Intratumoral and Peritumoral Edema Radiomics Based on Fat-Suppressed T2- Weighted Imaging for Preoperative Prediction of Triple-Negative Breast Cancer.

AIM: Our aim was to explore the feasibility of using radiomics data derived from intratumoral and peritumoral edema on fat-suppressed T2-weighted imaging (T2 FS) to distinguish triple-negative breast cancer (TNBC) from non-triple-negative breast cancer (non-TNBC). METHODS: This retrospective study enrolled 174 breast cancer patients. According to the MRI examination time, patients before 2021 were divided into training (n = 119) or internal test (n = 30) cohorts at a ratio of 8:2. Patients from 2022 were included in the external test cohort (n = 25). Four regions of interest for each lesion were defined: intratumoral regions, peritumoral edema regions, regions with a combination of intratumoral and peritumoral edema, and regions with a combination of intratumoral and 5-mm peritumoral. Four radiomic signatures were built using the least absolute shrinkage and selection operator (LASSO) method after selecting features. Furthermore, a radio mic-radiological model was constructed using a combination of intratumoral and peritumoral edema regions along with clinical-radiologic features. Area under the receiver operating characteristic curve (AUC) calculations, decision curve analysis, and calibration curve analysis were performed to assess the performance of each model. RESULTS: The radiomic-radiological model showed the highest AUC values of 0.906 (0.788-1.000) and 82.5 (0.622-0.947) in both the internal and external test sets, respectively. The radiology-radiomic model exhibited excellent predictive performance, as evidenced by the calibration curves and decision curve analysis. CONCLUSION: The ensemble model based on T2 FS-based radiomic features of intratumoral and peritumoral edema, along with radiological factors, performed better in distinguishing TNBC from non-TNBC than a single model. We explored the possibility of developing explainable models to support the clinical decision-making process.

The impact of the intensity of media use on potential tourists' risk perception and travel protective behavioral intentions in COVID-19.

Introduction: In light of the COVID-19 pandemic, there is an increased need for potential travelers to gather information about their trips to mitigate perceived risks. This study aims to understand the relationship between the intensity of media use (both new and traditional), epidemic risk perception, and tourism protection behavior intention among potential tourists. Methods: A total of 491 valid questionnaires were collected in Shanghai, China. Factor analysis, path analysis, and effect analysis were conducted using SPSS and AMOS to examine the impact of different media types on epidemic risk perception and tourism protection behavior. Results: The findings indicate a positive association between new media use intensity and epidemic risk perception, as well as an intention to adopt safety-conscious tourism behaviors. In contrast, traditional media usage is inversely associated with risk perception but has no significant influence on protective behavior. The results also highlight the role of demographic factors, such as age, education level, occupation, and income, in modulating the relationship between media usage and risk perception. Discussion: The contrasting effects of new and traditional media suggest the need for a tailored approach in epidemic communication strategies. Public health officials should leverage new media to enhance risk perception and safety-oriented behaviors, while recognizing the role of traditional media in managing lower risk perceptions and assuaging panic. The study emphasizes the importance of personalized messaging based on demographic disparities in media usage and perception. The mediating role of risk perception in shaping protective behaviors offers insights for promoting adherence to safety protocols. Conclusion: This study contributes to a comprehensive understanding of media influences during health crises, emphasizing the responsibility of media platforms in transmitting accurate information. The findings call for a nuanced approach to epidemic communication, considering the strengths and weaknesses of different media types. Segmented and personalized messaging strategies can cater to demographic variations in media usage and perception. Enhancing risk perception through tailored messaging can promote protective behaviors and effectively manage public sentiment during health crises.

Evaluating the performance of four assays for carrier screening of spinal muscular atrophy.

