A panel of autoantibodies against tumor-associated antigens in the early immunodiagnosis of lung cancer

ObjectiveLung cancer (LC) is one of the most common malignant tumors worldwide with low five-year survival rate due to lack of effective diagnosis. This study aims to find an optimal combination of autoantibodies for detecting of early-stage LC.MethodsNine relatively novel autoantibodies against tumor-associated (TAAs) (PSIP1, TOP2A, ACTR3, RPS6KA5, HMGB3, MMP12, GREM1, ZWINT and NUSAP1) were detected by using ELISA. Diagnostic models were developed by using the training set (n = 644) and further validated in another independent set (n = 248). We also evaluated the diagnostic accuracy of the model to detect benign lung diseases (BLD) from the early-stage lung cancer.ResultsThe areas under the receiver operating characteristic curve (AUC) for the model with three TAAs panel (GREM1, HMGB3 and PSIP1) was 0.711(95% CI 0.674–0.746) in the training set and 0.858 (95% CI 0.808–0.899) in the validation set, which demonstrated a higher diagnostic capability. The AUC of this three TAAs model was 0.833 (95%CI 0.780–0.878) in discriminating LC from BLD. This model could identify early-stage LC patients from normal control (NC) individuals, with AUC of 0.687(95% CI 0.634–0.736) in training set and AUC of 0.920(95% CI 0.860–0.960) in validation set, and the overall AUC for early-stage LC was 0.779(95% CI 0.739–0.816) when the training set and validation set were combined.ConclusionsThe model with three TAAs panel would detect LC with higher effectiveness, and might be potential screening method for the early LC.     

The epidermal growth factor receptor pathway in relation to pelvic lymph node metastasis and survival in early-stage cervical cancer

The objective of this study is to correlate the expression of epidermal growth factor receptor (EGFR) components with clinical behavior of early-stage cervical cancer. Tissue samples of 336 consecutive Federation of International Gynecologists and Obstetricians stage IB-IIA cervical cancer patients all treated primarily by radical surgery were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. As representatives for the EGFR pathway, expression of EGFR, pEGFR, PTEN, pAKT, and pERK was assessed by immunohistochemistry on tissue microarrays. Positive immunostaining was observed for EGFR in 32.1%, for pEGFR in 21.0%, for PTEN in 38.3%, for pAKT in 5.3%, and for pERK in 4.3% of tumor samples. Positive EGFR immunostaining was associated with squamous cell carcinoma of the cervix (odds ratio [OR], 7.41; 95% confidence interval [CI], 3.38-16.23, P < .001), negative pEGFR immunostaining with poor differentiation (OR, 0.39; 95% CI, 0.20-0.73, P = .004), and negative PTEN immunostaining with metastatic pelvic lymph nodes (OR, 0.51; 95% CI, 0.30-0.90, P = .019). In multivariate analysis, only pelvic lymph node metastasis (hazard ratio, 6.11; 95% CI, 3.46-10.77, P < .001) and poor differentiation (hazard ratio, 1.91; 95% CI, 1.12-3.26, P = .018) were related to disease-specific survival. In early-stage cervical cancer, loss of PTEN expression is associated with pelvic lymph node metastasis, suggesting PTEN to be one of the tumor suppressor genes affecting pelvic lymph node metastasis. However, expression of EGFR pathway components does not appear to have prognostic impact in surgically treated early-stage cervical cancer.     

TNFSF4 polymorphisms are associated with systemic lupus erythematosus in the Malaysian population

Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T‐cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real‐time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs). Allelic and genotypic frequencies of each SNP were calculated for each ethnic group, and association test was performed using logistic regression. The overall association of each SNP in Malaysian patients with SLE was determined with meta‐analysis. The frequency of minor T allele of TNFSF4 rs2205960 was significant in Chinese and Indian patients with SLE, with P values of 0.05 (OR = 1.27, 95% CI: 1.00–1.61) and 0.004 (OR = 3.16, 95% CI: 1.41–7.05), respectively. Significant association of minor G allele of rs704840 with SLE was also observed in Chinese (P = 0.03, OR = 1.26, 95% CI: 1.02–1.56). However, after Bonferroni correction, only T allele of rs2205960 remained significantly associated with Indian cohort. Overall, minor G allele of rs704840 showed significant association with SLE in the Malaysian population with P values of 0.05 (OR = 1.20, 95% CI: 1.00–1.43). We suggested TNFSF4 rs704840 could be the potential SLE risk factors in the Malaysian population.     

