Priority list of potential endocrine-disrupting chemicals in food chemical contaminants: a docking study and in vitro/epidemiological evidence integration.

Diet is an important exposure route of endocrine-disrupting chemicals (EDCs), but many unfiltered potential EDCs remain in food. The in silico prediction of EDCs is a popular method for preliminary screening. Potential EDCs in food were screened using Endocrine Disruptome, an open-source platform for inverse docking, to predict the binding probabilities of 587 food chemical contaminants with 18 human nuclear hormone receptor (NHR) conformations. In total, 25 contaminants were bound to multiple NHRs such as oestrogen receptor α/ß and androgen receptor. These 25 compounds mainly include pesticides and per- and polyfluoroalkyl substances (PFASs). The prediction results were validated with the in vitro data. The structural features and the crucial amino acid residues of the four NHRs were also validated based on previous literature. The findings indicate that the screening has good prediction efficiency. In addition, the epidemic evidence about endocrine interference of PFASs in food on children was further validated through this screening. This study provides preliminary screening results for EDCs in food and a priority list for in vitro and in vivo research.

[Seroprevalence of Toxoplasma gondii and Toxocara infections among pregnant women in Hangzhou City].

OBJECTIVE: To investigate the prevalence of Toxoplasma gondii and Toxocara infections among pregnant women in Hangzhou City, so as to provide baseline data for decreasing birth defects and improving the population quality. METHODS: A total of 235 pregnant women receiving prenatal diagnosis at the First People's Hospital of Yuhang District during the period between February 2018 through December 2019 were recruited as the observation group, and 235 age-matched, non-pregnant healthy women at the same hospital during the same period served as the control group. The subjects'medical records were captured from the hospital management information system. Blood samples were collected from the observation and control groups and detected for the presence of IgG antibodies against T. gondii and Toxocara using an enzyme-linked immunosorbent assay (ELISA). The seroprevalence of the IgG antibodies against T. gondii and Toxocara was compared between the observation and control groups. RESULTS: The subjects in the observation group had a mean age of 26.5 ± 4.3 years (range, 23 to 31 years), and gestational ages of 10 to 27 weeks, and the subjects in the control group had a mean age of 26.1 ± 5.7 years (range, 20 to 30 years). The seroprevalence rates of IgG antibodies against T. gondii (28.51% vs. 4.68%; χ2 = 34.85, P < 0.01) and Toxocara (24.26% vs. 5.11%; χ2 = 25.77, P < 0.01) were both significantly higher in the observation group than in the control group, and the seroprevalence of T. gondii and Toxocara co-infections was also significantly greater in the observation group than in the control group (13.19% vs. 2.13%; χ2 = 17.49, P < 0.01). CONCLUSIONS: The seroprevalence rates of T. gondii and Toxocara infections and their co-infections are all high among pregnant women in Hangzhou City. Screening of T. gondii and Toxocara infections is strongly recommended during pregnancy.

Low pretreatment PNI correlates with worse survival in patients with stage III/IV NSCLC who received chemotherapy.

The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) on the long-term survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. Data on nutritional parameters and clinicopathological characteristics [e.g., albumin, total protein, body mass index (BMI), eastern cooperative oncology group (ECOG) performance status, stage, pathology, treatment strategy] were analyzed and retrospectively correlated with overall survival (OS). The PNI was calculated based on the concentration of albumin and lymphocyte count [10 × albumin, (g/dl) + 0.005 × lymphocyte (count/mm3)]. A receiver operating characteristic curve (ROC) analysis was used to find the optimal cut-off value of PNI. Univariate and multivariate analyses were used to evaluate the prognostic value of PNI. A total of 186 patients met the inclusion criteria. The optimal cut-off value for PNI was 50.45. Compared with the parameters of the low PNI group (n=76), high PNI was significantly associated with adenocarcinoma type, stage III, better ECOG and comprehensive treatment modality. The univariate analysis demonstrated that OS was superior when PNI ≥50.45, albumin ≥35 g/l, platelet-lymphocyte ratio (PLR) ≥163 and ECOG <2, and when the patient received a comprehensive treatment modality. In the multivariate analysis, PNI, TNM stage and treatment strategy were identified as independent predictors of survival in this study. This retrospective study demonstrated that a low PNI was related to worse overall survival in patients with stage III/IV NSCLC who received platinum-based chemotherapy. These data provided a conceptual basis for further research on the clinical application of the PNI index for patients receiving chemotherapy for intermediate- and advanced-stage NSCLC.

