelocaliceal tumors.The presence of divergent differentiation is associated with inferior survival. UCDD may identify patients at high risks for poor prognosis especially in patients with ureteral tumors. As a result, more attention and follow-up should be given to patients with ureteric urothelial carcinoma.

Biological effects of eukaryotic recombinant plasmid pReceiver-M61-BAI-1 transfection on T24 cells and HUVECs.

The aim of the current study was to investigate the biological effect on T24 cells and human umbilical vein endothelial cells (HUVECs) of transfection with brain-specific angiogenesis inhibitor-1 (BAI-1). The recombinant plasmid pReceiver-M61-BAI-1 was transfected into human superficial bladder tumor cells (T24) and HUVECs, in parallel with the vector control. mRNA and protein expression levels of BAI­1 were then detected by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. Cell apoptosis of T24 cells and HUVECs prior and subsequent to transfection with BAI­1 was analyzed by flow cytometric analysis. Proliferation of T24 cells and HUVECs prior and subsequent to transfection of BAI-1 was assessed by the MTT method. T24 cells and HUVECs transfected with pReceiver­M61­BA1­1 were classed as the experimental group; T24 cells and HUVECs transfected with p­Receiver­M61 were the control group. qPCR and western blotting methods confirmed that there was positive expression of BAI­1 in T24 cells and HUVECs transfected with pReceiver­M61­BAI­1, however BAI­1 was not expressed in T24 cells and HUVECs transfected with pReceiver­M61. The results of the MTT assay demonstrated that absorbance was markedly reduced in HUVECs at 12, 48 and 72 h subsequent to transfection with pReceiver-M61-BAI-1 when compared with that of the control group and in T24 cells transfected with p­Receiver-M61-BAI-1. Furthermore, flow cytometry results also indicated that the apoptotic rate of HUVECs transfected with p­Receiver­M61­BAI­1 was significantly increased compared with that of the control group and T24 cells transfected with p­Receiver­M61­BAI­1. BAI­1 was observed to markedly inhibit the proliferation of vascular endothelial cells in vitro, however, no direct inhibition by BAI­1 was observed in T24 cells. In conclusion, BAI-1 is suggested to be a potential novel therapautic target for the inhibition of tumor neovascularization.

Subtle Interplay between Localized Magnetic Moments and Itinerant Electrons in LaAlO3/SrTiO3 Heterostructures.

Clarification of the role of magnetic ordering and scattering in two-dimensional electron gas has become increasingly important to understand the transport and magnetic behavior in the LaAlO3 (LAO)/SrTiO3 (STO) heterostructures. In this work, we report the sheet resistance of the LAO/STO heterostructures as functions of temperature, magnetic field, and field orientation. An unexpected resistance minimum was discovered at ∼10 K under a sufficiently high in-plane magnetic field. An anisotropic magnetoresistance (MR) is clearly identified, indicating the presence of magnetic scattering which may be related to the interaction between itinerant electrons and localized magnetic moments in the LaAlO3/SrTiO3 heterostructures. It is believed that the high concentration of oxygen vacancies induced by the ultralow oxygen partial pressure during the deposition process plays a predominant role in the occurrence of the anisotropic MR.

The evaluation of the association between the metabolic syndrome and tumor grade and stage of bladder cancer in a Chinese population.

OBJECTIVE: The objective of this article was to summarize the relationship between some components of metabolic syndrome (MetS) and the histopathologic findings in bladder cancer in a Chinese population. METHODS: We retrospectively analyzed data of 323 patients from the Department of Urology, Second Hospital of Tianjin Medical University between January 2012 and January 2014. All the patients were diagnosed with bladder cancer for the first time. Age, height, weight, histologic stage, grade, the presence of hypertension, diabetes mellitus, and body mass index were evaluated. The 2009 American Joint Committee on Cancer TNM staging system was used, with Ta and T1 tumors accepted as lower stage and T2, T3, and T4 tumors as higher stage bladder cancers. Also, pathologists assigned tumor grade according to the 1973 World Health Organization grading system. Noninvasive papillary urothelial neoplasms of low malignant potential were regarded as low grade. Analyses were completed using chi-square tests and logistic regression analysis. RESULTS: Of the 323 patients, 164 had hypertension, 151 had diabetes mellitus, and 213 had a body mass index ≥25 kg/m(2). MetS was significantly associated with histologic grade (P<0.001) and stage (P=0.006) of bladder cancer. Adjusted for age in binary logistic regression analysis, the presence of MetS predicts the risk of higher T stage (odds ratio =4.029, P<0.001) and grade (odds ratio =3.870, P<0.001) of bladder cancer. CONCLUSION: The patients with MetS in the People's Republic of China were found to have statistically significant higher T stage and grade of bladder cancer.

