Bladder paraganglioma: basic characteristics and new perspectives on perioperative management.

PURPOSE: Paraganglioma and pheochromocytoma are rare neuroendocrine tumors with severe metabolic and cardiovascular complications. Bladder PGLs are rare, and their clinical management is not precise. Here, we discuss the basic characteristics and perioperative management of bladder PGLs. METHODS: We retrospectively reviewed 20 bladder PGL cases diagnosed at Sun Yat-sen University Cancer Center. Case notes were reviewed, clinical presentations, therapies, and outcomes were collected, and data analysis was performed. RESULTS: Ten male and ten female patients with a median age of 47.5 years (range 14-69 years) were included. Most patients (65%) had no symptoms, and PGL was detected incidentally during medical checkups. All patients were treated surgically; 4 (20%) underwent transurethral resection of bladder tumor (TURBT), and 16 (80%) underwent partial cystectomy. Strong intraoperative blood pressure fluctuations were observed in 13 patients (65%). Two patients who were treated preoperatively with α-receptor blockers also experienced severe intraoperative blood pressure fluctuations. Postoperative measurements of troponin I were available for 3 patients, and all were significantly elevated. All patients were diagnosed with bladder PGL on postoperative pathological examination. The median follow-up time was 51 months (range 2-147 months), and 2 patients were lost to follow-up at 1 and 3 months; 16 (88.9%) survived without recurrence, 2 patients (11.1%) experienced recurrence, and 1 patient died. CONCLUSION: Most bladder paragangliomas are easily mistaken for bladder urothelial carcinoma, and robust hemodynamic instability during surgery might be a challenge for urologists. Postoperative monitoring of troponin I, regardless of the presence of clinical symptoms, is recommended for patients with bladder PGL.

Molecular Biomarker of Drug Resistance Developed From Patient-Derived Organoids Predicts Survival of Colorectal Cancer Patients.

The drug 5-fluorouracil (5-Fu) is the critical composition of colorectal cancer (CRC) treatments. Prognostic and predictive molecular biomarkers for CRC patients (CRCpts) treated with 5-Fu-based chemotherapy can provide assistance for tailoring treatment approach. Here, we established a molecular biomarker of 5-Fu resistance derived from colorectal cancer organoids (CRCOs) for predicting the survival of CRCpts. Forty-one CRCO cultures were generated from 50 CRC tumor tissues after surgery (82%). The following experiments revealed a great diversity in drug sensitivity for 10 µM 5-Fu treatment tested by using organoid size change. Fourteen cases (34.1%) were 5-Fu sensitive and the other 27 (65.9%) were resistant. Then, differentially expressed genes (DEGs) associated with 5-Fu resistance were outputted by transcriptome sequencing. In particular, DEGs were generated in two comparison groups: 1) 5-Fu sensitive and resistant untreated CRCOs; 2) CRCOs before 5-Fu treatment and surviving CRCOs after 5-Fu treatment. Some molecules and most of the pathways that have been reported to be involved in 5-Fu resistance were identified in the current research. By using DEGs correlated with 5-Fu resistance and survival of CRCpts, the gene signature and drug-resistant score model (DRSM) containing five molecules were established in The Cancer Genome Atlas (TCGA)-CRC cohort by least absolute shrinkage and selection operator (LASSO) regression analysis and 5-fold cross-validation. Multivariate analysis revealed that drug-resistant score (DRS) was an independent prognostic factor for overall survival (OS) in CRCpts in TCGA-CRC cohort (P < 0.001). Further validation results from four Gene Expression Omnibus (GEO) cohorts elucidated that the DRSM based on five genes related to 5-Fu chemosensitivity and developed from patient-derived organoids can predict survival of CRCpts. Meanwhile, our model could predict the survival of CRCpts in different subgroups. Besides, the difference of molecular pathways, tumor mutational burden (TMB), immune response-related pathways, immune score, stromal score, and immune cell proportion were dissected between DRS-high and DRS-low patients in TCGA-CRC cohort.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer.

