Intrauterine exposure to long-chain perfluorocarboxylic acids (PFCAs) were associated with reduced primary bile acids in three-year-old children: Findings from a prospective birth cohort study.

Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding.

Per- and polyfluoroalkyl substances in ambient fine particulate matter in the Pearl River Delta, China: Levels, distribution and health implications.

Per- and polyfluoroalkyl substances (PFAS) have attracted worldwide attention as one of persistent organic pollutants; however, there is limited knowledge about the exposure concentrations of PFAS-contained ambient particulate matter and the related health risks. This study investigated the abundance and distribution of 32 PFAS in fine particulate matter (PM2.5) collected from 93 primary or secondary schools across the Pearl River Delta region (PRD), China. These chemicals comprise four PFAS categories which includes perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkyl acid (PFAA) precursors and PFAS alternatives. In general, concentrations of target PFAS ranged from 11.52 to 419.72 pg/m3 (median: 57.29 pg/m3) across sites. By categories, concentrations of PFSAs (median: 26.05 pg/m3) were the dominant PFAS categories, followed by PFCAs (14.25 pg/m3), PFAS alternatives (2.75 pg/m3) and PFAA precursors (1.10 pg/m3). By individual PFAS, PFOS and PFOA were the dominant PFAS, which average concentration were 24.18 pg/m3 and 6.05 pg/m3, respectively. Seasonal variation showed that the concentrations of PFCAs and PFSAs were higher in winter than in summer, whereas opposite seasonal trends were observed in PFAA precursors and PFAS alternatives. Estimated daily intake (EDI) and hazard quotient (HQ) were used to assess human inhalation-based exposure risks to PFAS. Although the health risks of PFAS via inhalation were insignificant (HQ far less than one), sufficient attention should be levied to ascertain the human exposure risks through inhalation, given that exposure to PFAS through air inhalation is a long term and cumulative process.

Inspecting the structural characteristics of chiral drug penicillamine under different pH conditions using Raman optical activity spectroscopy and DFT calculations.

The investigation of the structural characteristics of chiral drugs in physiological environments is a challenging research topic, which may lead to a better understanding of how the drugs work. Raman optical activity (ROA) spectroscopy in combination with density functional theory (DFT) calculations was exploited to inspect the structural changes in penicillamine under different acid-base states in aqueous solutions. The B3LYP/aug-cc-PVDZ method was employed and the implicit solvation model density (SMD) was considered for describing the solvation effect in H2O. The conformations of penicillamine varied with pH, but penicillamine was liable to stabilize in the form of the PC conformation (the sulfur atom is in a trans orientation with respect to carboxylate) in most cases for both D- and L-isomers. The relationship between the conformations of penicillamine and the ROA peaks, as well as peak assignments, were comprehensively studied and elucidated. In the fingerprint region, two ROA couplets and one ROA triplet with different patterns were recognized. The intensity, sign and frequency of the corresponding peaks also changed with varying pH. Deuteration was carried out to identify the vibrational modes, and the ROA peaks of the deuterated amino group in particular are sensitive to change in the ambient environment. The results are expected not only to serve as a reference for the interpretation of the ROA spectra of penicillamine and other chiral drugs with analogous structures but also to evaluate the structural changes of chiral molecules in physiological environments, which will form the basis of further exploration of the effects of structural characteristics on the pharmacological and toxicological properties of chiral drugs.

Establishment and application of an artificial intelligence diagnosis system for pancreatic cancer with a faster region-based convolutional neural network.

BACKGROUND: Early diagnosis and accurate staging are important to improve the cure rate and prognosis for pancreatic cancer. This study was performed to develop an automatic and accurate imaging processing technique system, allowing this system to read computed tomography (CT) images correctly and make diagnosis of pancreatic cancer faster. METHODS: The establishment of the artificial intelligence (AI) system for pancreatic cancer diagnosis based on sequential contrast-enhanced CT images were composed of two processes: training and verification. During training process, our study used all 4385 CT images from 238 pancreatic cancer patients in the database as the training data set. Additionally, we used VGG16, which was pre-trained in ImageNet and contained 13 convolutional layers and three fully connected layers, to initialize the feature extraction network. In the verification experiment, we used sequential clinical CT images from 238 pancreatic cancer patients as our experimental data and input these data into the faster region-based convolution network (Faster R-CNN) model that had completed training. Totally, 1699 images from 100 pancreatic cancer patients were included for clinical verification. RESULTS: A total of 338 patients with pancreatic cancer were included in the study. The clinical characteristics (sex, age, tumor location, differentiation grade, and tumor-node-metastasis stage) between the two training and verification groups were insignificant. The mean average precision was 0.7664, indicating a good training effect of the Faster R-CNN. Sequential contrast-enhanced CT images of 100 pancreatic cancer patients were used for clinical verification. The area under the receiver operating characteristic curve calculated according to the trapezoidal rule was 0.9632. It took approximately 0.2 s for the Faster R-CNN AI to automatically process one CT image, which is much faster than the time required for diagnosis by an imaging specialist. CONCLUSIONS: Faster R-CNN AI is an effective and objective method with high accuracy for the diagnosis of pancreatic cancer. TRIAL REGISTRATION: ChiCTR1800017542; http://www.chictr.org.cn.

