Prognostic value of perioperative leukocyte count in resectable gastric cancer

AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.

Secular trend analysis of lung cancer incidence in Sihui city,China between 1987 and 2011

Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear.The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.Methods:Joinpoint regression analysis and the age-period-cohort(APC) model were used to analyze the lung cancer incidence trends in Sihui,Guangdong province,China between 1987 and 2011,and explore the possible causes of these trends.Results:A total of 2,397 lung cancer patients were involved in this study.A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period.Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period,a sharp acceleration was observed in males starting in 2005.The full APC model was selected to describe age,period,and birth cohort effects on lung cancer incidence trends in Sihui.The age cohorts in both sexes showed a continuously significant increase in the relative risk(RR)of lung cancer,with a peak in the eldest age group(80-84 years).The RR of lung cancer showed a fluctuating curve in both sexes.The birth cohorts identified an increased trend in both males and females;however,males had a plateau in the youngest cohorts who were born during 1955-1969.Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts.Social aging,smoking,and environmental changes may play important roles in such trends.

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer

BACKGROUND Programmed death ligand 1(PD-L1) immunotherapy remains poorly efficacious in colorectal cancer(CRC). The recepteur d'origine nantais(RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.AIM To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.METHODS Gene expression data from the Gene Expression Omnibus database(GEO;n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine(FAHZUSM;n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot.RESULTS In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121(32%), 43(11%), 91(24%), and 51(13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment(P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells.CONCLUSION RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.

A multicenter hospital-based diagnosis study of automated breast ultrasound system in detecting breast cancer among Chinese women

Objective： The automated breast ultrasound system（ABUS） is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound（HHUS） and mammography（MG）.Methods： Eligible participants underwent HHUS and ABUS testing; women aged 40–69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System（BI-RADS）.Women in the BI-RADS categories 1–2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true-and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4–5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG.Results： A total of 1,973 women were included in the final analysis. Of these, 1,353（68.6%） and 620（31.4%）were classified as BI-RADS categories 1–3 and 4–5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860（P〈0.001）, respectively; they were 89.2% and0.735（P〈0.001） between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4–5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1–2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG.Conclusions： We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.

CLINICOPATHOLOGICAL STUDY ON 3441 CASES OF BENIGN AND MALIGNANT ULCERS——The National Cooperative Group for Pathological Study on the Canceration of Gastric Ulcer

Resected specimens of benign and malignant gastric ulcers from 3441 cases were studied and compared clinically and pathologically. Among them, 421 cases of malignant ulcer were found. The malignant ulcers differed notably from the ulcerated gastric carcinoma and showed many similarities to the benign chronic gastric ulcer (CGU). The most distinct feature of malignant ulcer was lack of cancerous infiltration and muscular residue in the scar tissue of ulcer base. The existence of this type of ulcer clinically and pathomophologically supports the viewpoint that CGU can undergo malignant change. The rate of malignant change of CGU in this study was 3. 48%.

Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells,rather than tumor cells in the breast cancer microenvironment

BACKGROUND CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment.The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.AIM To investigate the expression status of CD155 and the association with exhausted CD4+helper and CD8+cytotoxic tumor infiltrating lymphocytes(TILs)and PD-L1 in the breast cancer microenvironment.METHODS One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study.Immunohistochemistry was used to detect the expression CD155,PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.RESULTS The proportion of patients with CD155 expression was higher in triple negative breast cancer(72.7%)than in Luminal A patients(22.2%,P<0.05).Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+helper TILs(30%)than patients with negative CD155 expression(21%,P<0.05).Patients with positive CD155 expression also had higher cell counts of exhausted CD4+TILs[47 vs 20/high-power fields(HPF)]and unexhausted CD8+TILs(30 vs 17/HPF)than patients with negative expression(P<0.05).CD155 expression was correlated with increased PD-L1 expression in immune cells,0.8%and 0.02%immune cells expressed PD-L1 in patients with positive and negative CD155 expression,respectively(P<0.05).CONCLUSION CD155 was related to an inhibitory immune breast cancer microenvironment.CD155 was associated with a high proportion of exhausted CD4+and unexhausted CD8+TILs and high PD-L1 expression in immune cells.

