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Songcheng Yin,1,* Zhan Li,2,* Jinyu Huang,1 Zhifeng Miao,1 Junyan Zhang,1 Chunyang Lu,1 Hao Xu,1 Huimian Xu1 1Department of Surgical Oncology, 2Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: The prognostic significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer has long been assessed, yet results remain controversial. Therefore, we performed a meta-analysis to assess the prognostic value and clinicopathological significance of PCNA in gastric cancer. Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases was conducted. Summary odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the correlations between PCNA expression and clinicopathological features, overall survival (OS), and disease-free survival (DFS). Results: A total of 19 studies involving 2,852 participants were included in our analysis. The pooled HR indicated that high PCNA expression was significantly associated with poor OS (HR 1.66, 95% CI 1.32–2.08) and DFS (HR 1.81, 95% CI 1.40–2.36). Subgroup analysis revealed that the association between PCNA and OS was also significant in Asian and European patients. In addition, the pooled ORs showed that high PCNA expression was significantly associated with deeper tumor invasion (OR 2.37, 95% CI 1.71–3.27), lymph node metastasis (OR 2.49, 95% CI 1.85–3.35), and advanced stage cancer (OR 1.89, 95% CI 1.36–2.63). Conclusion: Our meta-analysis indicates that high PCNA expression might be a prognosticator of poor survival and a promising therapeutic target for gastric cancer patients. Keywords: proliferating cell nuclear antigen, gastric cancer, prognosis, biomarker, meta-analysis

PurposeGreat uncertainty exists about the costs associated with whole-genome sequencing (WGS).MethodsOne hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months.ResultsThe incremental cost per patient of WGS testing was $5,098 in cardiology settings and $5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -$1,560, 95% confidence interval -$7,558 to $3,866, p = 0.36; primary care: difference = $681, 95% confidence interval -$884 to $2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than $69 and $182 per patient in cardiology and primary care, respectively.ConclusionShort-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure.Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.35.

© Published by the BMJ Publishing Group Limited. Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments.

Chien-Yu Lu,1,2 Yung-Sung Yeh,3–5 Ching-Wen Huang,5,6, Cheng-Jen Ma,4,5 Fang-Jung Yu,1,2 Jaw-Yuan Wang4–10 1Division of Gastroenterology, Department of Internal Medicine, 2Department of Internal Medicine, Faculty of Medicine, College of Medicine, 3Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 4Graduate Institute of Clinical Medicine, College of Medicine, 5Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 6Graduate Institute of Medicine, College of Medicine, 7Cancer Center, Kaohsiung Medical University Hospital, 8Department of Genomic Medicine, 9Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI) combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT)1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being classified as stable disease and partial response, respectively. Moreover, the progression-free survival was over 6 months. FOLFIRI, with dose escalation of irinotecan according to UGT1A1 genotyping plus regorafenib appears to be a promising salvage therapy for patients with refractory metastatic colorectal cancer. Keywords: UGT1A1, irinotecan, dose escalation, metastatic colon cancer, regorafenib

Jing-Gao Li,1,* Miao-Rong She,2,* Ci-Yong Lu,3 Shan-Shan Wei,2 Ping-Fang Xia,2 Ze-Sheng Lu,2 Qi Peng2 1Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 2Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 3School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms.Materials and methods: The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting.Results: Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression.Conclusion: Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer.Keyword: Bcl-2, farnesyltransferase inhibitor, caspase-9, caspase-3, Bax

We report a rare case of adrenocortical carcinoma spontaneously rupturing. To our knowledge, this is the sixth reported case in literature that is not related to any preceding traumatic incidents or predisposing disease. Upon reviewing previous cases, tumor size greater than 10 cm in adults is a predisposing factor for spontaneous rupture, while the degree of lymph node invasion or the extent of distant metastasis is not indicative. Further study is warranted to validate our finding, but we suggest that if an adrenal tumor suspicious of malignant presentation is found incidentally, the size of tumor may warrant a more aggressive approach for prevention of tumor rupture and decrease in patient morbidity and mortality.

