Dietary Galacto-oligosaccharides Ameliorate Atopic Dermatitis-like Skin Inflammation and Behavioral Deficits by Modulating Gut Microbiota-Brain-Skin Axis.

Atopic dermatitis (AD), a chronic, highly pruritic, and inflammatory skin disorder, often coexists with psychiatric comorbidities including anxiety and depression, posing considerable challenges for treatment. The current research aims at evaluating the efficacy and potential therapeutic mechanism of galacto-oligosaccharides (GOS) on AD-like skin lesions and comorbid anxiety/depressive disorders. Macroscopical and histopathological examination showed that GOS could markedly relieve skin inflammation by decreasing the production of IgE, IL-4, IL-13, IFN-γ, and TNF-α and regulating the PPAR-γ/NF-κB signaling in DNFB-induced AD mice. Moreover, GOS significantly improved the anxiety- and depressive-like symptoms as mirrored by the behavior tests including FST, TST, OFT, and EZM through normalizing the neurotransmitter levels of 5-HT, DA, NE, and CORT in the brain. Mechanistically, by virtue of the high-throughput 16S rRNA gene sequencing and GC-MS techniques, GOS restructured the gut microbiota and specifically induced the proliferation of Lactobacillus and Alloprevotella, leading to an increase in the total content of fecal SCFAs, in particular acetate and butyrate. Pearson correlation analysis found a marked correlation among the altered gut microbiota/SCFAs, AD-associated skin manifestations, and comorbid behavioral phenotypes. Collectively, this work highlights that GOS is a promising strategy against both AD and associated depressive symptoms by modulating the gut microbiota-brain-skin axis.

Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice.

During cold exposure, activated brown adipose tissue (BAT) takes up a large amount of circulating glucose to fuel non-shivering thermogenesis and defend against hypothermia. However, little is known about the endocrine function of BAT controlling glucose homoeostasis under this thermoregulatory challenge. Here, we show that in male mice, activated BAT-derived extracellular vesicles (BDEVs) reprogram systemic glucose metabolism by promoting hepatic gluconeogenesis during cold stress. Cold exposure facilitates the selective packaging of miR-378a-3p-one of the BAT-enriched miRNAs-into EVs and delivery into the liver. BAT-derived miR-378a-3p enhances gluconeogenesis by targeting p110α. miR-378 KO mice display reduced hepatic gluconeogenesis during cold exposure, while restoration of miR-378a-3p in iBAT induces the expression of gluconeogenic genes in the liver. These findings provide a mechanistic understanding of BDEV-miRNA as stress-induced batokine to coordinate systemic glucose homoeostasis. This miR-378a-3p-mediated interorgan communication highlights a novel endocrine function of BAT in preventing hypoglycemia during cold stress.

Dual-response fluorescence sensing of H2PO4- and CO32- using AJP filter paper based on a pH-stable CdII-based luminescent metal-organic framework.

A new CdII-based luminescent metal-organic framework (LMOF) with the formula {[Cd(BIBT)(NDC)]·solvents}n (JXUST-32, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2NDC = 2,6-naphthalenedicarboxylic acid) was successfully synthesized by a solvothermal method. JXUST-32 shows a two-dimensional (4,4)-connected network and exhibits significant fluorescence red shift and slight enhancement for H2PO4- and CO32- sensing with detection limits of 0.11 and 0.12 µM, respectively. In addition, JXUST-32 has good thermal stability, chemical stability and recyclability. Significantly, JXUST-32 represents a fluorescence red-shift dual response MOF sensor for H2PO4- and CO32- detection and the analytes can be identified by the naked eye, aerosol jet printing filter paper, light-emitting diode beads and luminescent films.

Supramolecular self-assembly of robust, ultra-stable, and high-temperature-resistant viscoelastic worm-like micelles.

