The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis.

OBJECTIVES: Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question. DESIGN: An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed. DATA SOURCES: Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases. ELIGIBILITY CRITERIA: The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI. DATA EXTRACTION AND SYNTHESIS: Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters. RESULTS: The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01). CONCLUSION: Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.

Quantitative Model Establishment for Volatile Oils from Rhizoma Wenyujin Concisum by Near-infrared Spectrometry / 中国药师

Objective: To established a near-infrared spectroscopy quantitative model for the rapid determination of volatile oils from Rhizoma wenyujin concisum. Methods:Firstly, the volatile oils from Rhizoma wenyujin was determined by the distillation method described in Chinese Pharmacopoeia. The quantitative calibration model was established and optimized by fourier transformation near-infrared spectroscopy ( FT-NIR) combined with partial least square ( PLS) regression. The calibration model was evaluated by the coef-ficient (r), root-mean-square error of calibration (RMSEC) and root mean square of cross-validation (RMSECV) of the calibration model as well as the root mean square of prediction ( RMSEP) of prediction model. Results: In the combination of FT-NIR and PLS regression, the spectrum of 7189-4227 cm-1 , 8813-7478 cm-1 and"second spectrum+MSC" were chosen to establishe and optimize the quantitative calibration model. For the quantitative calibration model, the r, RMSEC and RMSECV of volatile oils was 0. 9769, 0. 0907 and 0. 3773, respectively. For the prediction model, the r and RMSEP of volatile oils was 0. 9053 and 0. 1960, respective-ly. Conclusion:The established near-infrared spectroscopy quantitative model is relatively stable, accurate and reliable in the simulta-neous quantitative analysis of volatile oils, and is expected to be used for the rapid determination of volatile oils from Rhizoma wenyujin concisum.

Quantitative Model Establishment for Volatile Oils from Rhizoma Wenyujin Concisum by Near-infrared Spectrometry / 中国药师

Objective: To established a near-infrared spectroscopy quantitative model for the rapid determination of volatile oils from Rhizoma wenyujin concisum. Methods:Firstly, the volatile oils from Rhizoma wenyujin was determined by the distillation method described in Chinese Pharmacopoeia. The quantitative calibration model was established and optimized by fourier transformation near-infrared spectroscopy ( FT-NIR) combined with partial least square ( PLS) regression. The calibration model was evaluated by the coef-ficient (r), root-mean-square error of calibration (RMSEC) and root mean square of cross-validation (RMSECV) of the calibration model as well as the root mean square of prediction ( RMSEP) of prediction model. Results: In the combination of FT-NIR and PLS regression, the spectrum of 7189-4227 cm-1 , 8813-7478 cm-1 and"second spectrum+MSC" were chosen to establishe and optimize the quantitative calibration model. For the quantitative calibration model, the r, RMSEC and RMSECV of volatile oils was 0. 9769, 0. 0907 and 0. 3773, respectively. For the prediction model, the r and RMSEP of volatile oils was 0. 9053 and 0. 1960, respective-ly. Conclusion:The established near-infrared spectroscopy quantitative model is relatively stable, accurate and reliable in the simulta-neous quantitative analysis of volatile oils, and is expected to be used for the rapid determination of volatile oils from Rhizoma wenyujin concisum.

Genomic landscape of CD34+ hematopoietic cells in myelodysplastic syndrome and gene mutation profiles as prognostic markers.

Myelodysplastic syndrome (MDS) includes a group of diseases characterized by dysplasia of bone marrow myeloid lineages with ineffective hematopoiesis and frequent evolution to acute myeloid leukemia (AML). Whole-genome sequencing was performed in CD34(+) hematopoietic stem/progenitor cells (HSPCs) from eight cases of refractory anemia with excess blasts (RAEB), the high-risk subtype of MDS. The nucleotide substitution patterns were found similar to those reported in AML, and mutations of 96 protein-coding genes were identified. Clonal architecture analysis revealed the presence of subclones in six of eight cases, whereas mutation detection of CD34(+) versus CD34(-) cells revealed heterogeneity of HSPC expansion status. With 39 marker genes belonging to eight functional categories, mutations were analyzed in 196 MDS cases including mostly RAEB (n = 89) and refractory cytopenia with multilineage dysplasia (RCMD) (n = 95). At least one gene mutation was detected in 91.0% of RAEB, contrary to that in RCMD (55.8%), suggesting a higher mutational burden in the former group. Gene abnormality patterns differed between MDS and AML, with mutations of activated signaling molecules and NPM1 being rare, whereas those of spliceosome more common, in MDS. Finally, gene mutation profiles also bore prognostic value in terms of overall survival and progression free survival.