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l-1 with a sensitivity of 60.0% and a specificity of 67.8%. In the validation set, the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging (MRI) (0.619 vs 0.238, P < 0.001). The nomogram involving PMC, free prostate-specific antigen (fPSA), clinical T stage, preoperative Gleason score, and monocyte-to-lymphocyte ratio (MLR) was generated, which showed a robust predictive capacity for predicting LNM before the operation. Our results indicated that PMC as a single agent, or combined with other clinical parameters, showed a robust predictive capacity for LNM in PCa. It can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

The Surface Characteristics, Microstructure and Mechanical Properties of PEEK Printed by Fused Deposition Modeling with Different Raster Angles.

Additive manufacturing provides a novel and robust way to prepare medical product with anatomic matched geometry and tailored mechanical performance. In this study, the surface characteristics, microstructure, and mechanical properties of fused deposition modeling (FDM) prepared polyether-ether-ketone (PEEK) were systematically studied. During the FDM process, the crystal unit cell and thermal attribute of PEEK material remained unchanged, whereas the surface layer generally became more hydrophilic with an obvious reduction in surface hardness. Raster angle has a significant effect on the mechanical strength but not on the failure mechanism. In practice, FDM fabricated PEEK acted more like a laminate rather than a unified structure. Its main failure mechanism was correlated to the internal voids. The results show that horizontal infill orientation with 30° raster angle is promising for a better comprehensive mechanical performance, and the corresponding tensile, flexural, and shear strengths are (76.5 ± 1.4) MPa, (149.7 ± 3.0) MPa, and (55.5 ± 1.8) MPa, respectively. The findings of this study provide guidelines for FDM-PEEK to enable its realization in applications such as orthopedic implants.

Risk-adapted treatment reduced chemotherapy exposure for clinical stage I pediatric testicular cancer.

BACKGROUND: Different from adult clinical stage I (CS1) testicular cancer, surveillance has been recommended for CS1 pediatric testicular cancer. However, among high-risk children, more than 50% suffer a relapse and progression during surveillance, and adjuvant chemotherapy needs to be administered. Risk-adapted treatment might reduce chemotherapy exposure among these children. METHODS: A decision model was designed and calculated using TreeAge Pro 2011 software. Clinical utilities such as the relapse rates of different groups during surveillance or after chemotherapy were collected from the literature. A survey of urologists was conducted to evaluate the toxicity of first-line and second-line chemotherapy. Using the decision analysis model, chemotherapy exposure of the risk-adapted treatment and surveillance strategies were compared based on this series of clinical utilities. One-way and two-way tests were applied to check the feasibility. RESULTS: In the base case decision analysis of CS1 pediatric testicular cancer, risk-adapted treatment resulted in a lower exposure to chemotherapy than surveillance (average: 0.7965 cycles verse 1.3419 cycles). The sensitivity analysis demonstrated that when the relapse rate after primary chemotherapy was ≤ 0.10 and the relapse rate of the high-risk group was ≥ 0.40, risk-adapted treatment would result in a lower exposure to chemotherapy, without any association with the proportion of low-risk patients, the relapse rate of the low-risk group, the relapse rate after salvage chemotherapy or the toxicity utility of second-line chemotherapy compared to first-line chemotherapy. CONCLUSIONS: Based on the decision analysis, risk-adapted treatment might decrease chemotherapy exposure for these high-risk patients, and an evaluation after orchiectomy was critical to this process. Additional clinical studies are needed to validate this statement.

AICAR and Decitabine Enhance the Sensitivity of K562 Cells to Imatinib by Promoting Mitochondrial Activity.

Although the advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the survival of patients with chronic myeloid leukaemia (CML), acquired drug resistance and TKI-insensitive leukaemic stem cells (LSCs) remain major obstacles to a CML cure. In recent years, the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers, including CML, and in turn may be exploited for therapeutic purposes. Here, we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide (AICAR) and decitabine could effectively increase the ATP content and mitochondrial biogenesis. In addition, these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation. Moreover, we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity of K562 cells to imatinib, as evidenced by a combination treatment assay. Altogether, our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.

High PRMT5 expression is associated with poor overall survival and tumor progression in bladder cancer.