2 型糖尿病合并急性脑梗死患者外周血中性粒细胞与淋巴细胞比值的临床意义

目的:探讨外周血中性粒细胞与淋巴细胞比值在2 型糖尿病合并急性脑梗死患者中的临床意义,为临床诊治提供理论依据。方法:选取本院神经内科2014 年1 月~2016 年12 月就诊的2 型糖尿病合并急性脑梗死患者136 例作为研究组,同期体检的68 例糖尿病患者作为对照组,检测患者白细胞计数(WBC)、中性粒细胞计数(NC)、淋巴细胞计数(LC)及中性粒细胞/ 淋巴细胞比值(NLR)。通过受试者工作特征曲线(ROC)和曲线下面积(AUC)评价WBC、NC、LC、NLR 在2 型糖尿病合并急性脑梗死患者诊断中的作用。结果:研究组患者WBC、NC、NLR 的水平明显高于对照组(P<0.05);而LC 水平明显低于对照组(P<0.05)。研究组患者WBC、NC、NLR 的水平随着NIHSS 评分升高而增加(P<0.05);而LC 水平随着NIHSS 评分升高而降低(P<0.05)。NLR、WBC、NC 及LC 诊断糖尿病合并急性脑梗死曲线下面积分别为0.856、0.717、0.685、0.321,灵敏度分别为0.838、0.596、0.517、0.208,特异度分别为0.868、0.838、0.793、0.559。结论:NLR 可以作为诊断2 型糖尿病合并急性脑梗死患者的生物标志物。     

Postoperative carcinoembryonic antigen level has a prognostic value for distant metastasis and survival in rectal cancer patients who receive preoperative chemoradiotherapy and curative surgery: a retrospective multi-institutional analysis

The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3–4 weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5 ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5 ng/mL. After a median follow-up time of 46.7 months, patients with postoperative CEA level >2.5 ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6 %, P < 0.001) and overall survival (OS) (78.1 vs. 88.3 %, P < 0.001) at 5 years than patients with postoperative CEA level ≤2.5 ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95 % CI 1.221–1.996; P < 0.001) and OS (HR 2.073; 95 % CI 1.498–2.869; P < 0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P = 0.004), but not for locoregional recurrence (P = 0.472). Postoperative CEA level >2.5 ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery.     

European Multicentre Survey of in Vitro Antimicrobial Resistance in Helicobacter pylori

A multicentre in vitro survey was carried out in 1998 in 22 European centres in order to assess the variation in the prevalence of Helicobacter pylori resistance. The susceptibility of 1,274 isolates to metronidazole, clarithromycin and amoxicillin was determined by the E test. The mean rate of resistance to metronidazole was 33.1% (95% CI, 7.5–58.9), to clarithromycin 9.9% (95% CI, 0–28.1) and to amoxicillin 0.8% (95% CI, 0–8.9). Resistance to metronidazole was significantly higher in females (P<0.001), while resistance to clarithromycin was significantly higher in children and teens (P<0.05). Resistance to both agents also tended to be higher in strains isolated from patients from southern European countries than in those isolated from patients from central or northern Europe. Overall, these results emphasize the need for further surveys of Helicobacter pylori sensitivity to antibiotics at a national and regional level. Electronic Publication     