[Surveillance of key parasitic diseases in Baise City from 2006 to 2015].

OBJECTIVE: To understand and master the infection status of key parasitic diseases in Baise City from 2006 to 2015, so as to provide evidence for the development and adjustment of the control strategy for parasitic diseases. METHODS: The relevant information of the final evaluation of the key parasitic diseases in 12 counties (cities and districts) of Baise City from 2006 to 2015 was collected, and analyzed. RESULTS: During the period of 2006-2015, a total of 20 654 person-times were investigated for parasitic diseases in Baise City and 1 147 persons were infected, with an average infection rate of 5.55%. In 2006, the infection rate was the highest (28.67%, 362/1 254), while the lowest was in 2013 (2.08%, 44/2 113). The infection rate of Clonorchis sinensis was the highest, and the infection rate of Ascaris lumbricoides was the second. The infection rates of the males and females were 5.35% (631/11 795) and 5.82% (516/8 859) respectively, with no significant difference between them (χ2 = 2.175, P > 0.05). The highest infection rate existed in the 40-49 years group, the rural residents, the farmers and the crowd with the educational level of senior high middle school or above. CONCLUSIONS: The infection rate of parasitic diseases presents a decline trend overall in Baise City from 2006 to 2013, however it rebounded in 2014 and 2015. The next step is to strengthen the prevention and control of parasitic diseases by promoting health education, regular insect repellent, and fecundity management.

Serial T-SPOT.TB in household contacts of tuberculosis patients: a 6-year observational study in China.

BACKGROUND: Screening tuberculosis (TB) contacts is a priority for TB control; however, it remains inadequate in most regions of China.OBJECTIVE: To investigate the progression of latent TB infection (LTBI) using the interferon-gamma release assay (IGRA) in contacts of active TB patients.DESIGN: This longitudinal prospective observational study included 159 household contacts aged ≥14 years without preventive treatment who were followed up for 6 years to compare their conversion and reversion rates using the T-SPOT®.TB IGRA to diagnose LTBI.RESULTS: Among the 159 household contacts, LTBI positivity was 47.5%. Age was independently associated with LTBI (OR 3.6, 95%CI 1.81-7.14; P = 0.00). T-SPOT.TB conversion rates were respectively 29.4% and 18.8% at 3- and 6-year follow-up. The reversion rates were 9.4% of contacts during the 3-year follow-up period, which increased to 38.2% at the 6-year follow-up. A decreasing trend in spot-forming cells on T-SPOT.TB was observed in most patients at the 6-year follow-up.CONCLUSION: LTBI prevalence among household contacts was relatively high, particularly in elderly patients. Furthermore, serial IGRA testing was highly dynamic; however, this overall trend gradually decreased over time, even if preventive therapy was not prescribed.

[Clinicopathological features and prognosis of 488 patients with neuroendocrine tumors].