Arginine methyltransferase 5 (PRMT5) is involved in a variety of cancers. We used bioinformatics analysis to investigate PRMT5 overexpression in bladder urothelial cancer (BUC) and its clinical significance. We also conducted molecular biology experiments to investigate the effect of PRMT5 on the phenotype of BUC cells in vitro and in vivo. PRMT5 was found to be upregulated in BUC tissue in the Oncomine and The Cancer Genome Atlas databases. We validated the results from these databases in a cohort of BUC samples. Kaplan-Meier and Cox multivariate analyses demonstrated that PRMT5 upregulation is an independent prognostic risk factor for BUC. The in vitro and in vivo phenotypic experiments found that downregulated expression of PRMT5 in BUC cells inhibits BUC cell proliferation and aggression. In addition, gene set enrichment analysis demonstrated that PRMT5 knockdown leads to cell cycle G1/S arrest, deactivation of Akt, and mTOR phosphorylation in BUC cells. These results suggest that PRMT5 could be used as a potential molecular marker for BUC in the future.

MAP kinase-interacting kinase 1 (MNK1) plays as a tumor suppressor in bladder cancer.

BACKGROUND: MAP kinase-interacting kinase 1 (MNK1) has been reported to be over-expressed in several cancers, however, its expression level and biological function in bladder cancer (BCa) remains unclear. METHODS: Besides analyzing human publicly available dataset, we used quantitative real-time PCR, western blotting and immunohistochemistry to evaluate the expression of MNK1 in BCa and the adjacent normal bladder epithelial tissues. In vitro and in vivo proliferation assays including cell counting kit-8 and xenograft assay were carried out to explore the role of MNK1 in BCa. Chi-square test and Cox proportional hazards regression model were performed to describe MNK1's clinical significance in BCa patients. RESULTS: Compared to normal bladder epithelia, MNK1 was down-regulated in the clinical tumor specimens and cell lines of BCa both at mRNA and protein level. MNK1 expression was found significantly associated with advanced T status and poor overall survival (OS) of BCa patients who had received radical cystectomy and was an independent prognostic biomarker for OS. Biological function assays demonstrated that MNK1 could impair the proliferation capacities of BCa cell lines both in vivo and in vitro. CONCLUSIONS: Unlike other cancers, MNK1 is low-expressed in BCa tissues and could inhibit the proliferation ability of BCa cells, which suggests that MNK1 might play as a tumor suppressor in BCa.

The interaction of tumor cells and myeloid-derived suppressor cells in chronic myelogenous leukemia.

Myeloid-derived suppressor cells (MDSCs) are considered to be a strong contributor to the immunosuppressive tumor microenvironment. In our study, the counts of MDSCs were correlated with the remission status of CML patients, especially the M-MDSCs. M-MDSCs promoted the proliferation of K562 cells or CD34+ cells from newly diagnosed CML patients, no matter in cells or mice experiments. We also established a TKI discontinuation model using the K562 cell line for examining the effect of microvesicles (MVs) derived from K562 cells before and after TKI discontinuation on MDSCs. We found a mutual promotion of proliferation of tumor cells and MDSCs. Moreover, MVs derived from K562 cells after TKI discontinuation significantly improved the proliferation of MDSCs compared with MVs from before TKI discontinuation. The bidirectional interaction results in a vicious cycle, by providing a protective niche against immune attacks. Therapeutic interventions modulating this interaction might accelerate the success of TFR.

Conservative treatment for urinary fistula following ileal conduit urinary diversion: a simple method.