HYPOTHESIS: Worm-like micelles are susceptible to heating owing to the fast dynamic exchange of molecules between micelles. Inhibition of such exchange could afford robust worm-like micelles, which is expected to largely improve rheology properties at high temperatures. EXPERIMENTS: A cationic surfactant docosyl(trimethyl)azanium chloride (DCTAC) and a strongly hydrophobic organic counterion 3-hydroxy naphthalene-2-carboxylate (SHNC) were used for the worm-like micelles fabrication. The microstructure was characterized using cryogenic transmission electron microscopy and small-angle neutron scattering, and the interactions between DCTAC and SHNC were characterized using nuclear magnetic resonance spectroscopy. Rheometer was employed to measure the rheological properties of the solution. FINDINGS: SHNC/DCTAC at the molar ration of 1:2 forms ultra-stable worm-like micelles, whose viscosity remain stable at temperature up to 130 °C. SHNC is found to strongly adsorbs on DCTAC micelle with the orientation on the surface of micelle, keeping the naphthalene backbone entire penetration into the palisade layer while both carboxylic and hydroxyl groups protrude out of the micelle. With temperature increasing, this adsorption further strengthens, resulting in the growth contour length and accompanying the enhancement of rheological properties. One SHNC molecule and two DCTAC molecules are speculated to form a stable complex via multiple interactions including hydrophobic, cationic-π, and π-π interactions, which decreases the dynamic exchange of them between micelles. These findings are helpful to understand surfactant aggregates stability and assist the development of novel stable supramolecular nanostructures. Additionally, the excellent thermal stability of this worm-like micellar fluid makes it a potential high-temperature resistant clean fracturing fluid for deep oil reservoirs.

A clinical study of the effect of 3D reconstruction on exophthalmos after an operation on an old orbital wall fracture.

BACKGROUND: Orbital blowout fracture is common in ocular trauma. Accurate measurement of orbital volume after fracture is key in improving intraocular correction. OBJECTIVE: This study aims to explore the impact of 3D reconstruction technology in restoring normal exophthalmos in patients with old orbital wall fractures. METHODS: A total of 31 patients were randomly divided into an experimental group (n= 15) and a control group (n= 16). For orbital wall repair and reconstruction, the conventional group used the conventional surgical scheme, and the 3D group used 3D printing technology. RESULTS: There was no statistical difference between the preoperative mean extraocular muscle volume of the healthy eye and the affected eye. However, the mean orbital volume (24.76 vs 27.11, P= 0.005) and mean retrobulbar fat volume (17.53 vs 16.42, P= 0.006) were significantly different between the healthy eye and the affected eye. After an average follow-up of 16 weeks, the differences in pre- and post-surgery exophthalmos in the two groups were 0.42 ± 0.08 mm and 1.63 ± 0.51 mm, respectively. The difference between the two groups was statistically significant (t= 4.42, P= 0.003). The complications were not statistically different. CONCLUSION: Using 3D reconstruction technology preoperatively can significantly improve exophthalmos in patients with old orbital wall fractures.

Fructo-oligofructose ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions and psychiatric comorbidities in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus and eczema lesions and psychiatric comorbidities. The gut-brain-skin axis plays a pivotal role during AD development, which might suggest a novel therapeutic strategy for AD. The present study aims to uncover the protective effects and underlying mechanisms of fructo-oligofructose (FOS), a type of prebiotic, on AD-like skin manifestations and comorbid anxiety and depression in AD mice. RESULTS: Female Kunming mice were treated topically with 2,4-dinitrofluorobenzene (DNFB) to induce AD-like symptoms and FOS was administered daily for 14 days. The results showed that FOS could alleviate AD-like skin lesions markedly as evidenced by dramatic decreases in severity score, scratching bouts, the levels of immunoglobulin E (IgE) and T helper 1(Th1)/Th2-related cytokines, and the infiltration of inflammatory cells and mast cells to the dermal tissues. The comorbid anxiety and depressive-like behaviors, estimated by the forced swimming test (FST), the tail-suspension test (TST), the open-field test (OFT), and the zero maze test (ZMT) in AD mice, were significantly attenuated by FOS. Fructo-oligofructose significantly upregulated brain neurotransmitters levels of 5-hydroxytryptamine (5-HT) and dopamine (DA). Furthermore, FOS treatment increased the relative abundance of gut microbiota, such as Prevotella and Lactobacillus and the concentrations of short-chain fatty acids (SCFAs), especially acetate and iso-butyrate in the feces of AD mice. The correlation analysis indicated that the reshaped gut microbiome composition and enhanced SCFAs formation are associated with skin inflammation and behavioral alteration. CONCLUSION: Collectively, these data identify FOS as a promising microbiota-targeted treatment for AD-like skin inflammation and comorbid anxiety and depressive-like behaviors. © 2023 Society of Chemical Industry.

Selective recognition of Hg2+ ions in aqueous solution by a CdII-based metal-organic framework with good stability and vacant coordination sites.

