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Background and Aims: There remains a need to develop a non‐invasive, accurate and easy‐to‐use tool to identify patients with non‐alcoholic steatohepatitis (NASH). Successful clinical and preclinical applications demonstrate the ability of quantitative ultrasound (QUS) techniques to improve medical diagnostics. We aimed to develop and validate a diagnostic tool, based on QUS analysis, for identifying NASH. Methods: A total of 259 Chinese individuals with biopsy‐proven non‐alcoholic fatty liver disease (NAFLD) were enrolled in the study. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. Radiofrequency (RF) data, raw data of iLivTouch, was acquired for further QUS analysis. The least absolute shrinkage and selection operator (LASSO) method was used to select the most useful predictive features. Results: Eighteen candidate RF parameters were reduced to two significant parameters by shrinking the regression coefficients with the LASSO method. We built a novel QUS score based on these two parameters, and this QUS score showed good discriminatory capacity and calibration for identifying NASH both in the training set (area under the ROC curve [AUROC]: 0.798, 95% confidence interval [CI] 0.731‐0.865; Hosmer‐Lemeshow test, P =.755) and in the validation set (AUROC: 0.816, 95% CI 0.725‐0.906; Hosmer‐Lemeshow test, P =.397). Subgroup analysis showed that the QUS score performed well in different subgroups. Conclusions: The QUS score, which was developed from QUS, provides a novel, non‐invasive and practical way for identifying NASH. [ABSTRACT FROM AUTHOR]

Background and Aim: Cytochrome P450 2E1 (CYP2E1) plays a role in lipid metabolism, and by increasing hepatic oxidative stress and inflammation, the upregulation of CYP2E1 is involved in development of nonalcoholic steatohepatitis (NASH). We aimed to explore the relationship between CYP2E1‐333A>T (rs2070673) and the histological severity of nonalcoholic fatty liver disease (NAFLD). Methods: We studied 438 patients with biopsy‐proven NAFLD. NASH was defined as NAFLD Activity Score ≥ 5 with existence of steatosis, ballooning, and lobular inflammation. CYP2E1‐333A>T (rs2070673) was genotyped by matrix‐assisted laser desorption ionization‐time of flight mass spectrometry. Serum cytokines related to inflammation were measured by the Bio‐plex 200 system to investigate possible mediating factors involved in the process. Results: The TA genotype of rs2070673 had a higher prevalence of moderate/severe lobular inflammation (27.6% vs 20.3% vs 13.3%, P < 0.01) and NASH (55.7% vs 42.4% vs 40.5%, P < 0.01) compared with the AA and TT genotypes, respectively. In multivariable regression modeling, the heterozygote state TA was associated with moderate/severe lobular inflammation (adjusted odds ratio: 2.31, 95% confidence interval 1.41–3.78, P < 0.01) or NASH (adjusted odds ratio: 1.82, 95% confidence interval 1.22–2.69, P < 0.01), independently of age, sex, common metabolic risk factors, and presence of liver fibrosis. Compared with no‐NASH, NASH patients had significantly higher levels of serum interleukin‐1 receptor antagonist, interleukin‐18, and interferon‐inducible protein‐10 (IP‐10), whereas only IP‐10 was increased with the rs2070673 TA variant (P = 0.01). Mediation analysis showed that IP‐10 was responsible for ~60% of the association between the rs2070672 and NASH. Conclusions: The TA allele of rs2070673 is strongly associated with lobular inflammation and NASH, and this effect appears to be largely mediated by serum IP‐10 levels. [ABSTRACT FROM AUTHOR]

Uterine fibroids (UFs) are the most common benign neoplasms, but their pathogenesis is not completely understood. Thus far, alterations in the mitochondrial DNA (mtDNA) content and the mtDNA 4977‐bp deletion level in UFs, as well as the corresponding nontumorous tissue, have remained elusive. To test whether large mtDNA deletions and mtDNA content are involved in the pathogenesis of UFs, a total of 309 UF tissues and 28 paired adjacent myometrium from 270 UF patients were enrolled for the analysis of large mtDNA deletions and mtDNA content through the use of nested PCR and qPCR techniques, respectively. In our samples, a 4977‐bp deletion was identified: 36 out of 309 UF tissues (11.56%) and 15 out of 28 (53.57%) paired adjacent myometrium were detected to harbor the 4977‐bp deletion. In addition, a novel 4838‐bp mtDNA deletion was identified in three UF tissues, and other different sizes of deleted fragments (4910, 4926, 5135‐bp) were also found in UFs for the first time. Furthermore, older age was significantly associated with an mtDNA large deletion in the paired adjacent myometrium. We also found that increased mtDNA content and higher expression of ND1 occurred in solitary fibroids compared to adjacent myometrium. In conclusion, we identified a lower frequency of mtDNA large deletions and some novel large deletion in UFs for the first time. Furthermore, there was a general increase of mtDNA copy number during solitary UF development. Although the definite mechanism by which mtDNA was altered is supposed to be further confirmed, it will be helpful for further studies on the pathological mechanism of UFs. [ABSTRACT FROM AUTHOR]