Objective: To investigate the clinicopathological features and prognosis of patients with neuroendocrine tumors (NETs). Methods: The clinicopathologic data of enrolled patients with NETs between October 2012 and October 2017 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Among the 488 NETs patients, the average age was (51.0±15.8) years, and the sex ratio (male/female) was 1∶1.1. Of the NETs, 370 were located in the digestive system (75.8%), 63 were pulmonary (12.9%), 14 were mediastinal (2.9%), 7 were of unknown primary origin (1.4%), and 34 were located in other sites (7.0%). Among the NETs, the pancreas, rectum and stomach were the most common sites. In the digestive system NETs, the most common tumor grade was G1 (190 cases, 51.4%), followed by G2 (143 cases, 38.6%) and NET-G3 (37 cases, 10.0%). In pulmonary NETs, typical and atypical carcinoid tumors was 47.6% and 52.4%, respectively. There were 310 patients at stage Ⅰ/Ⅱ, 53 at stage Ⅲ, 69 at stage Ⅳ and 56 at stage undiagnosed, respectively. The relationships among age, stage, grade, metastasis, treatment and prognosis were analyzed. All these factors could influence the survival rate of NET patients. Multivariate Cox analysis showed that age (>50 years old) (HR=2.831, 95%CI:1.414-7.029, P=0.025) and distant metastasis (HR=10.208, 95%CI:4.110-25.355, P<0.001) were independent risk factors. Conclusions: The most common primary sites of NETs are the pancreas, rectum, and stomach. Age and distant metastasis are independent risk factors for the prognosis of NETs.

[Functional lateralization of major Chinese language cortex for presurgical evaluation in neurosurgery].

Objective: To investigate the functional lateralization of major Chinese language cortex in patients with cerebral arteriovenous malformation (AVM) in dominant hemispheric via functional magnetic resonance imaging (fMRI). Methods: Nine right-handed normal volunteers and fourteen patients with cerebral AVM in dominant hemisphere diagnosed in Beijing Tiantan Hospital between December 2017 and June 2018 were included. Three language tasks (semantic judgment, word reading, and listening comprehension) were applied to activate language areas. Lateralization index (LI) was used to show the dominant hemisphere. Results: In the control group, right-sided lateralization of BOLD signal activations was observed in 0/27 (0%) of the language tasks. While in the AVM patients, right-sided lateralization of BOLD signal activations was observed in 8/42 (19%) language tasks. The difference was statistically significant (χ(2)=5.73, P=0.019). Conclusions: The dominant hemisphere of different language tasks may be different in patients with cerebral lesions. Compared with normal controls, patients with cerebral AVM in dominant hemispheric are more likely to have right-sided lateralization of language cortex.

Correction: RCP induces Slug expression and cancer cell invasion by stabilizing ß1 integrin.

Following the publication of this article the authors noted that images were inadvertently duplicated in Fig. 1b. The corrected Fig. 1 can be found in the associated Correction. The conclusions of this paper are not affected. The authors sincerely apologize for this error. This error has not been corrected in the HTML or PDF of the original Article.

[Characterization and uncertainty evaluation of aqueous reference materials for cholesterol].

Objective: Characterization and evaluation of the uncertainty of the reference materials of cholesterol in aqueous solution. Methods: The certified reference material GBW09203b was weighed accurately and dissolved into methyl cyclodextrin aqueous solution to prepare six kinds of candidate reference materials of cholesterol according to the concentration. The materials were tested for homogeneity and stability using routine methods and were evaluated the uncertainty derived from the inhomogeneity and instability. The uncertainty due to measurement was derived from the purity of the raw material, the weighing and the density measurement. The certified values and expanded uncertainties were calculated according to the ISO Guide. The expanded uncertainty of the certified value was the combination of standard uncertainty of measurement, inhomogeneity and instability. The coverage factor, k, was determined from the Student's t-distribution corresponding to the calculated effective degrees of freedom and 95% level of confidence. Results: It showed that the six candidate reference materials were homogeneous and were tested to be stable for at least 1 year at -70 ℃ and -20 ℃ using the isochronous stability study. The relative uncertainties due to the inhomogeneity were 0.14%, 0.11%, 0.13%, 0.47%, 0.39% and 0.11%. The relative uncertainty due to the instability was 0.25% at -70 ℃. The uncertainties of measurement were 0.06%, 0.05%, 0.05%, 0.05%, 0.05% and 0.05%.The certified values (reference value ± expanded uncertainty, mmol/L) were as follows: (0.651±0.004), (1.310 ±0.007), (2.574±0.015), (5.210±0.055), (7.710±0.072), (10.242±0.056) mmol/L. Conclusions: Six kinds of certified reference materials for cholesterol in aqueous solution have been prepared, which were homogeneity, stable and reliable. It showed that the uncertainty of measurement was very small compared with the uncertainty due to inhomogeneity and instability.