A novel water-stable CdII-based metal-organic framework, namely {[Cd(BIBT)(TDC)]·2H2O}n (JXUST-28, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2TDC = 2,5-thiophenedicarboxylic acid), was synthesized using a mixed-ligand strategy. Structural analysis demonstrates that JXUST-28 exhibits a two-dimensional layer structure with 4-connected sql topology. Intriguingly, JXUST-28 presents good stability in boiling water (at least 5 days), common organic solvents and aqueous solutions with different pH values of 2-12 (more than 24 hours). Furthermore, fluorescence experiments revealed that JXUST-28 could sense Hg2+ ions in aqueous solution via a quenching effect with a detection limit of 0.097 µM. Meanwhile, JXUST-28 can also be regenerated at least 5 times to detect Hg2+ ions. In addition, light-emitting diode lamps, luminescent films, and test papers of JXUST-28 have been successfully developed for practical applications.

Analysis of Treatment Efficacy of Intense Pulsed Light (M22) for Meibomian Gland Dysfunction with Demodex Mites.

Objective: To investigate the effectiveness of intense pulsed light (M22) in treating patients with meibomian gland dysfunction (MGD) caused by demodex mites. Methods: A total of 100 patients (100 eyes) diagnosed with demodex mites through microscopic examination at Shanxi Bethune Eye Clinic between June 2021 and May 2023 were selected using convenience sampling. The patients were randomly divided into two groups: an experimental group (n=50) and a control group (n=50). The control group received comprehensive treatment consisting of artificial tears, warm compress, anti-inflammatory eye ointment, hypochlorous acid cleansing, okra cotton pad, and meibomian gland massage. In addition to the comprehensive treatment, the experimental group received intense pulsed light (M22) therapy. After 8 weeks of treatment, the mite clearance rate and cure rate of dry eye were measured for both groups. The recurrence rate of dry eye was also observed 4 weeks after discontinuing M22 treatment. Results: The experimental group achieved a mite clearance rate of 88.0%, while the control group had a rate of 58.0%, with a statistically significant difference (χ2 = 5.43, P = 0.017). Regarding the cure rate of dry eye, the experimental group showed a rate of 92.0%, while the control group had a rate of 82.0%, with a statistically significant difference (χ2 = 3.61, P = 0.021). In terms of the recurrence rate of dry eye, the experimental group exhibited a rate of 13.04%, while the control group had a rate of 26.83%, with a statistically significant difference (χ2 = 4.18, P = 0.016). Conclusion: Intense pulsed light (M22) demonstrated superior efficacy in eradicating demodex mites, treating dry eye, and maintaining the treatment's effectiveness compared to comprehensive treatment with medication in patients suffering from meibomian gland dysfunction with demodex mites.

Network analysis of anxiety and depression in the functionally impaired elderly.

Background: Evidence from previous studies has confirmed that functionally impaired elderly individuals are susceptible to comorbid anxiety and depression. Network theory holds that the comorbidity emerges from interactions between anxiety and depression symptoms. This study aimed to investigate the fine-grained relationships among anxiety and depression symptoms in the functionally impaired elderly and identify central and bridge symptoms to provide potential targets for intervention of these two comorbid disorders. Methods: A total of 325 functionally impaired elderly individuals from five communities in Xi'an, China, were recruited for our investigation. The GAD-7 and PHQ-9 were used to measure anxiety and depression, respectively. SPSS 22.0 software was used for descriptive statistics, and R 4.1.1 software was used for network model construction, expected influence (EI) evaluation and bridge expected influence (BEI) evaluation. Results: In the network, there were 35 edges (indicating partial correlations between symptoms) across the communities of anxiety and depression, among which the strongest edge was A1 "Nervousness or anxiety"-D2 "Depressed or sad mood." A2 "Uncontrollable worry" and D2 "Depressed or sad mood" had the highest EI values in the network, while A6 "Irritable" and D7 "Concentration difficulties" had the highest BEI values of their respective community. In the flow network, the strongest direct edge of D9 "Thoughts of death" was with D6 "Feeling of worthlessness." Conclusion: Complex fine-grained relationships exist between anxiety and depression in functionally impaired elderly individuals. "Uncontrollable worry," "depressed or sad mood," "irritable" and "concentration difficulties" are identified as the potential targets for intervention of anxiety and depression. Our study emphasizes the necessity of suicide prevention for functionally impaired elderly individuals, and the symptom "feeling of worthlessness" can be used as an effective target.

Molecular Mechanisms of Luteolin Against Atopic Dermatitis Based on Network Pharmacology and in vivo Experimental Validation.

