Ionizing Radiation-Induced RPL23a Reduction Regulates Apoptosis / 生物医学与环境科学（英文）

Objective@#The expression patterns of ribosomal large subunit protein 23a (RPL23a) in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23a expression and spermatogonia apoptosis upon exposure to X-ray.@*Methods@#Male mice and GC-1 cells were irradiated with X-ray, terminal dUTP nick end-labelling (TUNEL) was performed to detect apoptotic spermatogonia @*Results@#Ionizing radiation (IR) increased spermatogonia apoptosis, the expression of RPL11, MDM2 and p53, and decreased RPL23a expression in mice spermatogonia @*Conclusion@#These results suggested that IR reduced RPL23a expression, leading to weakened the RPL23a-RPL11 interactions, which may have activated p53, resulting in spermatogonia apoptosis. These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility. The graphical abstract was available in the web of www.besjournal.com.

A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia / 中国天然药物

Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.

Rapid screening for Klinefelter syndrome with a simple high-resolution melting assay: a multicenter study / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.

Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer / 癌症

<p><b>INTRODUCTION</b>Preoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer.</p><p><b>METHODS</b>A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable.</p><p><b>RESULTS</b>Of the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of ≤ 5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195-3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484-4.512, P = 0.001) were significantly associated with an increased rate of pCR.</p><p><b>CONCLUSIONS</b>The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.</p>

Outcome analysis of simultaneous liver resection for synchronous liver metastases from colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the outcomes of simultaneous liver resection for patients who have primary colorectal cancer with synchronous hepatic metastases to see if there is any advantage for doing so.</p><p><b>METHODS</b>We retrospectively analyzed the medical records (1999 - 2009) of 53 consecutive patients with synchronously recognized primary colorectal carcinoma and hepatic metastases who underwent simultaneous (40 patients) or two-stage (13 patients) colonic and hepatic resections performed at our hospital.</p><p><b>RESULTS</b>There was no thirty-day mortality in both groups. The two groups had significant differences in mean operation duration [(212.9 ± 72.3) min vs. (326.5 ± 140.2) min, P = 0.014], mean blood loss [(337.5 ± 298.0) ml vs. (594.6 ± 430.5) ml, P = 0.020], post-operative hospital stay [(16.2 ± 8.1) day vs. (25.8 ± 8.5) day, P = 0.001]. The incidence rates of post-operative complications were 25.0% (10/40) and 53.8% (7/13), respectively, in the two groups (P = 0.053). The 1-, 3-, 5-year survival rates in the simultaneous resection group were 95.0%, 57.0% and 37.4%, respectively, with a median overall survival of 40.0 months and median disease-free survival of 14.0 months. The 1-, 3-, 5-year survival rates in the two-stage resection group were 92.3%, 58.7% and 36.7%, respectively, with a median overall survival of 38.0 months and median disease-free survival of 13.0 months. There were no significant differences between the two groups in respect of their survivals (P > 0.05).</p><p><b>CONCLUSIONS</b>Simultaneous colectomy and hepatectomy are safe and efficient for colorectal cancer patients who have synchronous colorectal liver metastases, with less complications and blood loss, and shorter hospital stay compared with the two-stage resection.</p>

Clinicopathological features and prognosis of primary appendiceal adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological characteristics and prognostic factors of primary appendiceal adenocarcinoma.</p><p><b>METHODS</b>The clinicopathological data of 42 patients with primary appendiceal adenocarcinoma treated in the Cancer Hospital of Chinese Academy of Medical Sciences between March 1994 and October 2009 were retrospectively analyzed. The survival analysis was conducted using Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models.</p><p><b>RESULTS</b>A total of 42 patients (29 female and 13 males, median age 56 years) with appendiceal adenocarcinoma were included in this study. Of them, 26 (61.9%) were mucinous adenocarcinoma, 12 (28.6%) were intestinal-type adenocarcinoma and 4 (9.5%) were signet cell carcinoma. 18 patients underwent curative resection, 20 patients received cytoreductive surgery, and 4 patients underwent biopsy only. Thirty patients received systemic chemotherapy (5-Fu-based regimens). One patient who died of postoperative pulmonary embolism on day 8 was excluded from the survival analysis. The overall 1-, 3-, and 5-year survival rate was 80.3%, 46.0% and 38.3%, respectively. Univariate analysis revealed that presence of symptoms of acute appendicitis, curative resection, histological grade, histological subtype, preoperative CEA level, systematic chemotherapy, and stage were all significant factors affecting the survival. Multivariate analysis showed that the preoperative CEA level (P = 0.01), histological grade (P = 0.001), and stage (P = 0.001) were independent prognostic factors.</p><p><b>CONCLUSIONS</b>High level of CEA, G2/3 grade, and advanced stage are associated with poor prognosis in patients with primary appendiceal adenocarcinoma.</p>

In vitro study of transfection of mesenchymal stem cells with adenoviral vector overexpressing human uPA / 上海第二医科大学学报

Objective To identify the isolated rat bone marrow derived mesenchymal stem cells(MSCs),and evaluate the efficiency of adenoviral vector expressing human urokinase type plasminogen activator(uPA) in transfection of rat MSCs and its effect on proliferation of MSCs. Methods MSCs were isolated and purified by pasted wall purification,and were identified by immunicytochemistry.The transfection efficiency of uPA was detected by fluorescent microscopy,the expression of uPA in MSCs was detected by Western blotting,and the proliferation of MSCs was evaluated by MTT. Results The harvested MSCs exhibited the typical appearance of MSCs,and it was revealed by immunohistochemistry that the expression of MSCs markers CD29 and CD90 was positive,while that of CD34 and CD45 was negative.A tendency of increase in expression of green fluorescent protein(GFP) was observed with increase of multiplicity of infection(MOI).After transfection with AduPA for 72 h,the transfection efficiency reached(94.0?1.5)% at MOI of 80,and positive GFP cells could still be observed even after 7 d.The transfected uPA had no effect on the proliferation of MSCs. Conclusion MSCs are favourable genetic vectors to express uPA,and can be used for treatment of liver fibrosis.