RCP induces Slug expression and cancer cell invasion by stabilizing ß1 integrin.

Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes ß1 integrin leading to increased ß1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing ß1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion. Conversely, ectopic expression of ß1 integrin was sufficient to induce Slug expression. Pharmacological inhibition of integrin linked kinase (ILK), EGFR and NF-κB, as well as transfection of a dominant-negative mutant of Ras (RasN17), significantly inhibited RCP-induced Slug expression and cancer cell invasion. Strikingly, ectopic expression of RCP was sufficient to enhance metastasis of ovarian cancer cells to the lung. Collectively, we demonstrate a mechanism by which RCP promotes cancer cell aggressiveness through sequential ß1 integrin stabilization, activation of an ILK/EGFR/Ras/NF-κB signaling cascade and subsequent Slug expression.

HLJ1 is an endogenous Src inhibitor suppressing cancer progression through dual mechanisms.

HLJ1 (DNAJB4), a DNAJ/Hsp40 chaperone, has emerged as a novel prognostic marker in lung cancers; however, the molecular contribution and functionality in neoplastic diseases remain to be established. This study demonstrated that HLJ1 inhibits epithelial-mesenchymal transition in vitro and reduces lung cancer metastasis in vivo. Using shRNA silencing and ectopic expression of HLJ1, we found that HLJ1 not only suppresses catalytic activity of Src but also downregulates the formation of oncogenic complexes associated with the EGFR, FAK and STAT3 signaling pathways. A screen of specimens from HLJ1-knockout mice and lung cancer patients validated that HLJ1 expression is inversely correlated with Src activity. Mechanistically, HLJ1 protein directly bound to catalytic and protein-binding domains of Src through its amino acid Y172 and the P301/P304 motif. Following Src-induced HLJ1 phosphorylation at Y172, HLJ1-Src interaction was elevated, resulting in Src inhibition and malignancy suppression. Interestingly, both Src-binding regions also occurred in other DNAJB family members and contributed to anti-invasive activities of DNAJB proteins. We conclude that HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. This HLJ1-Src complex might provide a promising molecular model for developing new anticancer strategies.

[Diffusion tensor imaging of the central auditory system in the elderly].

Objective:To evaluate the changes in the central auditory system of presbycusis by applying auditury brainstem response (ABR) and diffusion tensor imaging (DTI). Method:A total of twenty-five elderly subjects with expressed presbycusis, eight elderly subjects with normal hearing and fifteen healthy volunteers as young controls were enrolled in the study. Each participant was examined using ABR and DTI. ABR measures were obtained from all the subjects. The fractional anisotropy (FA) was measured at two brain regions of the auditory pathway-the inferior colliculus (IC) and Heschl's gyrus. Result:Higher FA values were recorded at the left side of the Heschl's gyrus in all three groups (P<0.05). There were no significant differences between the left and right side of the ABR results and FA values of inferior colliculus in the three groups (P>0.05). Aging increased ABR peak latencies, yet did not change the Ⅰ-Ⅴ interpeak latency interval. Comparing with the elderly subjects with normal hearing group, the wave Ⅴ latencies of the presbycusis group were prolonged (P<0.05). Comparing with the healthy control group, the FA values of the IC were reduced in both of the elderly subjects with normal hearing group and the presbycusis group (P<0.05). No statistically differences were observed between the presbycusis group and the elderly subjects with normal hearing group in the FA values of the IC (P>0.05). Significant differences between all groups were found in the FA values of the Heschl's gyrus, with higher values in the elderly subjects with normal hearing group than in the presbycusis group and even higher values in the healthy control group than in the elderly subjects with normal hearing group (P<0.05). Conclusion:The results indicated that the age-related microstructural changes exist in the central part of the auditory system, which are more obvious in the patients with presbycusis.