Purpose: To undercover the underlying mechanisms of luteolin against atopic dermatitis (AD), clinically characterized by recurrent eczematous lesions and intense itching, based on network pharmacology, molecular docking and in vivo experimental validation. Methods: TCMSP, STITCH and SwissTargetPrediction databases were utilized to screen the corresponding targets of luteolin. Targets related to AD were collected from DisGeNET, GeneCards and TTD databases. PPI network of intersection targets was constructed through STRING 11.0 database and Cytoscape 3.9.0 software. GO and KEGG enrichment analysis were performed to investigate the critical pathways of luteolin against AD. Further, the therapeutic effects and candidate targets/signaling pathways predicted from network pharmacology analysis were experimentally validated in a mouse model of AD induced by 2, 4-dinitrofluorobenzene (DNFB). Results: A total of 31 intersection targets were obtained by matching 151 targets of luteolin with 553 targets of AD. Among all, 20 core targets were identified by PPI network topology analysis, including IL-6, TNF, IL-10, VEGFA, IL-4, etc., and molecular docking indicated that luteolin binds strongly to these core targets. KEGG pathway enrichment analysis suggested that the intersected targets were significantly enriched in IL-17 signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation, JAK/STAT signaling pathway, etc. The in vivo experiment validated that luteolin could alleviate AD-like skin symptoms, as evidenced by the lower SCORAD score, the reduced infiltration of mast cells and the recovery of skin barrier function. Furthermore, luteolin restored immune balance by regulating the production of Th1/Th2/Th17-mediated cytokines, which were both the predicted core targets. Moreover, luteolin inhibited the phosphorylation of JAK2 and STAT3 in the lesional skin. Conclusion: Together, the present study systematically clarifies the ameliorative effects and possible molecular mechanisms of luteolin against AD through the combination of network pharmacology and experimental validation, shedding light on the future development and clinical application of luteolin.

Autoantibody Against Ferritin Light Chain is a Serum Biomarker for the Detection of Liver Cirrhosis but Not Liver Cancer.

Purpose: Ferritin is a protein that plays an important role in iron metabolism, it consists of two subunits: heavy chain (FTH) and light chain (FTL). Elevated expression of FTL is observed in multiple malignancies. Recent studies have found that the frequency of circulating autoantibody against FTL (anti-FTL) increased significantly in hepatocellular carcinoma (HCC). The aim of this study is to verify circulating anti-FTL as a biomarker for the early detection of HCC. Patients and Methods: A total of 1565 participants were enrolled and assigned to two independent validation cohorts, including 393 HCC patients, 379 liver cirrhosis (LC) patients, 400 chronic hepatitis (CH) patients, and 393 healthy subjects. The concentration of serum anti-FTL was measured by indirect Enzyme-Linked Immunosorbent Assay (ELISA). Kruskal-Wallis test was used to compare anti-FTL concentrations between HCC group and three control groups. Percentile 95 of anti-FTL absorbance value of healthy group was selected as the cut-off value to calculate the positive rate in each group. The area under receiver operating characteristic curve (AUC) was used to quantitatively describe its diagnostic value. Results: The median concentration of anti-FTL in HCC patients was higher than that in CH patients and healthy subjects, but there was no difference between HCC patients and LC patients. Further analysis showed that there was no difference between early stage LC, advanced stage LC, Child-Pugh A HCC, Child-Pugh B HCC and Child-Pugh C HCC. The positive rate of anti-FTL was 12.2% (48/393) in HCC, 13.5% (51/379) in LC, 6.3% (25/400) in CH and 5.1% (20/393) in healthy subjects, respectively. The AUC of anti-FTL to distinguish LC from CH or healthy subjects were 0.654 (95% CI: 0.615-0.692) and 0.642 (95% CI: 0.602-0.681), respectively. Conclusion: Anti-FTL is not a biomarker for the early diagnosis of HCC due to specificity deficiency, but may be helpful for the early detection of LC.

Effects of Interaction Between Gestational Hypertension and History of Preterm Birth on the Risk of Preterm Birth: An Analysis Based on the National Vital Statistics System Database.