Urinary biopterin (Bio) and neopterin (Neo) are important markers for clinical diagnosis of hyperphenylalaninemia. Herein, we developed a high‐throughput analysis method based on electrospray ionization mass spectrometry (ESI‐MS) with polymer tips for the rapid quantitative detection of Bio and Neo in clinical urine samples. Different polymer tips were investigated. It is found that the best detection sensitivity was achieved with hydrophobic polymer tip, ie, polyethylene tips. The high‐throughput polymer tip‐ESI‐MS method allowed a rapid analysis speed at ~40 seconds per sample. The limits of quantification (LOQ) (S/N ≥ 10) for the detection of Bio and Neo were improved to be 5.0 ng/mL. Acceptable relative standard deviation (RSD) values for Neo and Bio were measured to be 12.2% and 13.4% for direct measurement of Bio and Neo in raw urine samples, respectively. Furthermore, Bio and Neo were directly quantified from 18 clinical urine samples by presented method. The ratios of urinary Bio‐to‐Neo were analyzed for diagnosis of hyperphenylalaninemia. The results demonstrated that the present polymer tip‐ESI‐MS method is a promising strategy for the rapid analysis of clinical samples. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether imaging and clinicopathologic features could predict false‐positive axillary ultrasound (US) results in the selection of patients with breast cancer who had a heavy axillary tumor burden (≥3 tumor‐involved nodes). Methods: Among 788 patients with histologically confirmed invasive breast cancer at Ruijin Hospital from October 2014 to September 2015, 162 patients (cT1‐T2, cN0) with 167 axillae had suspicious axillary US findings. Ultrasound findings were considered suspicious for metastasis if cortical thickening of greater than 3 mm or effacement of the fatty hilum was present. The false‐positive rate of suspicious axillary US results for identifying 3 or more positive lymph nodes in the final pathologic examination was calculated. Univariate and multivariate analyses were used to evaluate imaging and clinicopathologic factors related to the false‐positive results. Results: Axillary US showed a false‐positive rate of 60.5% (101 of 167) in the patients with breast cancer and a heavy nodal burden. By logistic regression analyses, we found false‐positive axillary US results more frequently in patients who had a T1 stage tumor (P = .005), an estrogen receptor/progesterone receptor–negative tumor (P < .001), solitary suspicious nodes identified on axillary US (P < .001), and a cortical thickness of the most suspicious lymph node of 3.5 mm or less (P = .015). Conclusions: Imaging and clinicopathologic features can be used to identify axillae with less than 3 metastatic nodes in patients with early‐stage breast cancer who have positive axillary US results. In the post–American College of Surgeons Oncology Group Z0011 trial era, conducting a secondary evaluation either clinically or by axillary imaging before the use of a US‐guided biopsy of suspicious nodes can potentially avoid the additional morbidity of axillary lymph node dissection and reduce the preoperative workload. [ABSTRACT FROM AUTHOR]

The determination of pesticide residues is an indispensable task in controlling food safety and environment protection. Carbendazim is one of the extensive uses of pesticides in the agricultural industry. In this study, a simple method utilizing syringe filter has been applied as electrospray ionization emitter for mass spectrometric identification and quantification of carbendazim in complex matrices including soil, natural water, and fruit juice samples, which contain many insoluble materials. With online syringe filter of the complex samples, most of insoluble materials such as soil were excluded in spray ionization process due to the filter effect, and analytes were subsequently sprayed out from syringe needle for mass spectrometric detection. The pore sizes of filters and diameters of syringe needles also were investigated. The analytical performances, including the linear range (1-200 ng·mL-1), limit of detection (0.2-0.6 ng·mL-1, S/N > 3), limit of quantitation (3.5-8.6 ng·mL-1, S/N > 10), reproducibility (6.4%-12.5%, n = 6), and recoveries (72.1%-91.0%, n = 6) were well acceptable for direct analysis of raw samples. Matrix effect for detection of carbendazim in soil samples also was experimentally investigated. This study demonstrated that syringe filter needle coupled with electrospray ionization mass spectrometry is a simple, efficient, and sensitive method for detection of pesticide residues in water, soil, and fruit juice for risk assessment. [ABSTRACT FROM AUTHOR]