BACKGROUND: The presence of urinary fistula after ileal conduit urinary diversion is a challenging complication, and this study investigated the role of the intra-conduit negative pressure system (NPS) in the presence of urinary fistula following ileal conduit (IC) urinary diversion as a conservative treatment. METHODS: Using the intra-conduit NPS, a minor drainage tube was placed within a silicon tube to suck urine from the conduit with consistent negative pressure. Patients with urinary fistula following IC from August 2012 to July 2017 were recorded, and the clinical characteristics and outcome were retrospectively analyzed. RESULTS: The intra-conduit NPS was used as a primarily conservative treatment for 13 patients who suffered from urinary fistula and presented with a large amount of abdominal/pelvic drainage without other significant morbidities. The median age was 60 years old (42-74 years), and 7patients were male. The median duration between the IC operation and the presence of urinary fistula was 15 days (2-28 days), and elevated creatinine levels were detected in the abdominal/pelvic drainage with a median level of 2114 µmol/L (636-388 µmol/L). A significant decrease in abdominal/pelvic drainage was identified in 12 patients. The median time that the NPS was used was 9 days (7-11 days). The other patient did not show any improvements after 2 days of observation and then underwent open surgery. With ureteral stenting, 2 abdominal drainage tubes and the intra-conduit NPS were placed during operation, no urine leakage was observed in the abdominal/pelvic field, and the patient was cured in 9 days. With a median follow-up of 22 months, no fistula recurrence or hydronephrosis was detected. CONCLUSION: The intra-conduit negative pressure system is a feasible and promising way to cure urinary fistula following ileal conduit urinary diversion. Because this procedure is a mini-invasive and simple approach, it might represent an alternative in selected patients.

Understanding optical reflectance contrast for real-time characterization of epithelial precursor lesions.

Detecting early-stage epithelial cancers and their precursor lesions are challenging as lesions could be subtle and focally or heterogeneously distributed over large mucosal areas. Optical coherence tomography (OCT) that enables wide-field imaging of subsurface microstructures in vivo is a promising screening tool for epithelial diseases. However, its diagnostic capability has not been fully appreciated since the optical reflectance contrast is poorly understood. We investigated the back-scattered intensities from clustered or packed nanometer scale intracellular scatterers using finite-difference time-domain method and 1-µm resolution form of OCT, and uncovered that there existed correlations between the reflectance contrasts and the ultrastructural clustering or packing states of these scatterers, which allows us to interpret the physiological state of the cells. Specifically, both polarized goblet cells and foveolar cells exhibited asymmetric reflectance contrast, but they could be differentiated by the optical intensity of the mucin cup due to the different ultrastructural make-ups of the mucin granules; keratinocytes could demonstrate varied cytoplasmic intensity and their cytoplasmic contrast was closely correlated with the packing state of keratin filaments. Further preliminary study demonstrated that these new understandings of OCT image contrast enables the characterization of precancerous lesions, which could complement the current morphology-based criteria in realizing "virtual histology" and would have a profound impact for the screening and surveillance of epithelial cancers.

Geometry-Dependent Spectroscopic Contrast in Deep Tissues.

Nano-structures of biological systems can produce diverse spectroscopic effects through interactions with broadband light. Although structured coloration at the surface has been extensively studied, natural spectroscopic contrasts in deep tissues are poorly understood, which may carry valuable information for evaluating the anatomy and function of biological systems. Here we investigated the spectroscopic characteristics of an important geometry in deep tissues at the nanometer scale: packed nano-cylinders, in the near-infrared window, numerically predicted and experimentally proved that transversely oriented and regularly arranged nano-cylinders could selectively backscatter light of the long wavelengths. Notably, we found that the spectroscopic contrast of nanoscale fibrous structures was sensitive to the pressure load, possibly owing to the changes in the orientation, the degree of alignment, and the spacing. To explore the underlying physical basis, we further developed an analytical model based on the radial distribution function in terms of their radius, refractive index, and spatial distribution.

A clinicopathological analysis of adrenal tumors in patients with history of extra-adrenal cancers.