Hepatitis B virus X protein accelerates the development of hepatoma

The chronic infection of hepatitis B virus(HBV) is closely related to the occurrence and development of hepatocellular carcinoma(HCC). Accumulated evidence has shown that HBV X protein(HBx protein) is a multifunctional regulator with a crucial role in hepatocarcinogenesis. However, information on the mechanism by which HBV induces HCC is lacking. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator, HBx can modulate nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB) and transcription factor AP-2. Moreover, HBx can affect regulatory non-coding RNAs(ncRNAs) including microRNAs and long ncRNAs(lncRNAs), such as miRNA-205 and highly upregulated in liver cancer(HULC), respectively. HBx is also involved in epigenetic modification, including methylation and acetylation. HBx interacts with various signal-transduction pathways, such as protein kinase B/Akt, Wnt/β-catenin, signal transducer and activator of transcription, and NF-κB pathways. Moreover, HBx affects cellular fate by shifting the balance toward cell survival. HBx may lead to the loss of apoptotic functions or directly contributes to oncogenesis by achieving transforming functions, which induce hepatocarcinogenesis. Additionally, HBx can modulate apoptosis and immune response by direct or indirect interaction with host factors. We conclude that HBx hastens the development of hepatoma.

Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model

人的间充质的干细胞(hMSCs ) 装家到肿瘤地点并且禁止肿瘤细胞的生长。很少对内在的分子的机制被知道连接 hMSCs 到肿瘤房间的指向的抑制。在这研究，我们从 hMSCs 用一个动物移植模型，一个合作文化系统和调节媒介在二根人的 hepatoma 房间线(H7402 和 HepG2 ) 上调查了 hMSCs 的效果。当 SCID 老鼠与 H7402 细胞和 Z3 hMSCs 的一个相等的数字被注射时，动物移植研究证明肿瘤形成的潜伏的时间被延长并且肿瘤尺寸更小。当 co 有教养时与 Z3 房间， H7402 细胞增殖减少了，增加的 apoptosis，和 Bcl-2 的表示， c-Myc，原子抗原(PCNA ) 和 survivin 低是的增殖的房间调整了。在有调节媒介的处理源于 Z3 hMSC 文化以后， H4702 房间出现了减少的形成殖民地的能力和减少的增长。Immunoblot 分析证明 beta-catenin， Bcl-2， c-Myc， PCNA 和 survivin 表示是在 H7402 和 HepG2 房间调整的 down。总起来说，我们的调查结果证明 hMSCs 禁止 H7402 和 HepG2 人的肝癌症房间线的恶意的显型，它包括增长，形成殖民地的能力和 oncogene 表示试管内和体内。而且，我们的研究提供表明小径的 Wnt 可以在调停 hMSC 的指向和肿瘤房间抑制有一个角色的证据。

Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County,Guangdong Province,South China:an age-period-cohort analysis

Introduction:In the past several decades,declining incidences of nasopharyngeal carcinoma(NPC) have been observed in Chinese populations in Hong Kong,Taiwan,Los Angeles,and Singapore.A previous study indicated that the incidence of NPC in Sihui County,South China remained stable until 2002,but whether age,diagnosis period,and birth cohort affect the incidence of NPC remains unknown.Methods:Age-standardized rates(ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011.Joinpoint regression analysis was conducted to quantify the changes in incidence trends.A Poisson regression age-period-cohort model was used to assess the effects of age,diagnosis period,and birth cohort on the risk of NPC.Results:The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females.The incidence of NPC remained stable at a non-significant average annual percent change of 0.2%for males and-1.6%for females throughout the entire period.A significantly increased estimated annual percent change of 6.8%(95%confidence interval,0.1%-14.0%) was observed from 2003 to 2009 for males.The relative risk of NPC increased with advancing age up to 50-59 and decreased at ages >60 years.The period effect curves on NPC were nearly flat for males and females.The birth cohort effect curve for males showed an increase from the1922 cohort to the 1957 cohort and a decrease thereafter.In females,there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort.Conclusions:The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011,with an increase from 2003 to 2009.The relative risks of NPC increased in younger females.