EGFR expression and gene copy number in triple-negative breast carcinoma

Most basal-like breast carcinomas are estrogen receptor negative, progesterone receptor negative, and cerb-B2/HER-2/neu negative—the so-called triple-negative breast carcinomas—with high epidermal growth factor receptor (EGFR) expression, which makes EGFR a target of treatment. We evaluated EGFR expression by immunohistochemistry (IHC) with two different clones (EGFR.31G7 and EGFR.25) and gene copy number by fluorescence in situ hybridization (FISH) with Locus specific identifier EGFR/CEP 7 dual probe in 62 triple-negative breast carcinomas. Any complete or incomplete membranous and/or cytoplasmic expression was regarded as IHC positive. Cases showing gene amplification (a ratio of EGFR gene to chromosome 7 of ≥2 or 15 copies per cell in ≥10% of cells) and high polysomy (≥4 copies in ≥40% of cells) were considered FISH positive. We detected EGFR.31G7 positivity in 38 of 62 cases (61.4%), which was composed of 12 of 62 (19.4%) cytoplasmic, 14 of 62 (22.6%) incomplete membranous, and 12 of 62 (19.4%) complete membranous staining. Among 38 of 49 (77.6%) EGFR.25-positive cases, 7 of 49 (14.3%) exhibited cytoplasmic, 10 of 49 (20.4%) exhibited incomplete membranous, and 21 of 49 (42.9%) exhibited complete membranous staining pattern. Ten of 62 (16.1%) FISH-positive cases were identified; 1 of 62 (1.6%) showed amplification, and the rest showed high polysomy. All FISH-positive cases were also found to be IHC positive (P = 0.01) by both EGFR clones. The amplified case displayed strong complete membranous staining with both clones. Among the high polysomic cases; 4 of 9 (44.4%) incomplete membranous, 4 of 9 (44.4%) complete membranous and 1 of 9 (11.1%) cytoplasmic expression of EGFR.31G7, and 6 of 8 (75%) complete membranous and 2 of 6 (25%) cytoplasmic expression of EGFR.25 were detected. Here, we report that membranous EGFR expression is associated with increased gene copy number (P = 0.035 for EGFR.31G7 and P = 0.026 for EGFR.25 clone). Because the markers to predict anti-EGFR treatment response in other system tumors such as EGFR mutation and amplification seem to be rare events in breast cancer, membranous staining pattern of EGFR might be the best way to decide the patient eligibility for anti-EGFR therapy.     

Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China

The study aimed to explore the correlations between status of epidermal growth factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients with lung adenocarcinoma indentified with status of EGFR mutations from August 2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were confirmed with EGFR mutations. The associations among EGFR mutations, clinical factors, and distant metastases at initial diagnosis were evaluated. Patients harboring EGFR mutation were more likely to be female (P < 0.001), with no smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG performance scores (P = 0.025). The correlation between EGFR mutation status and distant metastases showed statistical significance both in univariate (P = 0.022) and in multivariate analysis (OR 1.573, 95 % CI 1.202–2.059, P = 0.001) especially in brain metastases (OR 1.675, 95 % CI 1.132–2.479, P = 0.010) and lung metastases (OR 1.571, 59 % CI 1.101–2.243 P = 0.013). Furthermore, the 19del mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028–2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065–2.346, P = 0.023). The exon 21 point mutations showed statistically significant differences in liver metastases (OR 1.987, 95 % CI 1.094–3.067, P = 0.024). In conclusion, the EGFR mutations in lung adenocarcinoma patients were independently correlated with distant metastases. Subgroup analyses showed that patients harboring 19del mutations presented different distant metastases compared with those harboring 21 point mutaions.     

The level of thymic stromal lymphopoietin and its gene polymorphism are associated with rheumatoid arthritis