Clinical efficacy of fiberoptic ductoscopy in combination with ultrasound-guided minimally invasive surgery in treatment of plasma cell mastitis.

OBJECTIVES: To analyze clinical efficacy between fiberoptic ductoscopy plus ultrasound-guided minimally invasive irrigation and lesion resection in treating plasma cell mastitis (PCM), aiming to provide clinical evidence for treating PCM. MATERIALS AND METHODS: 119 patients undergoing fiberoptic ductoscopy plus ultrasound-guided minimally invasive surgery in Ningxia People's Hospital were allocated into the breast duct irrigation group, and 95 counterparts receiving lesion resection in the Affiliated Hospital of Ningxia Medical University into the control group. Clinico-pathological characteristics and therapeutic effect were compared between two groups. RESULTS: The cure rate in the breast duct irrigation group was 98.31% (117/119), significantly higher than 90.53% in the control group (p < 0.05). In the breast duct irrigation group, overall treatment time was 20.13 days, significantly longer than 15.15 days in the control group (p < 0.05). During postoperative follow-up, no recurrence was observed, significantly lower compared with 48.8% (42/86) in the control group. The degree of satisfaction in the breast duct irrigation group was 95.79% (114/119), significantly higher compared with 74.74% (71/95) in the control group. CONCLUSIONS: Fiberoptic ductoscopy plus with ultrasound-guided minimally invasive drainage is a novel and effective treatment of PCM with high cure rate, low recurrence rate, slight pain, and effectively maintains breast integrity.

Slug is temporally regulated by cyclin E in cell cycle and controls genome stability.

The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.

The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.

Accuracy of vessel-encoded pseudocontinuous arterial spin-labeling in identification of feeding arteries in patients with intracranial arteriovenous malformations.

BACKGROUND AND PURPOSE: Identifying feeding arteries of intracranial AVMs is very important for preoperative evaluation. DSA remains the reference standard for diagnosis but is invasive. Our aim was to evaluate the diagnostic accuracy of vessel-encoded pseudocontinuous arterial spin-labeling in identifying feeding arteries of intracranial AVMs by using DSA as the criterion standard. MATERIALS AND METHODS: Eighteen patients with AVMs were examined with vessel-encoded pseudocontinuous arterial spin-labeling and DSA. Three postlabeling delays (postlabeling delay = 1, 1.3, and 1.6 seconds) were applied in 6 patients, and a single postlabeling delay (1 second) was applied in the remainder. Perfusion-weighted images were decoded into individual vascular territories with standard and relative tagging efficiencies, respectively. The supply fraction of each feeding artery to the AVM was calculated. The within-subject ANOVA was applied to compare supply fractions acquired across 3 postlabeling delays. Receiver operating characteristic analysis curves were calculated to evaluate the diagnostic accuracy of vessel-encoded pseudocontinuous arterial spin-labeling for identifying the feeding arteries of AVMs. RESULTS: There were no significant differences in supply fractions of the 3 major arteries to AVMs acquired with 3 postlabeling delays (P > .05). For vessel-encoded pseudocontinuous arterial spin-labeling with standard labeling efficiencies, the area under the receiver operating characteristic analysis curve was 0.942. The optimal cutoff of the supply fraction for identifying feeding arteries was 15.17%, and the resulting sensitivity and specificity were 84.62% and 93.33%, respectively. For vessel-encoded pseudocontinuous arterial spin-labeling with relative labeling efficiencies, the area under the receiver operating characteristic analysis curve was 0.957. The optimal cutoff of the supply fraction was 11.73%, which yielded an 89.74% sensitivity and 93.33% specificity. CONCLUSIONS: The contribution fraction of each feeding artery of the AVM can be reliably estimated by using vessel-encoded pseudocontinuous arterial spin-labeling. Vessel-encoded pseudocontinuous arterial spin-labeling with either standard or relative labeling efficiencies offers a high level of diagnostic accuracy compared with DSA for identifying feeding arteries.