A giant pelvic malignant schwannoma: a case report and literature review.

Schwannomas are usually benign tumors that arise from well-differentiated Schwann cells. They rarely occur in the retroperitoneum. Here, we present a case of a 60-year-old man with a giant retroperitoneal pelvic mass. Imageological diagnosis suggested a large heterogeneous mass of 16 cm in diameter located in the abdominopelvic retroperitoneum. Complete intralesional enucleation was achieved without any adjacent organs injury except a severe bleeding which was ceased as we applied the bilateral inferior vesical artery embolization. Final histopathological result showed the tumor was a low malignant Schwannoma. The patient's symptoms were greatly improved after operation. Unfortunately, a local recurrence was detected at the six-month follow-up appointment with consequent losing to follow up.

[Diagnosis and treatment of xanthogranulomatous prostatitis: a case report and review of the literature].

OBJECTIVE: To explore the diagnosis and treatment of xanthogranulomatous prostatitis. METHODS: A 75-year-old man presented with a 3-month history of difficult urination and frequent micturition, which was exacerbated for 2 days. Digital rectal examination indicated an enlarged prostate size of II degrees with hard texture but no tenderness. Serum total PSA was 172.5 microg/L. TRUS revealed 200 ml of post-micturition residual urine, thickened bladder wall, prostate size of 4.3 cm x 3.8 cm x 5.0 cm and no isochrones. MRI showed an enlarged prostate gland, with marked enlargement of the central zones and low-signal intensity of the peripheral gland, part of the prostate gland protruding to the bladder with no clear dividing line. It was diagnosed as prostate cancer initially, and confirmed by needle biopsy. RESULTS: Histopathological examination revealed large numbers of "foamy macrophages" in the lesion, with a few multinucleated giant cells, leukocytes, mononuclear, plasmocytes and fibroplasia. Immunohistochemistry showed CD68 (+) and PSA (-). The patient was treated with oral Tamsulosin and glucocorticoid and by temporary catheterization, and followed up for 20 months. Urination symptoms began to alleviate and serum PSA to decrease at 4 months. The PSA level was 9.2 microg/L at 13 months and 3.6 microg/L at 17 months. CONCLUSION: Xanthogranulomatous prostatitis is a rare clinically, which can be confirmed by histopathological examination. It is treated mainly by supportive therapy and, for the cases with severe lower urinary tract obstruction, TURP can be employed. Follow-up must be performed by possible examination of PSA and necessary needle biopsy of the prostate.

[The concentration of HO-2 and CO in rat penile tissue of different ages].

OBJECTIVE: To compare the distribution of heme oxygenase-2 and concentration of carbon monoxide in rat penile tissue of 8, 16 and 24 months and investigate the relationship between the system of HO-2/CO and aging. METHODS: Using SABC immunohistochemistry staining, image analysis system and the method of carboxyhemoglobin standard curve, the distribution of heme oxygenase-2 and concentration of carbon monoxide in different month rat penile tissues were investigated. RESULTS: The penile arteries were surrounded by HO-2 positive cells, which were also seen in the trabecular meshwork of smooth muscle. Compared with other part of penile, the penile arteries adventitia and the endothelial cells of cavernous exhibited darker staining. With the increasing of rat's living month the staining of penile tissues turned faint and the concentration of carbon monoxide in tissue decreased( P < 0.05 ). The imaging analysis system showed that the older the rat was the less HO-2 positive compositions contained (P < 0.05). CONCLUSION: With aging the decreasing concentration of HO-2 leads to the downfgt-regulation in rat penile tissue.