BACKGROUND: Adrenal tumors in patients with previous/synchronous extra-adrenal malignancy are diverse and are a dilemma in clinical practice. This study investigated the differentiation of adrenal malignant and benign tumors in these patients. METHODS: Data from patients with a pathological diagnosis of adrenal tumors were retrospectively retrieved from April 1991 to November 2015. Patients without extra-adrenal malignancy were excluded. Clinical and imaging characteristics, including sex, age, tumor size, tumor location, isolated lesion, time interval between the diagnosis of the two tumors and retrieved imaging diagnosis, were collected and analyzed. The selected patients were divided into 2 groups: those with primary or secondary malignancies (PSM) and those with primary benign tumors (PB). Chi-squared tests were used to evaluate differences between the two groups. Logistic regression was performed to explore potential risk factors related to the differentiation of PSM and PB, and a receiver operating characteristic (ROC) curve was used to evaluate their diagnostic values. RESULTS: Ninety-one patients were selected; 54 were male, and the median age was 56 years old. Between the groups of PSM and PB, sex (p = 0.004), age (p = 0.029), tumor size (p < 0.001), isolated lesion (p < 0.001) and imaging diagnosis (p < 0.001) were significantly different, while tumor size (p = 0.001), sex (p = 0.047) and imaging diagnosis (p = 0.002) were independent predictors of PSM. With ROC curve analysis, risk factors ≥2 was the optimal cutoff to differentiate these adrenal tumors, and their sensitivity and specificity were 73 and 77%, respectively. With a median follow-up of 32 months, only 4 of 32 patients with PB died from cancer, and 24 of 47 patients with PSM died from cancer, although aggressive treatment was performed. CONCLUSIONS: Tumor size, sex and imaging diagnosis were independent predictors of adrenal primary or secondary malignancies. These predictors might be helpful for differentiation of adrenal tumors in patients with previous/synchronous extra-adrenal cancers.

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial-mesenchymal transition via Akt/GSK3ß signaling.

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real-time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin-embedded BC tissues displayed that upregulated expression of KIFC1 clearly correlated with pT status (P = .014) and recurrent status (P = .002). Kaplan-Meier survival analysis and log-rank test indicated that patients with BC with high KIFC1 expression had both shorter cancer-specific survival (P < .001) and recurrence-free survival time (P < .001) than those with low KIFC1 expression. Furthermore, ectopic downregulation of KIFC1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC1 enhanced this in vitro. Overexpression of KIFC1 phosphorylated GSK3ß and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial-mesenchymal transition (EMT) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC1 to promote BC cell proliferation and EMT via Akt/GSK3ß signaling; KIFC1 might be a promising prognostic biomarker as well as a therapeutic target for BC.

[Microplastic Pollution of the Beaches in Xiamen Bay, China].

Microplastics are tiny ubiquitous plastic particles smaller than five millimeters (5 mm) in size. Coastal and bay areas are constantly under continuous and increasing pressure from the activities of humans. Microplastic pollution is now recognized as a great threat to these areas. This study was designed to understand the microplastic pollution of the beaches in Xiamen Bay. The results showed that microplastic abundance was from (28.1±9.4) to (312.7±35.2) n·kg-1. Four main types of microplastics were identified in Xiamen Bay, including fragments, foams, thin films, and fibers. Of the particles analyzed, over 80% were predominantly microplastic fragments and foam, while the films and fiber microplastics accounted for less than 20% of the particles. Studies on the particle size of microplastics also indicated that the microplastics with particle size less than 1 mm accounted for over 60% of the total microparticles, and the abundance of microplastics trend to decrease with increase in the particle size. Fourier transform infrared spectroscopy analysis demonstrated that the major component of the fragments and fibers was identified as polyethylene, and that of foams and films was identified as polystyrene. The scanning electron microscope studies showed that the microplastics presented obvious signs of cracks. In general, Xiamen Bay beach microplastic pollution is at a lower middle level, and land source pollution is the main source of the microplastic pollution.

Single input state polarization-sensitive optical coherence tomography with high resolution and polarization distortion correction.

In single input state polarization-sensitive optical coherence tomography (PS-OCT) with high resolution, the imperfections of quarter-wave plate (QWP) and the sensitivity roll-off mismatch between the two detection channels cause unpredictable polarization distortion. We present a correction method based on the Jones matrix modeling of the system. In a single input PS-OCT system working at 840 nm with an axial resolution of ~2.3 µm, the method yielded better estimation of retardation and optic axis orientation with significantly reduced noise level, especially in weakly birefringent samples. Numerical simulations and quantitative imaging of a sample of known birefringence were performed to validate the performance. We further demonstrate the advantages of our approach with birefringence imaging of swine retina, rat aortic wall, and rat esophageal mucosa for potential clinical applications.