Deep neural network-assisted computed tomography diagnosis of metastatic lymph nodes from gastric cancer.

BACKGROUND: Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features. This study aimed to use deep neural networks for computed tomography (CT) diagnosis of perigastric metastatic lymph nodes (PGMLNs) to simulate the recognition of lymph nodes by radiologists, and to acquire more accurate identification results. METHODS: A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks (FR-CNN) deep learning. The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy. Similarly, 1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above. The same 6000 gastric cancer CT images were used for the verification, according to which the diagnosis results were analyzed. RESULTS: In the initial group, precision-recall curves were generated based on the precision rates, the recall rates of nodule classes of the training set and the validation set; the mean average precision (mAP) value was 0.5019. To verify the results of the initial learning group, the receiver operating characteristic curves was generated, and the corresponding area under the curve (AUC) value was calculated as 0.8995. After the second phase of precise learning, all the indicators were improved, and the mAP and AUC values were 0.7801 and 0.9541, respectively. CONCLUSION: Through deep learning, FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800016787; http://www.chictr.org.cn/showproj.aspx?proj=28515.

Artificial intelligence system of faster region-based convolutional neural network surpassing senior radiologists in evaluation of metastatic lymph nodes of rectal cancer.

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION: www.chictr.org.cn (No. ChiCTR-DDD-17013842).

Nitric oxide potentiates oligosaccharide-induced artemisinin production in Artemisia annua hairy roots.

The purpose of the present study was to characterize the generation of nitric oxide (NO) in Artemisia annua roots induced by an oligosaccharide elicitor (OE) from Fusarium oxysporum mycelium and the potentiation role of NO in the elicitation of artemisinin accumulation. The OE (0.3 mg total sugar/mL) induced a rapid production of NO in cultures, which exhibited a biphasic time course, reaching the first plateau within 1.5 h and the second within 8 h of OE treatment. Artemisinin content in 20-day-old hairy roots was increased from 0.7 mg/g dry wt to 1.3 mg/g dry wt by using the OE treatment for 4 d. In the absence of OE, the NO donor sodium nitroprusside (SNP) at 10, 50 microM and 100 microM enhanced the growth of hairy roots, but had no effect on artemisinin synthesis. The combination of SNP with OE increased artemisinin content from 1.2 mg/g dry wt to 2.2 mg/g dry wt, whereas the maximum production of artemisinin in cultures was 28.5 mg/L, a twofold increase over the OE treatment alone. The effects of SNP on the OE-induced artemisinin were suppressed strongly by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). The results suggest that NO can strongly potentiate elicitor-induced artemisinin synthesis in A. annua hairy roots.

Classification of gastric pit patterns by confocal endomicroscopy.

BACKGROUND: Confocal endomicroscopy is a newly developed endoscopic imaging technology that produces 1000-fold magnification cross-sectional images of the GI surface and subsurface tissue during routine endoscopy. The gastric pit patterns identified by confocal endomicroscopy and correlation with histopathologic examination have not yet been established. OBJECTIVE: Our purpose was to explore the appearance of various kinds of gastric pits and clarify the relationship between gastric pit patterns and the histopathologic findings. DESIGN: Descriptive study. SETTING: Qilu Hospital, Shandong University, Jinan, China. PATIENTS: A total of 132 consecutive patients underwent confocal endomicroscopy after 7 healthy volunteers had been examined in vivo and 10 samples resected from 10 patients with gastric cancer had been examined ex vivo by use of confocal endomicroscopy. The confocal images obtained from the 132 patients were compared with the histopathologic findings of the biopsy specimens from the corresponding confocal imaging sites in a prospective and blinded fashion. MAIN OUTCOME MEASUREMENTS: The relationship between the pit patterns and the histopathologic findings. RESULTS: Gastric pit patterns were classified into 7 types. Normal mucosa with fundic glands mainly showed type A (round pits), and corporal mucosa with histologic gastritis showed type B (noncontinuous short rod-like); normal mucosa with pyloric glands mainly showed type C (continuous short rod-like), and antral mucosa with histologic gastritis showed type D (elongated and tortuous branch-like). Goblet cells were easily distinguished by confocal endomicroscopy in intestinal metaplasia mucosa, which showed type F. The sensitivity and specificity of the type E pattern for predicting gastric atrophy were 83.6% and 99.6%, respectively. Corresponding values of the type G pattern for predicting gastric cancer were 90.0% and 99.4%. LIMITATIONS: No data on interobserver and intraobserver variability. CONCLUSIONS: The patterns of gastric pits identified by confocal endomicroscopy correlate well with the histopathologic findings. Confocal endomicroscopy may prove useful in predicting histopathologic diagnoses during routine endoscopic procedures.