Iqcg is essential for sperm flagellum formation in mice.

Mammalian spermatogenesis comprises three successive phases: mitosis phase, meiosis phase, and spermiogenesis. During spermiogenesis, round spermatid undergoes dramatic morphogenesis to give rise to mature spermatozoon, including the condensation and elongation of nucleus, development of acrosome, formation of flagellum, and removal of excessive cytoplasm. Although these transformations are well defined at the morphological level, the mechanisms underlying these intricate processes are largely unknown. Here, we report that Iqcg, which was previously characterized to be involved in a chromosome translocation of human leukemia, is highly expressed in the spermatogenesis of mice and localized to the manchette in developing spermatids. Iqcg knockout causes male infertility, due to severe defects of spermiogenesis and resultant total immobility of spermatozoa. The axoneme in the Iqcg knockout sperm flagellum is disorganized and hardly any typical ("9+2") pattern of microtubule arrangement could be found in Iqcg knockout spermatids. Iqcg interacts with calmodulin in a calcium dependent manner in the testis, suggesting that Iqcg may play a role through calcium signaling. Furthermore, cilia structures in the trachea and oviduct, as well as histological appearances of other major tissues, remain unchanged in the Iqcg knockout mice, suggesting that Iqcg is specifically required for spermiogenesis in mammals. These results might also provide new insights into the genetic causes of human infertility.

Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish.

We previously reported a fusion protein NUP98-IQCG in an acute leukaemia, which functions as an aberrant regulator of transcriptional expression, yet the structure and function of IQCG have not been characterized. Here we use zebrafish to investigate the role of iqcg in haematopoietic development, and find that the numbers of haematopoietic stem cells and multilineage-differentiated cells are reduced in iqcg-deficient embryos. Mechanistically, IQCG binds to calmodulin (CaM) and acts as a molecule upstream of CaM-dependent kinase IV (CaMKIV). Crystal structures of complexes between CaM and IQ domain of IQCG reveal dual CaM-binding footprints in this motif, and provide a structural basis for a higher CaM-IQCG affinity when deprived of calcium. The results collectively allow us to understand IQCG-mediated calcium signalling in haematopoiesis, and propose a model in which IQCG stores CaM at low cytoplasmic calcium concentrations, and releases CaM to activate CaMKIV when calcium level rises.

Generation of an azimuthally polarized beam with a metallic ring core fiber.

A fiber with a thin-metallic layer introduced between the central core and the cladding is proposed to lift the near-degeneracy of the modes TE01, TM01, and HE21. It can be used to obtain the pure mode TE01 as both the active and passive fibers. In the case of the active fiber, the fiber with the appropriate rare earth doping profile in the central core is presented as the gain medium of a fiber laser. The numerical results show that the pure mode TE01 (99.99%) can be obtained. In the case of the passive fiber, Gaussian light beams with suitable shift distance from the center core are coupled into the fiber. The results indicate that only the mode TE01 remains with the increasing propagation distance.

Cognitive impairment and depression among Chinese nonagenarians/centenarians.

PURPOSE: In this study, we explored the association between cognitive impairment and depression in the very elderly using a sample aged 90-108 years. METHODS: A cross-sectional study. RESULTS: The sample included 682 unrelated Chinese nonagenarians/centenarians (67.25% women, mean age of 93.49 years). The mean depression score (measured with the brief 23-item Geriatrics Depression Scale-Chinese Edition was 8.45 (standard deviation [SD] = 3.30). The mean of cognitive function scores (measured with the 30-item Mini-Mental State Examination) was 15.54 (SD = 5.38). There was no significant difference in cognitive function scores between subjects with and without depression, and there was also no significant difference in depression scores between subjects with and without cognitive impairment. There was also no significant difference in the frequency of depression between subjects with and without cognitive impairment or in the frequency of cognitive impairment between subjects with and without depression. Both the odds ratio (OR) of depression (as a function of increased cognitive impairment) and the OR of cognitive impairment (as a function of increased depression) were found to be insignificant. Pearson Correlation also showed no significant correlation between depression scores and cognitive function scores. CONCLUSIONS: In summary, we found that depression was not directly correlated with cognitive impairment in Chinese nonagenarians and centenarians.