Multiple aperture synthetic optical coherence tomography for biological tissue imaging.

An inherent compromise must be made between transverse resolution and depth of focus (DOF) in spectral domain optical coherence tomography (SD-OCT). Thus far, OCT has not been capable of providing a sufficient DOF to stably acquire cellular-resolution images. We previously reported a novel technique named multiple aperture synthesis (MAS) to extend the DOF in high-resolution OCT [Optica4, 701 (2017)]. In this technique, the illumination beam is scanned across the objective lens pupil plane by being steered at the pinhole using a custom-made microcylindrical lens. Images captured via multiple distinctive apertures were digitally refocused, which is similar to synthetic aperture radar. In this study, we applied this technique for the first time to image both a homemade microparticle sample and biological tissue. The results demonstrated the feasibility and efficacy of high-resolution biological tissue imaging with a dramatic DOF extension.

On the Mechanism of the Improved Operation Voltage of Rhombohedral Nickel Hexacyanoferrate as Cathodes for Sodium-Ion Batteries.

We reported a rhombohedral Na-rich nickel hexacyanoferrate (r-NiHCF) with high discharge voltage, which also possesses long cycle stability and excellent rate capability when serving as the cathode material of Na-ion batteries. First-principles calculations suggest that the high working voltage of r-NiHCF is correlated to the asymmetric residence of Na+ ions in the rhombohedral framework in parallel with the low charge density at the Fe2+ ions. In both aqueous and ether-based electrolytes, r-NiHCF exhibits higher voltage than that of cubic NiHCF. Rate and cycle experiments indicate that r-NiHCF delivers a specific capacity of 66.8 mAh g-1 at the current density of 80 mA g-1, which is approximate to the theoretical capacity of r-NiHCF. A capacity retention of 96% can be achieved after 200 cycles. The excellent stability of r-NiHCF can be assigned to the absence of rhombohedral-cubic phase transition and negligible volume variation during electrochemical redox, as proven by the ex situ XRD patterns at different depths of charge/discharge and the DFT calculations, respectively.

Asymmetric band-pass plasmonic nanodisk filter with mode inhibition and spectrally splitting capabilities.

A compact wavelength band-pass filter based on metal-insulator-metal (MIM) nanodisk cavity is proposed and numerically investigated by using Finite-Difference Time-Domain (FDTD) simulations. It is found that the transmission characteristics of the filter can be easily adjusted by changing the geometrical parameters of the radius of the nanodisk and coupling distance between the nanodisk and waveguide. By extending the length of input/output waveguides, the filter shows the resonant mode inhibition function. Basing on this characteristic, a two-port wavelength demultiplexer is designed, which can separate resonant modes inside the nanodisk with high transmission up to 70%. The waveguide filter may become a potential application for the design of devices in highly integrated optical circuits.

Functional expression of cystic fibrosis transmembrane conductance regulator in mouse chondrocytes.

1. Cystic fibrosis transmembrane conductance regulator (CFTR) is well known for its role in the cystic fibrosis (CF). Recent studies have shown that CF patients and CFTR-deficient mice exhibit a severe abnormal skeletal phenotype, indicating that CFTR may play a role in bone development and pathophysiological processes. However, it is not known whether CFTR has a direct or indirect effect on bone formation. The aim of the present study was to detect the expression and function of CFTR in mouse chondrocytes. 2. Reverse transcription-polymerase chain reaction, western blotting and immunofluorescence were used to characterize the expression of CFTR in primary isolated mouse chondrocytes. Expression of CFTR mRNA and protein was detectable in mouse chondrocytes. Importantly, whole-cell patch-clamp analysis demonstrated that CFTR in mouse chondrocytes is functional as a cAMP-dependent Cl(-) channel that is inhibited by CFTRinh-172. 3. Thus, the results of the present study demonstrate that functional CFTR is expressed in mouse chondrocytes, which offers essential evidence for the potential direct role of CFTR in physiological and pathological processes of bone.