Confocal endomicroscopy for in vivo detection of microvascular architecture in normal and malignant lesions of upper gastrointestinal tract.

BACKGROUND AND AIM: Confocal laser endomicroscopy allows subsurface analysis of gastrointestinal mucosa during ongoing endoscopy. The present study assessed the feasibility of in vivo detecting superficial vascular architecture by confocal endomicroscopy in normal upper gastrointestinal mucosa and malignant lesions. METHODS: Early gastric cancer in eight patients, superficial esophageal carcinoma in six patients, and asymptomatic normal control in 10 patients were studied by confocal endomicroscopy. The characteristic of endomicroscopic microvascular architecture from normal and malignant mucosa was described and images were evaluated. RESULTS: Confocal endomicroscopy enabled clear visualization of the vascular networks of gastroesophageal mucosa. Honeycomb-like and coil-shaped regular microvascular architecture surrounding gastric pits were visible in the normal gastric body and antrum, respectively. Differentiated gastric cancerous mucosa showed hypervascularity and various caliber microvessels with irregular shapes. Undifferentiated gastric cancers disclosed a hypovascularity and irregular short branch vessels. Normal squamous epithelium had regular intraepithelial papillary capillary loops (IPCLs) directed toward the luminal surface. In superficial esophageal squamous carcinoma, dilated IPCLs were visible at the upper layer of the squamous mucosa. In esophageal adenocarcinoma, abnormal microvascular architecture showed tortuous and various calibers blood vessels. Of all the images, 41% were graded as good quality. The mean kappa value for interobserver agreement for the prediction of cancerous mucosa was 0.792. CONCLUSIONS: Confocal laser endomicroscopy system could yield very clear images of superficial microvascular network in the gastroesophageal mucosal layer both in malignant and normal mucosa. Endomicroscopic observation of vascular architecture may be of assistance in the identification of early gastroesophageal cancers.

A study on the effects of temperature and volume fraction on thermal conductivity of copper oxide nanofluid.

By using copper oxide nanofluid fabricated by the self-made Submerged Arc Nanofluid Synthesis System (SANSS), this paper measures the thermal conductivity under different volume fractions and different temperatures by thermal properties analyzer, and analyzes the correlation among the thermal conductivity, volume fraction, and temperature of nanofluid. The CuO nanoparticles used in the experiment are needle-like, with a mean particle size of about 30 nm. They can be stably suspended in deionized water for a long time. The experimental results show that under the condition that the temperature is 40 degrees C, when the volume fraction of nanofluid increases from 0.2% to 0.8%, the thermal conductivity increment of the prepared nanofluid towards deionized water can be increased from 14.7% to 38.2%. Under the condition that the volume fraction is 0.8%, as the temperature of nanofluid rises from 5 degrees C to 40 degrees C, the thermal conductivity increment of the prepared nanofluid towards deionized water increases from 5.9% to 38.2%. Besides, the effects of temperature change are greater than the effects of volume fraction on the thermal conductivity of nanofluid. Therefore, when the self-made copper oxide nanofluid is applied to the heat exchange device under medium and high temperature, an optimal radiation effect can be acquired.

[Confocal endomicroscopy for differential diagnosis of indented gastric lesions].

OBJECTIVE: Confocal endomicroscope (CEM) is a newly developed endoscope based on the integration of a confocal laser scanning microscope at the distal tip of a conventional video endoscope. It can visualize living tissue at a cellular level. The aim of the present study was to assess the value of CEM for prediction of the histopathology of gastric depressed-type lesions during endoscopy. METHODS: Forty-three patients with gastric depressed-type lesions underwent CEM and 51 depressed-type lesions were examined. Confocal diagnosis was made according to cellular and gastric pit morphology and compared with conventional histopathologic findings of corresponding biopsy specimens from the observed sites in a prospective and double-blinded fashion. RESULTS: The marginal and/or middle areas of every depressed-type lesion were examined by confocal imaging and a total of 4872 confocal images were obtained from 172 locations. Fluorescein sodium aided CEM to yield clear fluorescent images in vivo which allowed detailed analysis of surface and subsurface cellular and gastric pit architecture. A total of 46 biopsy specimens from 19 patients were diagnosed as gastric cancer. Confocal images had a sensitivity of 95.7%, a specificity of 97.6%, and accuracy of 97.1% for gastric cancer. CONCLUSIONS: CEM can provide virtual histopathology of gastric cancer with high accuracy during endoscopy and it is of potential value for the differential diagnosis of gastric depressed-type lesions and early detection of gastric cancer.