ObjectiveTo study the correlation between TSLP gene SNPs and RA in a Han Chinese population.MethodsThe genotypes of TSLP genes rs11466749, rs11466750 and rs10073816 among 197 RA patients and 197 controls were analysed by direct sequencing. ELISA was used to detect the plasma TSLP level. Logistic regression analysis was also conducted to identify risk factors for RA.ResultsThe rs11466749 locus GG genotype (OR = 5.30, 95% CI: 1.76–15.95, P < 0.01), dominant model (OR = 1.68, 95% CI: 1.03–2.73, P = 0.04), recessive model (OR = 5.15, 95% CI: 1.72–15.43, P < 0.01), and G allele (OR = 2.02, 95% CI: 1.33–3.09, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus AA genotype (OR = 4.58, 95% CI: 1.49–14.01, P < 0.01), dominant model (OR = 1.75, 95% CI: 1.09–2.79, P = 0.03), recessive model (OR = 4.27, 95% CI: 1.40–13.00, P = 0.03) and A allele (OR = 1.94, 95% CI: 1.29–2.91, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus GA genotype (OR = 0.29, 95% CI: 0.18–0.45, P < 0.01), dominant model (OR = 0.32, 95% CI: 0.21–0.49, P < 0.01) and A allele (OR = 0.45, 95% CI: 0.32–0.63, P < 0.01) were related to a decreased risk of RA susceptibility. The rs1466749 locus GG genotype, rs11466750 AA genotype, and rs10073816 GG genotype were independent risk factors for RA (P < 0.05). The AUC of plasma TSLP level in the diagnosis of RA was 0.8661 (95% CI: 0.8301–0.9002, P < 0.001). There were statistically significant differences in plasma TSLP levels among subjects with different genotypes at rs11466749, rs11466750, and rs10073816 in the TSLP gene (P < 0.05).ConclusionPlasma TSLP levels are a potential molecular marker of RA. SNPs at rs11466749, rs11466750 and rs10073816 of the TSLP gene are related to the susceptibility of the Han Chinese population to RA.     

HPV and lung cancer risk: A meta-analysis

The potential causal association between human papillomavirus (HPV) and lung cancer (LC) remains controversial. We performed this meta-analysis to evaluate whether HPV infection in lung tissue is associated with LC compared with non-cancer controls. We also quantified this association in different LC subtypes. MEDLINE, EMBASE and Web of Science were searched through March 2014, using the search terms “lung cancer”, “human papillomavirus”, “HPV” and their combinations. Association was tested using odds ratio (OR) with 95% confidence intervals (95% CI). Heterogeneity was assessed using Q and I² statistic. Finally, nine studies, for a total of 1094 LCs and 484 non-cancer controls, were identified as eligible publications. The pooled results showed that HPV infection was associated with LC (OR = 5.67, 95% CI: 3.09–10.40, P < 0.001). Similar results were also observed in HPV16 and/or HPV18 (HPV16/18) infection analyses (OR = 6.02, 95% CI: 3.22–11.28, P < 0.001). HPV16/18 was significantly associated with lung squamous cell carcinoma (SCC) (OR = 9.78, 95% CI: 6.28–15.22, P < 0.001), while the pooled OR was 3.69 in lung adenocarcinoma (95% CI: 0.99–13.71, P = 0.052). Our results suggest that lung tissue with HPV infection has a strong association with LC, and especially, HPV16/18 infection significantly increases SCC risk, which indicates a potential pathogenesis link between HPV and LC.     

Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan,Southeast Iran

In this study we aimed to evaluate the possible association of PTPN22 rs2476601 as well as epidermal growth factor receptor (EGFR) rs17337023 gene polymorphism and rheumatoid arthritis (RA) in a sample of Iranian population. This case‐control study was performed on 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood and PTPN22 rs2476601 and EGFR rs17337023 polymorphisms were determined using tetra amplification refractory mutation system–polymerase chain reaction (T‐ARMS‐PCR). The results showed that PTPN22 rs2476601 CT genotype as well as rs2476601 T allele was a risk factor for susceptibility to RA (OR=5.89 95%CI = 1.78–19.48, P = 0.004 and OR = 4.78, 95%CI = 1.59–14.35, P = 0.003, respectively). We also found that EGFR rs17337023 AT and rs17337023 TT genotypes were risk factor for susceptibility to RA (OR = 9.94 95%CI = 3.65–26.73, P < 0.001 and OR = 3.66, 95%CI = 1.46–9.15, P = 0.005, respectively). In addition the EGFR rs17337023 T allele was a risk for predisposition to RA (OR = 1.56, 95%CI=1.06‐2.30, P = 0.030). In conclusion, we found an association between PTPN22 rs2476601 and EGFR rs17337023 polymorphisms and the risk of RA in a sample of Iranian population.     

Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma

Background

Epidermal growth factor receptor (EGFR) is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC). The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody) on ESCC radiotherapy (RT) and underlying mechanisms.

Methods

Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model.

Results

Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression) in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR) induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (P<0.05), and even after the administration of Nimotuzumab, the RT response of IGFBP-3 silenced KYSE30 cells was not enhanced (P>0.05). In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029), and also with IGFBP-3 up-regulation in tumor tissue.

Conclusions

Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.

     

Immunological diagnosis of tuberculosis based on recombinant antigens ESAT-6 and CFP-10 in children from an endemic area in northeast Brazil

Diagnostic tests for tuberculosis (TB) using interferon gamma (IFN‐γ) responses produced by T lymphocytes after stimulation by early secretory antigen target 6 (ESAT‐6), culture filtrate protein 10 (CFP‐10) or purified protein derivate (PPD) were carried out using ELISA (enzyme‐linked immunosorbent assay) in whole blood culture supernatants from children with suspected TB disease (n = 21), latent TB infection (LTBI; n = 17) and negative controls (NC; n = 21) from Recife, Pernambuco, Brazil. The results were analysed using the ROC (receiver operating characteristic) curves and the areas under the curve (AUC) generated varied from 0.5 to 1.0 with higher values indicating increased discriminatory ability. Comparisons of AUCs were made using non‐parametric assumptions, and the differences were considered significant if P < 0.05. The ROC curve showed a statistical difference (P = 0.015) between the LTBI and NC groups with an AUC of 0.731, TB disease and NC (AUC = 0.780; P = 0.002) and a group with TB (latent infection + disease, n = 38) and NC (AUC = 0.758; P = 0.001) when the antigen used was ESAT‐6. No statistical difference was found between the groups when CFP‐10 or PPD was used. In conclusion, the ESAT‐6 test may be the most appropriate for diagnosis of childhood TB, both LTBI and TB disease, when associated with epidemiological and clinical data, especially in endemic areas such as Brazil.     

Monitoring of cyclooxygenase-2 levels can predict EGFR mutations and the efficacy of EGFR-TKI in patients with lung adenocarcinoma

Background: Epidermal growth factor receptor (EGFR) mutation detection has become a routine molecular test with significant implications for prognosis and therapeutic options of EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, acquiring sufficient amounts of tissue for analyzing EGFR mutations is not often feasible, and not all the patients with sensitive EGFR mutations have benefit from EGFR-TKI treatment. Method: EGFR mutations were detected by amplification refractory mutation system (ARMS) in 44 patients of newly diagnosed lung adenocarcinoma, and patients with EGFR-positive mutations received EGFR-TKI treatment. The serum cyclooxygenase-2 (COX-2) levels were tested before EGFR-TKI treatment and on the 30th days after EGFR-TKI treatment. Results: Twenty-nine cases were detected EGFR mutations. EGFR mutation rate of serum COX-2 high-level group was significantly higher than low-level group (92.9% vs. 53.3%, P = 0.025). Multivariate analysis showed that serum COX-2 level was independently associated with EGFR mutation (P = 0.033, OR = 12.385, 95%CI, 1.231-124.567). Analysis of the correlation between clinical characteristics and the response of EGFR-TKI showed that the serum COX-2 high-level group had a better efficacy than low-level group (P = 0.000), and multivariate logistic regression analysis showed that the serum COX-2 level was the independently influencing factor (P = 0.004). Kaplan-Meier analysis showed that patients of COX-2 high-level group have longer progression-free survival (PFS, P = 0.013), and the Cox regression analysis showed that the same result (P = 0.003; OR = 0.980, 95% CI, 0.967-0.993). Conclusion: The serum COX-2 level seems to be closely associated with EGFR mutations in patients with Lung adenocarcinoma. The serum COX-2 level could help us to predict the responses of EGFR-TKI and the PFS in patients harboring EGFR mutation.     

