A Predictive Scoring System Based on Inflammatory and Tumor Markers for Gastric Cancer Patients Undergoing Curative Resection.

PURPOSE: Inflammation is closely associated with prognosis in gastric cancer (GC). We aimed to assess the predictive value of existing inflammatory and tumor markers in GC, to establish a systemic score based on valuable predictors for early risk stratification of patients, and to create a nomogram for individual risk prediction. PATIENTS AND METHODS: We retrospectively analyzed 401 GC patients who underwent curative gastrectomy from 2007 to 2016. RESULTS: Through univariate and multivariate survival analysis, age (>60 years), depth of invasion (pT3-4), lymph node invasion (pN1-3), histologic classification (poor), adjuvant chemotherapy (no), albumin fibrinogen ratio (AFR) (<13.33), and carbohydrate antigen 19-9 (CA19-9) (>27 U/mL) independently indicated inferior disease-free survival (DFS). In addition, depth of invasion, lymph node invasion, histologic classification, adjuvant chemotherapy, AFR, and CA19-9 were incorporated in the prediction of cancer-specific survival (CSS). A combined AFR and CA19-9 prognostic score (CACPS) was established. Lower AFR (<13.33) and higher CA19-9 (>27 U/mL) were allocated 1 point each in the CACPS (range, 0-2). CACPS can be used as an independent predictor for DFS and CSS in multivariate analysis (for DFS: CACPS 1: HR=2.039, 95% CI: 1.357-3.065, P=0.001; CACPS 2: HR=2.419, 95% CI: 1.397-4.186, P=0.002; for CSS: CACPS 1: HR=2.035, 95% CI: 1.292-3.205, P=0.002; CACPS 2: HR=2.255, 95% CI: 1.252-4.059, P=0.007), with a higher CACPS indicating poor survival according to Kaplan-Meier curves (both P<0.001). Moreover, a nomogram for DFS and CSS was generated using the significant characteristics in the multivariate analysis, which exhibited high accuracy (for DFS: C-index=0.743, 95% CI: 0.698-0.788; for CSS: C-index=0.766, 95% CI: 0.718-0.814) versus tumor-node-metastasis staging (for DFS: C-index=0.692, 95% CI: 0.650-0.734; for CSS: C-index=0.720, 95% CI: 0.675-0.764). CONCLUSION: Preoperative CACPS exhibited high accuracy in predicting prognosis for GC patients who underwent curative resection.

Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal angiomyolipoma from renal cell carcinoma: a meta-analysis.

OBJECTIVES: To determine the performance of chemical shift signal intensity index (CS-SII) values for distinguishing minimal-fat renal angiomyolipoma (mfAML) from renal cell carcinoma (RCC) and to assess RCC subtype characterisation. METHODS: We identified eligible studies on CS magnetic resonance imaging (CS-MRI) of focal renal lesions via PubMed, Embase, and the Cochrane Library. CS-SII values were extracted by lesion type and evaluated using linear mixed model-based meta-regression. RCC subtypes were analysed. Two-sided p value <0.05 indicated statistical significance. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Eleven articles involving 850 patients were included. Minimal-fat AML had significantly higher CS-SII value than RCC (p < 0.05); there were no significant differences between mfAML and clear cell RCC (cc-RCC) (p = 0.112). Clear cell RCC had a significantly higher CS-SII value than papillary RCC (p-RCC) (p < 0.001) and chromophobe RCC (ch-RCC) (p = 0.045). The methodological quality was relatively high, and Begg's test data points indicated no obvious publication bias. CONCLUSIONS: The CS-SII value for differentiating mfAML from cc-RCC remains unproven, but is a promising method for differentiating cc-RCC from p-RCC and ch-RCC. KEY POINTS: • RCC CS-SII values are significantly lower than those of mfAML overall. • CS-SII values cannot aid differentiation between mfAML and cc-RCC. • CS-SII values might help characterise RCC subtypes.

Protective effect of antioxidants on the pre-maturation aging of mouse oocytes.