Plasma and gastric mucosal 5-hydroxytryptamine concentrations following cold water intake in patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: The purpose of the present paper was to investigate the effects of cold water intake on 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in diarrhea-predominant irritable bowel syndrome (d-IBS) patients, and to observe the relationship between 5-HT and symptomatology. METHODS: The plasma 5-HT/5-HIAA concentrations at 0, 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following cold or warm water intake were investigated in 32 female subjects with d-IBS and 21 healthy female subjects. Gastric mucosal 5-HT under fasting conditions and following water intake were further investigated in 15 d-IBS patients and nine healthy subjects. Symptomatology was assessed throughout the study. RESULTS: The plasma 5-HT concentrations in IBS patients were significantly higher than those of controls at 30 min (P = 0.022), 60 min (P < 0.001), 90 min (P < 0.001), 120 min (P < 0.001) and 150 min (P = 0.001) after cold water intake. The peak plasma 5-HT/5-HIAA and area under the curve for 5-HT/5-HIAA were also higher in d-IBS patients (P < 0.001). Gastric mucosal 5-HT in d-IBS patients and controls did not show any significant differences both under fasting condition (P = 0.596) and after cold water intake (P = 0.426). Last, the d-IBS patients with symptoms had higher 5-HT concentration (P < 0.001) and there was a positive correlation (r = 0.714, P = 0.001)between the symptomatology and plasma 5-HT level. CONCLUSIONS: These data suggest that symptomatology following cold water intake may be associated with increased plasma 5-HT concentrations in female subjects with d-IBS.

[The role of NF-E2-related factor 2 in the induction of uridine 5'-diphosphate-glucuronosyltransferase 1A and its isoforms by epigallocatechin gallate in colon cancer cells].

OBJECTIVE: To investigate the role of human transcription factor NF-E2-related factor 2 (Nrf2) in the induction of the gene expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A and its isoforms by epigallocatechin gallate (EGCG). METHODS: (1) Human colon carcinoma cells Caco-2 and HT-29 were cultured. Immunocytochemistry, western blotting and confocal laser microscopy were used to detect the protein expression of Nrf2. Twenty samples of colon carcinoma with surrounding normal tissues were collected during endoscopic course. (2) RNA interference expression vector pSilencer 3.1-H1 was used to construct four Nrf2-trageting plasmids: pSilence-Nrf2-A, B, C, and D and a control pSilence-CON. Cells were transfected with pSilence-Nrf2 for 48 hours to observe the effects of transient transfection. Cells were stably transfected with pSilence-Nrf2-B for 4 weeks and re-named as Caco-2-siNrf2 and HT-29-siNrf2 (siNrf2 cells), and others stably transfected with blank plasmid pSilencer 3.1-H1 were used as controls. (3) EGCG was added into the culture fluid of cells before and after the stably transfection. RT-PCR was used to detect the mRNA expression of Nrf2, UGT1A, UGT1A8 and UGT1A10 in cells and the samples of human colon cancer tissue. RESULTS: (1) The expressions of UGT1A8 and UGT1A10 mRNA were significantly lower than that in the surrounding healthy mucosa. (2) The mRNA expression of Nrf2, UGT1A8, and UGT1A10 increased by 1.8-9.2 times after the addition of EGCG (all P < 0.05). Immunocytochemistry, western blotting and immunofluorescence demonstrated a significant increase of Nrf2 protein expression in the nucleus after treatment with EGCG. (3) SalIenzyme digestion and DNA sequencing confirmed that pSilence-Nrf2-A, B, C, and D and pSilence-CON were all successfully constructed. The inhibition rate of Nrf2 gene expression was above 80% 48 h after transfection with pSilence-Nrf2-B, and that was no significant difference after transfection with pSilence-CON (P > 0.05). There was specific inhibition of Nrf2 in Caco-2-siNrf2, HT-29-siNrf2 cells (both P < 0.01). (4) The basal levels of UGT1A8 and UGT1A10 mRNA expression in the Caco-2-siNrf2 and HT-29-siNrf2 cells were lower by 15%-65% in comparison with those in control, and the induction of genes by EGCG was largely attenuated in them (all P > 0.05). CONCLUSION: Nrf2 is localized in the cytoplasm of non-stimulated cells, and EGCG triggered its rapid nuclear accumulation. Suppression of Nrf2 gene expression results in down-regulation of the constructive expression of UGT genes and their induction by EGCG. EGCG induces the expression of UGT1A, UGT1A8 and UGT1A10 genes via a Nrf2-dependent mechanism.