Quick Sequential Organ Failure Assessment Score and the Modified Early Warning Score for Predicting Clinical Deterioration in General Ward Patients Regardless of Suspected Infection

BackgroundThe quick sequential organ failure assessment (qSOFA) score is suggested to use for screening patients with a high risk of clinical deterioration in the general wards, which could simply be regarded as a general early warning score. However, comparison of unselected admissions to highlight the benefits of introducing qSOFA in hospitals already using Modified Early Warning Score (MEWS) remains unclear. We sought to compare qSOFA with MEWS for predicting clinical deterioration in general ward patients regardless of suspected infection.MethodsThe predictive performance of qSOFA and MEWS for in-hospital cardiac arrest (IHCA) or unexpected intensive care unit (ICU) transfer was compared with the areas under the receiver operating characteristic curve (AUC) analysis using the databases of vital signs collected from consecutive hospitalized adult patients over 12 months in five participating hospitals in Korea.ResultsOf 173,057 hospitalized patients included for analysis, 668 (0.39%) experienced the composite outcome. The discrimination for the composite outcome for MEWS (AUC, 0.777; 95% confidence interval [CI], 0.770–0.781) was higher than that for qSOFA (AUC, 0.684; 95% CI, 0.676–0.686; P < 0.001). In addition, MEWS was better for prediction of IHCA (AUC, 0.792; 95% CI, 0.781–0.795 vs. AUC, 0.640; 95% CI, 0.625–0.645; P < 0.001) and unexpected ICU transfer (AUC, 0.767; 95% CI, 0.760–0.773 vs. AUC, 0.716; 95% CI, 0.707–0.718; P < 0.001) than qSOFA. Using the MEWS at a cutoff of ≥ 5 would correctly reclassify 3.7% of patients from qSOFA score ≥ 2. Most patients met MEWS ≥ 5 criteria 13 hours before the composite outcome compared with 11 hours for qSOFA score ≥ 2.ConclusionMEWS is more accurate that qSOFA score for predicting IHCA or unexpected ICU transfer in patients outside the ICU. Our study suggests that qSOFA should not replace MEWS for identifying patients in the general wards at risk of poor outcome.     

Analysis of Risk Factors for Ventilator-Associated Pneumonia in a Multidisciplinary Intensive Care Unit

 A prospective study was conducted to determine the incidence, risk factors and pathogens of ventilator-associated pneumonia (VAP) in 198 patients requiring mechanical ventilation for more than 48 hours. VAP occurred in 67 (33.8%) patients. Risk factors associated with VAP were admission APACHE II score >20 (odds ratio [OR] 4.77, 95% confidence interval [CI] 2.04–11.27, P<0.001), mechanical ventilation >10 days (OR 44.4, 95% CI 2.16–26.7, P<0.0001), ICU length of stay >10 days (OR 9.4, 95% CI 3.55–25.65, P<0.0001), and admission PaO₂/FiO₂ ratio <200 mmHg (OR 3.4, 95% CI 1.00–11.41, P<0.05). Logistic regression analysis showed a relationship between VAP and length of stay in ICU, duration of fever and presence of catheter-related infection. The pathogens isolated were predominantly gram-negative bacteria (83.2%), with a high proportion of Acinetobacter spp. (35%) resistant to commonly used antimicrobial agents. The mortality rate was not influenced by VAP.     

Association of with‐no‐lysine kinase 1 and Serine/Threonine kinase 39 gene polymorphisms and haplotypes with essential hypertension in Tibetans

Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With‐No‐Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region. Patients were genotyped for nineteen WNK1 candidate tag single nucleotide polymorphisms (SNPs) and three STK39 SNPs, and haplotype analysis was performed. Results showed that the allele A in rs1468326 was overrepresented in hypertensive patients versus control (53.4% vs 42.9%, P < 0.05). The multivariable‐adjusted odds ratio (OR) for hypertension among CA + AA genotypes carriers was 1.60 (95% CI: 1.02–2.62, P < 0.05), and they also had a higher systolic blood pressure (136.5 ± 28.6 vs 131.7 ± 24.8 mmHg, P < 0.05). However, the TT genotype ratio in rs6749447 was lower in hypertensives (5.4% vs 10.8%, P < 0.05), and the hypertension risk for the TT genotype carriers in rs6749447 decreased after adjustment (OR 0.49, 95% CI 0.19–0.95, P < 0.05). Subjects with haplotype AGACAGGAATCGT showed 1.57 times higher risk of hypertension (95% CI 1.02–2.41, P < 0.05). In conclusion, SNP rs1468326 of WNK1, rs6749447 of STK39, and WNK1 haplotype AGACAGGAATCGT were associated with hypertension in Tibetan individuals. Environ. Mol. Mutagen. 59:151–160, 2018. © 2017 Wiley Periodicals, Inc.     