Pre-maturation aging of immature oocytes may adversely affect the fate of an oocyte. Oxidative stress is one of the most detrimental factors affecting oocyte developmental competence and maturation during aging. In this study, experiments were designed to examine whether supplementation of antioxidants in a culture medium could protect immature mouse oocytes from damages caused by oxidative stress. Mouse oocytes at germinal vesicle stage were prevented from meiosis resumption and cultured in a medium with or without antioxidants for 12-36 h to allow oocytes to undergo aging. After aging, oocytes were cultured for maturation. Nuclear maturation, mitochondria activity, spindle morphology and DNA integrity were examined after maturation. It was found that antioxidants had protective effects on the oocytes in terms of nuclear maturation, functional mitochondria, spindle morphology and DNA integrity. As aging time was prolonged from 12 to 36 h, the protective effect of antioxidants became more obvious. However, as compared with oocytes without aging, it was found that aging significantly inhibited nuclear maturation, impaired mitochondria function, and damaged the spindle and DNA. These results indicate that pre-maturation aging is detrimental to oocytes' competence to undergo maturation and other cellular activities, and antioxidants can protect oocytes from damages caused by aging.

Rad9a is required for spermatogonia differentiation in mice.

Spermatogenesis in testes requires precise spermatogonia differentiation. Spermatocytes lacking the Rad9a gene are arrested in pachytene prophase, implying a possible role for RAD9A in spermatogonia differentiation. However, numerous RAD9A-positive pachytene spermatocytes are still observed in mouse testes following Rad9a excision using the Stra8-Cre system, and it is unclear whether Rad9a deletion in spermatogonia interrupts differentiation. Here, we generated a mouse model in which Rad9a was specifically deleted in spermatogonial stem cells (SSCs) using Cre recombinase expression driven by the germ cell-specific Vasa promoter. Adult Rad9a-null male mice were infertile as a result of completely blocked spermatogonia differentiation. No early spermatocytes were detected in mutant testicular cords of 9-day-old mice. Mutant spermatogonia were prone to apoptosis, although proliferation rates were unaffected. Rad9a deletion also resulted in malformation of seminiferous tubules, in which cells assembled irregularly into clusters, and malformation led to testicular cord disruption. Our findings suggest that Rad9a is indispensable for spermatogonia differentiation and testicular development in mice.

Casein kinase 1 (α, δ and ε) localize at the spindle poles, but may not be essential for mammalian oocyte meiotic progression.

CK1 (casein kinase 1) is a family of serine/threonine protein kinase that is ubiquitously expressed in eukaryotic organism. CK1 members are involved in the regulation of many cellular processes. Particularly, CK1 was reported to phosphorylate Rec8 subunits of cohesin complex and regulate chromosome segregation in meiosis in budding yeast and fission yeast. (1-3) Here we investigated the expression, subcellular localization and potential functions of CK1α, CK1δ and CK1ε during mouse oocyte meiotic maturation. We found that CK1α, CK1δ and CK1ε all concentrated at the spindle poles and co-localized with γ-tubulin in oocytes at both metaphase I (MI) and metaphase II (MII) stages. However, depletion of CK1 by RNAi or overexpression of wild type or kinase-dead CK1 showed no effects on either spindle organization or chromosome segregation during oocyte meiotic maturation. Thus, CK1 is not the kinase that phosphorylates Rec8 cohesin in mammalian oocytes, and CK1 may not be essential for spindle organization and meiotic progression although they localize at spindle poles.

Arrested human embryos are more likely to have abnormal chromosomes than developing embryos from women of advanced maternal age.

BACKGROUND: Aneuploidy is one of the major factors that result in low efficiency in human infertility treatment by in vitro fertilization (IVF). The development of DNA microarray technology allows for aneuploidy screening by analyzing all 23 pairs of chromosomes in human embryos. All chromosome screening for aneuploidy is more accurate than partial chromosome screening, as errors can occur in any chromosome. Currently, chromosome screening for aneuploidy is performed in developing embryos, mainly blastocysts. It has not been performed in arrested embryos and/or compared between developing embryos and arrested embryos from the same IVF cycle. METHODS: The present study was designed to examine all chromosomes in blastocysts and arrested embryos from the same cycle in patients of advanced maternal ages. Embryos were produced by routine IVF procedures. A total of 90 embryos (45 blastocysts and 45 arrested embryos) from 17 patients were biopsied and analyzed by the Agilent DNA array platform. RESULTS: It was found that 50% of the embryos developed to blastocyst stage; however, only 15.6% of the embryos (both blastocyst and arrested) were euploid, and most (84.4%) of the embryos had chromosomal abnormalities. Further analysis indicated that 28.9% of blastocysts were euploid and 71.1% were aneuploid. By contrast, only one (2.2%) arrested embryo was euploid while others (97.8%) were aneuploid. The prevalence of multiple chromosomal abnormalities in the aneuploid embryos was also higher in the arrested embryos than in the blastocysts. CONCLUSIONS: These results indicate that high proportions of human embryos from patients of advanced maternal age are aneuploid, and the arrested embryos are more likely to have abnormal chromosomes than developing embryos.