Objectives: Ultrasound (US)‐guided fine‐needle aspiration cytology (FNAC) is able to identify patients with extensive node involvement before surgery. In this study, we aimed to establish the optimal US criterion to identify abnormal lymph nodes on US‐guided FNAC for detection of patients with 3 or more metastatic axillary nodes. Methods: A total of 445 axillae from 443 patients with histologically confirmed invasive breast cancer (cT1–2 cN0) were examined with US at Ruijin Hospital from August 2013 to August 2014. Ultrasound‐guided FNAC was performed on suspicious nodes when the cortex was eccentrically or concentrically thickened to greater than 2 mm; 269 axillae (60.4%) met the criterion and underwent US‐guided FNAC. We retrospectively analyzed the US characteristics of axillary lymph nodes, the US‐guided FNAC results, and the extent of axillary nodal involvement. For diagnostic performance, the sensitivity, specificity, and receiver operating characteristic curves were obtained. Results: Eighty‐six patients (19.4%) were confirmed to have 3 or more positive lymph nodes by pathologic analysis. There was a significant association between the morphologic change in the most suspicious node and the extent of axillary nodal involvement (P <.001). When we applied the cutoff point (cortical thickness >3.5 mm) at which the maximal sum of sensitivity and specificity for diagnosis of 3 or more axillary lymph node metastases was achieved, we found that the sensitivity and specificity were 75.6% and 82.7%, respectively. When combining this criterion with US‐guided FNAC of the most suspicious nodes, the sensitivity and specificity were 64.2% and 94.5%, and 36.1% of cases could be spared an unnecessary 1‐step axillary lymph node dissection. Conclusions: Cortical thickness of greater than 3.5 mm in the most suspicious nodes is appropriately predictive of patients with 3 or more tumor‐involved axillary nodes. When this criterion for US‐guided FNAC was adopted, a group of patients with 1 or 2 metastatic nodes could be spared unnecessary 1‐step axillary lymph node dissection. [ABSTRACT FROM AUTHOR]

Weekly PCb (paclitaxel + carboplatin) in neoadjuvant chemotherapy (NCT) for breast cancer has a high pathological complete remission (pCR) rate. The present study was to identify pCR predictive biomarkers and to test whether integrating candidate molecular biomarkers can improve the pCR predictive accuracy. Ninety-one breast cancer patients treated with weekly PCb NCT were retrospectively analyzed. Eleven candidate molecular biomarkers (Tau, β-tubulin III, PTEN, MAP4, thioredoxin, multidrug resistance-1, Ki67, p53, Bcl-2, BAX, and ERCC1) were detected by immunohistochemistry in pre-NCT core needle biopsy specimens. We analyzed the relationship between these biomarkers and pCR. Univariate analysis showed that estrogen receptor, progesterone receptor, molecular classification (clinicopathological markers), and Tau, β-tubulin III, p53, Bcl-2, ERCC1 (candidate molecular biomarkers) expression were associated with pCR rate; however, multivariate analysis revealed that only β-tubulin III, Bcl-2, and ERCC1 were independent pCR predictive factors. Patients with β-tubulin III negative, Bcl-2 negative, or ERCC1 negative tumors were associated with higher pCR rate, with OR (odds ratios) 6.03 (95% confidence interval [CI], 1.44-25.24, P = 0.014), 7.54 (95% CI, 1.52-37.40, P = 0.013), and 4.09 (95% CI, 1.17-14.30, P = 0.028), respectively. To compare different logistic regression models, built with different combinations of these variables, we found that the model integrating routine clinical and pathological variables, as well as the β-tubulin III, Bcl-2, ERCC1 molecular biomarkers had the highest pCR predictive power. The area under the ROC curve for this model was 0.900 (95% CI, 0.831-0.968), indicating that it deserves further investigation. Trial name: Weekly Paclitaxel Plus Carboplatin in Preoperative Treatment of Breast Cancer. ( Cancer Sci 2012; 103: 262-268) [ABSTRACT FROM AUTHOR]