BACKGROUND Premature birth is an unsolved social and public problem. We aimed to explore the independent association and interaction effect between gestational hypertension (GH) and the history of preterm birth (HPB) on the risk of preterm birth. MATERIAL AND METHODS A case-control study involving participants with complete birth data was conducted using the United States National Vital Statistics System in 2019. Logistic regression analysis of 3 models were performed with odds ratio (OR) and 95% confidence interval (CI). Relative excess risk of interaction (RERI), attributable proportion of interaction (AP), and synergy index (S) were used to evaluate the interaction between GH and HPB on the risk of preterm birth. RESULTS A total of 2 822 624 participants were examined, with 10.83% in the known preterm birth group and 89.17% in the control group. Following adjustments for covariates, the association between GH and HPB and preterm birth was significant with ORs of 2.604 (95% CI: 2.573-2.635) and 3.047 (95% CI: 2.997-3.097), respectively. Moreover, there was a significant interaction between GH and HPB on preterm birth risk, with an OR of 6.095 (95% CI: 5.847-6.352), RERI of 1.222 (95% CI: 0.965-1.479), AP of 0.201 (95% CI: 0.167-0.235), and S of 1.317 (95% CI: 1.250-1.387), especially in participants with maternal age 20 to 29, 30 to 34, ≥35 years, and single birth. CONCLUSIONS GH and HPB might be positively associated with preterm birth, and there was an additive interaction between GH and HPB on preterm birth, indicating that obstetricians should pay more attention to prevention in this population.

Corrigendum: Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

[This corrects the article DOI: 10.3389/fonc.2021.766939.].

TRPV1 mediates itch-associated scratching and skin barrier dysfunction in DNFB-induced atopic dermatitis mice.

In chronic pruritic diseases such as atopic dermatitis (AD), pruritus and skin lesions are exacerbated by scratching in clinical and experimental settings. TRPV1 is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in itch-associated scratching in AD is poorly understood. In this study, we examined the efficacy of cutting off nails and TRPV1 antagonist, ruthenium red (RR) in a murine model of AD induced by DNFB and further investigated the underlying mechanism. Nail clipping or RR could markedly ameliorate the general AD-like symptoms as manifested by the reduced clinical severity of dermatitis, IgE and Th2-related cytokine levels, and mast cell degranulation. Moreover, scratching behaviour, the levels of pruritogenic mediators, including HIS, TSLP, IL-31 and SP, and skin pH and TEWL were all significantly decreased in nail clipping or RR-treated mice, suggesting a reduction in itch-associated scratching and skin barrier defects. Immunofluorescence staining and Western blot results revealed that antipruritic effect of nail clipping or RR in AD may be explained, at least in part, by the suppression of TRPV1 activation. In summary, these data show that TRPV1 mediates itch-associated scratching and subsequent skin barrier defects, suggesting its potential as a therapeutic target in AD.

A risk prediction model for selecting high-risk population for computed tomography lung cancer screening in China.

OBJECTIVE: Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer. MATERIALS AND METHODS: Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively. RESULTS: By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. CONCLUSIONS: We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

Comparative Studies on Hydraulic Fracturing Fluids for High-Temperature and High-Salt Oil Reservoirs: Synthetic Polymer versus Guar Gum.

The increasing energy demand has prompted engineers to explore deeper wells where rich oil and gas reserves exist. However, the high-temperature and high-salt conditions have impeded the further application of traditional water-based fracturing fluids in such reservoirs. Therefore, it is urgent to develop fracturing fluids that are suitable for such geographic characteristics. In this study, for the first time, a novel synthetic polymer, poly-(acrylamide-co-acrylic acid-co-2-acrylamido-2-methyl-1-propanesulfonic acid) (P3A), was investigated as a rheological modifier for water-based fracturing fluids in high-temperature and high-salt conditions and compared with a guar gum system. Results showed that the apparent viscosity increased with increasing P3A and guar gum concentrations, and the thickening ability of P3A was much better than that of guar gum. Despite the better shear and temperature resistance and proppant suspension ability of guar gum fluids in high-temperature and saturated salt conditions, plentiful solid residues after gel-breaking have prevented their progress in the petroleum industry. P3A fluids have no residues, but the unsatisfying proppant suspension capability and high dosage encourage us to promote their rheological performance via interaction with an organic zirconium crosslinker. Infrared spectroscopy and scanning electron microscopy were applied to guarantee the successful reaction of P3A with the crosslinker. The subsequent investigation indicated that the transformed fracturing fluid exhibited remarkably improved thickening capability and satisfying rheological performance in terms of temperature and shear resistance and proppant-carrying ability as well as gel-breaking results in a high-temperature and saturated salt environment. All of the above results suggest the potential application of crosslinked P3A in hydraulic fracturing for the reservoirs with hostile conditions, and this article also provides a new orientation for synthetic polymers utilized in the oil and gas industry.

Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

BACKGROUND: About 15% of lung cancers in men and 53% in women are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in non-smokers in China. METHODS: A large-sample size, population-based study was conducted under the framework of the Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. RESULTS: A total of 214,764 eligible subjects were included, with a mean age of 55.19 years. Subjects were randomly divided into the training (107,382) and validation (107,382) sets. Elder age, being male, a low education level, family history of lung cancer, history of tuberculosis, and without a history of hyperlipidemia were the independent risk factors for lung cancer. Using these six variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.753, 0.752, and 0.755 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a moderate predictive discrimination, with the AUC was 0.668, 0.678, and 0.685 for the 1-, 3- and 5-year lung cancer risk. CONCLUSIONS: We developed and validated a simple and non-invasive lung cancer risk model in non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in non-smokers.

Selection of high-risk individuals for esophageal cancer screening: A prediction model of esophageal squamous cell carcinoma based on a multicenter screening cohort in rural China.

The mortality benefit of esophageal squamous cell carcinoma (ESCC) screening has been reported in several studies; however, the results of ESCC screening programs in China are suboptimal. Our study aimed to develop an ESCC risk prediction model to identify high-risk individuals for population-based esophageal cancer screening. In total, 86 745 participants enrolled in a population-based esophageal cancer screening program in rural China between 2007 and 2012 were included in the present study and followed up until December 31, 2015. Models for identifying individuals at risk of ESCC within 3 years were created using logistic regressions. The area under the receiver operating curve (AUC) was determined to estimate the model's overall performance. A total of 298 individuals were diagnosed with ESCC within 3 years after baseline. The model of ESCC included the predictors of age, sex, family history of upper gastrointestinal cancer, smoking status, alarming symptoms of retrosternal pain, back pain or neck pain, consumption of salted food and fresh fruits and disease history of peptic ulcer or esophagitis (AUC of 0.81; 95% confidence interval: 0.78-0.83). Compared to the current prescreening strategy in our program, the cut-off value of 10 in the score-based model could result in 3.11% fewer individuals subjected to endoscopies and present higher sensitivity, slightly higher specificity and lower number needed to screen. This score-based risk prediction model of ESCC based on eight epidemiological risk factors could increase the efficiency of the esophageal cancer screening program in rural China.

An initial screening strategy based on epidemiologic information in esophageal cancer screening: a prospective evaluation in a community-based cancer screening cohort in rural China.

BACKGROUND AND AIMS: In China, regional organized esophageal cancer screening programs have been implemented since 2005. However, the implementation of these screening programs is still facing some urgent challenges, especially concerning identifying high-risk individuals. This study aimed to evaluate the risk stratification potential of the current initial assessment strategy used in a mass esophageal squamous cell carcinoma (ESCC) screening program in China. METHODS: A total of 43,875 participants without a previous cancer history enrolled in a mass ESCC screening program in China from 2007 to 2010 who had initial assessment results were included in this study and were followed until December 31, 2015. Eight potential risk factors for ESCC were evaluated in the initial assessment strategy. A comprehensive evaluation of the association of the initial assessment results with ESCC risk was performed by propensity score matching and Cox regression analysis. RESULTS: During a median follow-up of 5.5 years, 272 individuals developed ESCC. The high-risk population assessed at baseline had a higher risk of ESCC than the non-high-risk population, with a hazard ratio (HR) of 3.11 (95% confidence interval (CI), 2.33-4.14) after adjustment for sex, age, education level, income level, and body mass index. In addition, the initial assessment results of the high-risk population were significantly associated with the risk of all esophageal cancers (HR, 3.30; 95% CI, 2.51-4.33) and upper gastrointestinal cancers (HR, 3.03; 95% CI, 2.43-3.76). CONCLUSIONS: The initial screening tool in a mass ESCC screening program in China, consisting of 8 accessible variables in epidemiologic surveys, could be helpful for the selection of asymptomatic individuals for priority ESCC screening.

Topical application with conjugated linoleic acid ameliorates 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like lesions in BALB/c mice.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4-dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD-like skin lesions, scratching behaviour and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2-related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier-related protein, filaggrin (FLG). In addition, topical CLA significantly dose-dependently inhibited pro-inflammatory cytokines including interleukin (IL)-6, IL-1ß, tumour necrosis factor (TNF)-α and pro-inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in inflamed mice skin. Its anti-inflammatory effect was associated with the inhibition of DNFB-stimulated IκBα and NF-κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.