This study aimed to investigate the effect of chronic kidney dysfunction (CKD) on the clinical characteristics of patients with acute coronary syndrome (ACS) and the degree of coronary arterial stenosis. The study enrolled 368 patients with ACS who underwent coronary angiography. Blood glucose, glycated haemoglobin (HbA1c), total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), and serum creatinine were examined randomly, and the severity of coronary artery lesions was assessed using the Gensini score. Patients were divided into three groups according to estimated glomerular filtration rate: normal renal function (n = 102), mild renal insufficiency (n = 198), and moderate to severe renal dysfunction (n = 68). The characteristics of patients with coronary artery lesions in the three groups were analysed. Of all patients, 27.7% had normal renal function. In the moderate to severe renal dysfunction group, the majority of patients were women whose average age was older. The ratio of patients with history of hypertension and diabetes mellitus was higher, random blood glucose, HbA1c, TG, UA and Gensini score were obviously increased, while HDL-C was significantly decreased; all differences had statistical significance (p < 0.05). Different degrees of CKD occur in patients with ACS. In patients with ACS and CKD, metabolism of glucose and fat are significantly abnormal, and coronary arterial lesions are more serious.

Gossip is a common phenomenon in the workplace and yet relatively little is understood about its\ud influence to employees. This study adopts social information theory and social cognitive theory to interpret\ud the diverse literature on gossip, and to develop and test hypotheses concerning some of the antecedents of\ud gossip, with an aim of developing knowledge of the relationship between gossip and employee behaviour in\ud the workplace. The study analysed survey data in a two stage process, from 362 employees across a range\ud of industries in Taiwan. The findings revealed that job-related gossip predicted employee cynicism and\ud mediated the relationship between psychological contract violation and cynicism, and that non-job-related\ud gossip showed a similar but weaker effect to employee cynicism. The contribution made by this paper is of\ud value to both the academic subject domain and managers in Human Resources. Firstly, we have identified\ud two constructs of gossip, job related and non-job related gossip not previously reported and a validated scale\ud has been created. Secondly, we have confirmed that these different constructs of gossip impact differently on\ud employee behaviour and therefore HR managers should be cautious about gossip in the workplace, as it can\ud cause cynical behaviour amongst employees.

A previous study has examined the performance of a fluidized activated carbon adsorber for removal of organics and particulate emissions from an incinerator under various fluidized operating conditions. The results show that it is an effective control device to treat the organics and coarse particles. However toxic heavy metal compounds cannot be completely destroyed during the incineration process and will volatilize at high temperature and then condense to form metallic particulates during the cooling of the flue gas. Therefore, continuing the previous study, the removal of metals generated from incineration by a fluidized bed adsorber at relatively low temperature was performed in the current study. Activated carbons with different additives (limestone, aluminum oxide and silica sand) were added in the adsorber to remove single metal (Pb, Cr and Cd) or mixed metals in the flue gas. Furthermore, an impulse bag house integrated after the adsorber and serving as an air pollution control device to control the metals and organics simultaneously was also identified. The results indicate that different additives can increase the removal efficiency of metals from 4% to 24% when the feedstock contains single metal. The integration of the fluidized bed adsorber and a bag house was effective to remove the heavy metals, organics and particulates in the flue gas.

The Grey model is characterized by basic mathematics and a need for few raw data, but it also lacks the flexibility to adjust the model to increase the precision for the forecasting model. This article shows two types of grey forecasting models, GM(1,1) and NGBM. The GM(1,1) shows its fitting ability to the linear raw data and NGBM is superior in fitting nonlinear raw data. In this article, two practical cases are shown to demonstrate the calculation procedures of both models. The results show they are feasible in forecasting.

The effects of acute intragastric administration of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction were studied in spontaneously breathing dogs. The dogs were given 0.5 g/kg of 10% ethanol (v/v) in 5 min. Hemodynamic measurements were obtained before and 30 min after ingestion of ethanol. Mean pulmonary arterial pressure and pulmonary vascular resistance increased markedly after ingestion of ethanol, and hypoxic pulmonary vasoconstriction was augmented significantly by ethanol as well. Diethylcarbamazine citrate (DEC), a lipoxygenase inhibitor, inhibited these effects of ethanol in a dosage of 200 mg/kg. The above findings suggest that ethanol can induce pulmonary vasoconstriction, which may be predominantly mediated by leukotrienes (LTs).