血清miR-21在糖尿病肾病中的诊断价值

 目的：评价血清miR-21对糖尿病肾病的诊断价值,探讨糖尿病肾病诊断的分子标志物。方法：对25例糖尿病肾病患者、25例II型糖尿病患者A［尿微量白蛋白（UmAlb）＜1429 mg/L］、25例II型糖尿病患者B（UmAlb＞1429 mg/L）、25例糖尿病肾病引发的尿毒症患者及25例正常对照组的血清标本进行总RNA提取,并进行miR-21的实时荧光定量PCR检测,分析血清miR-21相对表达量与相关临床指标的关系,评估血清miR-21对糖尿病肾病的诊断效能。结果：miR-21在糖尿病肾病患者血清中的相对表达量显著低于正常对照组、糖尿病A组及B组,同时显著高于尿毒症组(均P＜001),糖尿病肾病患者血清miR-21水平与胱抑素C、UmAlb、UmAlb/尿肌酐呈显著负相关（P<001,P<005,P<005)。经logistic回归及ROC曲线分析,血清miR-21在糖尿病肾病患者与正常对照组、糖尿病A组、糖尿病B组、糖尿病A组＋正常对照组、糖尿病B组＋正常对照组和糖尿病A组＋糖尿病B组中诊断糖尿病肾病的曲线下面积（AUC）为0848(95%CI：0737~0959)、0896(95%CI：0812~0980)、0782(95%CI：0641~0922)、0838(95%CI：0743~0933)、0796(95%CI：0675~0917)和0808(95%CI：0704~0911),敏感性和特异性分别为800%和720%、720%和880%、720%和840%、760%和770%、760%和820%、700%和860%;在4组人群中诊断糖尿病肾病的AUC为0845(95%CI：0752~0939),敏感性和特异性分别为760%和773%。结论：血清miR-21可作为糖尿病肾病的分子诊断标志物。     

Clinical significance of joint detection of serum CEA,SCCA, and bFGF in the diagnosis of lung cancer

Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction.     

Pathological significance of epidermal growth factor receptor expression and amplification in human gliomas

Zhao L‐l, Xu K‐l, Wang S‐w, Hu B‐l & Chen L‐r
(2012) Histopathology  61, 726–736 Pathological significance of epidermal growth factor receptor expression and amplification in human gliomas Aims: To investigate epidermal growth factor receptor (EGFR) expression and amplification in gliomas and to assess their association with survival. Methods and results: Immunohistochemistry and fluorescence in‐situ hybridization were performed to analyse EGFR status in 158 cases of primary glioma. Kaplan–Meier survival and Cox regression analyses were performed to analyse the prognosis of patients. Overexpression of EGFR and expression of EGFR variant III (EGFRvIII) were found in 102 cases (64.6%) and 47 cases (29.7%), respectively. Overexpression of EGFR was significantly correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) (both P < 0.05). Expression of EGFRvIII was significantly correlated with WHO grade, gender, age, and KPS (all P < 0.05). EGFR amplification was found in 46 cases (29.1%), and was significantly correlated with WHO grade, age, KPS and EGFR overexpression (all P < 0.05). Cox multifactor analysis showed that EGFR amplification was an independent unfavourable prognostic factor for human gliomas at all ages, and EGFRvIII was an independent prognostic factor in patients older than 60 years. Conclusions: EGFR amplification and EGFRvIII expression were associated with an unfavourable prognosis for patients of all ages, and for those older than 60 years, respectively. The differing significance of EGFR status in young and old glioma patients and its impact on prognosis needs further study.