Hepatitis B virus X protein enhances hepatocarcinogenesis by depressing the targeting of NUSAP1 mRNA by miR-18b

Objective: The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis.Methods: We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer.Results: In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1(NUSAP1) as one of the target genes of miR-18b.NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b.Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro.Conclusions: Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBxmodulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

Discovery and Characterization of a Thermostable Esterase from an Oil Reservoir Metagenome

With the aim of identifying novel thermostable esterases, comprehensive sequence databases and cloned fosmid libraries of metagenomes derived from an offshore oil reservoir on the Norwegian Continental Shelf were screened for enzyme candidates using both sequence-and function-based screening. From several candidates identified in both approaches, one enzyme discovered by the functional approach was verified as a novel esterase and subjected to a deeper characterization. The enzyme was successfully over-produced in Escherichia coli and was shown to be thermostable up to 90°C, with the highest esterase activity on short-chain ester substrates and with tolerance to solvents and metal ions. The fact that the thermostable enzyme was solely found by functional screening of the oil reservoir metagenomes illustrates the importance of this approach as a complement to purely sequence-based screening, in which the enzyme candidate was not detected. In addition, this example indicates the large potential of deep-sub-surface oil reservoir metagenomes as a source of novel, thermostable enzymes of potential relevance for industrial applications.

Research progress in hepatitis B virus covalently closed circular DNA

Hepatitis B virus(HBV)infections are a global public health issue.HBV covalently closed circular DNA(cccDNA),the template for the transcription of viral RNAs,is a key factor in the HBV replication cycle.Notably,many host factors involved in HBV cccDNA epigenetic modulation promote the development of hepatocellular carcinoma(HCC).The HBV cccDNA minichromosome is a clinical obstacle that cannot be efficiently eliminated.In this review,we provide an update on the advances in research on HBV cccDNA and further discuss factors affecting the modulation of HBV cccDNA.Hepatitis B virus X protein(HBx)contributes to HBV cccDNA transcription and the development of hepatocarcinogenesis through modulating host epigenetic regulatory factors,thus linking the cccDNA to hepatocarcinogenesis.The measurable serological biomarkers of continued transcription of cccDNA,the effects of anti-HBV drugs on cccDNA,and potential therapeutic strategies targeting cccDNA are discussed in detail.Thus,this review describes new insights into HBV cccDNA mechanisms and therapeutic strategies for cleaning cccDNA,which will benefit patients with liver diseases.

Medical expenditures for colorectal cancer diagnosis and treatment: A 10-year high-level-hospital-based multicenter retrospective survey in China, 2002-2011

Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.

Sun-burn induced upper limb lymphedema 11 years following breast cancer surgery: A case report

BACKGROUND Upper arm lymphedema is a common complication one year after breast cancer surgery,which profoundly impacts patients'quality of life.CASE SUMMARY We reported a case of lymphedema induced by prolonged sun exposure 11 years after breast cancer surgery.CONCLUSION Breast screening,patient education and follow-up after hospital discharge could help to prevent upper-arm lymphedema.

Immunoexpression and prognostic role of p53 in different subtypes of epithelial ovarian carcinoma

We sought to investigate the significance of p53 expression for epithelial ovarian carcinoma.In this study,we used immunohistochemical method to investigate the expression patterns of p53 in different subtypes of epithelial ovarian carcinoma.We found that the expressions of p53 protein in epithelial ovarian cancer（pituita,serosity and intima） were 88.9%,75% and 100%,respectively,while the recurrence rates among three cancer subtypes were significantly different（33.3%,12.5% and 0%,respectively;P 〈 0.05）.Compared with patients without lymph node metastasis,the expression of p53 in patients with lymph node metastasis was significantly strong（68.75% and 100%,respectively;P 〈 0.05）.However,the recurrence rate in the patients with lymph node metastasis（40%） was higher than that without lymph node metastasis（6.25%,P 〈 0.05）.The expressions of p53 protein in ovarian cancer betweenⅠ-Ⅱ（25%） stage and Ⅱ-Ⅳ stage（100%） were significantly different（P 〈 0.05）,and the recurrence rates between the two groups were significantly different（0% and 31.25%,respectively,P 〈 0.05）.Therefore,p53 protein has an intimate relationship with the malignant degree and the prognosis of ovarian cancer.

IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF CYTOCHROME P-450HSjISOZYME, AN ENZYME RELATED TO NITROSAMINE METABOLISM, IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA

Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.

IMMUNOLOGICAL DIAGNOSIS OF LIGHT CHAIN DISEASE ANALYSIS OF 11 CASES FOUND IN FUJIAN PROVINCE

The present paper reports 11 cases of light chain disease (LCD) sequently found in several citles over Fujian province, Immunological classification of this group of LCD ww as follows: six of me cases belonged to type λ, four of them were type κ, and another one was a double LCD. We found that LCD was common in Fujlan only next to multiple myeloma (MM) of IgG class and accounted for 20% of the total 55 MM cases found in recent yean.It to well known that In matt patients of LCD M protein or Bence Jones proteinemia (BJPemia) to not detectable by conventional electro-phoresis. Our studies show that by making serum protein along with urinary BJP electrophoresis on the same one gel plate the sltuation can be greatly Improved It not only favour* the recognition of smail and faint band or bands of free light chain in serum, but also provides a repid and sensitive way, i. e. , immunofixation, to directly detect urinary light chain on the gel plate Immediately after electrophresis has been run.

The Culture of Incident Reporting and Feedback: A Cross-Sectional Study in a Hospital Setting

A safety culture where incidents have been reported and feedback given is essential to detect and understand system failures. The aims of this study were to examine the culture of incident reporting and feedback (the incident culture) in a hospital setting, and the associations between the incident culture and other dimensions of the safety culture. A cross-sectional study was carried out with the instrument Hospital Survey on Patient Safety Culture (HSOPSC) within 16 units in six somatic hospitals at a Norwegian Hospital Trust. Units with identical specialities across the hospitals constitute a clinic. HSOPSC measures the health care personnel’s perception of the safety culture, seven safety dimensions at the unit level, three at the hospital level and four outcome measures. The outcome measures “Frequency of event reporting” and the dimension “Feedback and communication about error” were combined into the variable “incident culture”, score 1 - 5. A positive score was defined as ≥ 4.0. This study included 631 health care personnel. The mean score for the incident culture was 3.10 (SD 0.65) with significant differences between the clinics, and the hospitals. The strongest predictors for the incident culture were the dimensions “Communication openness” (linear regression slope B 0.470;95% CI 0.398 to 0.543;p < 0.001), “Manager expectations and actions promoting safety” (B 0.378;95% CI 0.304 to 0.453;p < 0.001), “Organisational learning and continuous improvement” (B 0.374;95% CI 0.293 to 0.455;p < 0.001) and “Teamwork across hospital units” (B 0.360;95% CI 0.261 to 0.459;p < 0.001). In this study, the incident culture needed improvements. To improve the incident culture, the attention may be directed towards developing and maintaining a culture of open communication, management that promotes safety, and a learning organisation and teamwork between the units.

Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China:a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.

Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2

肝炎 B 病毒 X 蛋白质(HBx ) 在 hepatocellular 癌的发展起一个关键作用。这里，我们寻求了识别 HBx 由调停的机制肝房间增长。我们发现那 HBx upregulated cyclooxygenase-2 (COX-2 ) 的层次， 5-lipoxygenase (5 哈鱼) 和 phosphorylated 在肝房间的细胞外的调整信号的蛋白质 kinases 1/2 (p-ERK1/2 ) 。导致 HBx 的 p-ERK1/2 被 Gi/o 蛋白质，艇长或哈鱼的抑制废除。另外， HBx 增加了前列腺素 E2 (PGE2 ) 的数量，免除房间线的 leukotriene B4 (LTB4 ) 源于 hepatocytes。而且，这些释放 arachidonic 酸代谢物能激活 ERK1/2。有趣地，激活 ERK1/2 能 upregulate 以一种积极反馈方式的 COX-2 和 5 哈鱼的表示。在结论， HBx 经由包含 COX-2， 5 哈鱼，释放 arachidonic 酸代谢物， Gi/o 蛋白质和 p-ERK1/2 的一个积极反馈环提高并且维持肝房间增长。