BACKGROUND AND AIMS: Spinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular condition caused by biallelic mutations in the survival of motor neuron 1 (SMN1) gene. A homozygous deletion of the SMN1 gene accounts for approximately 95-98% of SMA patients. A highly homologous gene survival motor neuron 2 (SMN2) can partially compensate for SMN1 deletion, and its copy number is associated with disease severity. Population-based carrier screening by simultaneous quantification of SMN1 and SMN2 copy numbers is the best method to prevent SMA. MATERIALS AND METHODS: In this study, a total of 516 samples were re-tested for the SMN1 copy number by using quantitative polymerase chain reaction (qPCR), multiplex ligation probe amplification (MLPA), droplet digital PCR (ddPCR), high-resolution melting (HRM) analysis, and PCR-based capillary electrophoresis (PCR/CE) simultaneously. Then, the performance of these methods was compared by using MLPA results as the reference. RESULTS: The results of qPCR, ddPCR, HRM, and PCR/CE in detecting heterozygous deletion of SMN1 exon 7 and the results of ddPCR, HRM, and PCR/CE in detecting ≥2 copies of SMN1 exon7 are totally consistent with those of MLPA. The sensitivity and specificity of qPCR for detection of 2 copies of SMN1 exon 7 were 99.7% and 98.8%, respectively. The sensitivity and specificity of qPCR for detection of >2 copies of SMN1 exon 7 were 96.3% and 99.8%, respectively. Compared with the MLPA results, the sensitivity and specificity of qPCR and HRM for detection of heterozygous deletion of SMN1 exon 8 were 100% and 100%, respectively. They were 99.4% and 100%, respectively for detection of 2 copies, and 100% and 100%, respectively for detection of >2 copies. The results of PCR/CE in detecting SMN1 exon 8 were consistent with those of MLPA. CONCLUSION: All these four methods show excellent performance in detecting heterozygous deletion of SMN1 exon 7. All PCR/CE results are totally concordant with those of MLPA. As the most cost-effective method, qPCR also shows high sensitivity and specificity in detecting SMN1. Taken together, our study provides useful information to select appropriate methods for SMA carrier screening.

Red Meat Consumption and Risk of Cardio-Cerebrovascular Disease in Chinese Older Adults.

Associations between red meat consumption and cardio-cerebrovascular diseases (CCVDs) are mostly studied in Western populations but not in Chinese or elderly. This prospective study investigated adults ≥65 years from the China Kadoorie Biobank (CKB). Associations between red meat consumption and CCVD, ischemic stroke/transient ischemic attack (TIA), CCVD mortality, and all-cause mortality were determined by Cox regression. A total of 59,980 participants were analyzed, 14,715 (24.53%) of whom ate red meat daily, 9,843 (16.41%) ate red meat 4-6 days/week, 23,472 (39.13%) ate red meat 1-3 days/week, and 11,950 (19.92%) ate red meat less than 1 day/week. Average amount of red meat usual consumption was 38 g/day. After adjustment, per 50 g/day higher red meat consumption at baseline was significantly associated with increased incident CCVD (aHR = 1.10) among high-income subjects (≥ 10,000 RMB) and urban residents (aHR = 1.12). Per 50 g/day higher baseline red meat consumption was significantly associated with increased ischemic stroke/TIA in urban residents (aHR = 1.08) but decreased risk in rural residents (aHR = 0.84). Higher baseline red meat consumption was associated with lower CCVD mortality in the poorest (aHR = 0.78) and rural residents (aHR = 0.72) and lower all-cause mortality in the poorest (aHR = 0.82) and rural residents (aHR = 0.80). In general, among older adults in China, higher red meat intake independently predicted increased CCVD among urban and high-income individuals but not poor ones. Higher red meat intake appears to be protective against mortality in rural and low-income subjects. Socioeconomic status is a crucial modifying factor on the association between red meat consumption and adverse cardiovascular outcomes in China.

Effects of organic zinc on production performance, meat quality, apparent nutrient digestibility and gut microbiota of broilers fed low-protein diets.

The high cost of feed and nitrogen pollution caused by high-protein diets have become major challenges restricting sustainable development in China's animal husbandry sector. Properly reducing protein levels and improving protein utilization in feed are effective approaches to solving this problem. To determine the optimal dose of methionine hydroxyl analogue chelated zinc (MHA-Zn) in broiler diets with a 1.5% reduction in crude protein (CP), a total of 216 1-day-old broilers were randomly assigned into 4 groups (each group consisted of 3 replications with 18 broilers per replicate), and growth and development indexes were assessed after 42 days. The broilers in control group were fed a basic diet, whereas those in the three test groups were fed diets with a 1.5% reduction in CP. The results showed no significant difference in the edible parts of broilers between low-protein (LP) diet group (90 mg/kg MHA-Zn) and normal diet group (p > 0.05), and adding 90 mg/kg MHA-Zn to LP diet significantly improved ileum morphology and apparent total tract digestibility (ATTD) of nutrient (p < 0.01; p < 0.05). A 16S rRNA sequencing analysis indicated that supplementing the LP diet with 90 mg/kg MHA-Zn was adequate for production performance of broilers and promoted beneficial bacteria in the cecum (Lactobacillus, Butyricoccus, Oscillospira, etc.) (p < 0.01). In summary, adding an optimal dose of organic zinc (90 mg/kg MHA-Zn) in low protein diets led to enhanced production performance of broilers and optimized cecum microbiota. Additionally, the reduction of crude protein consumption in broiler production proved to be a cost-effective measure, while also mitigated nitrogen pollutant emissions in the environment.

Effects of supplemental nutrients on ovarian development and oviposition in Conogethes punctiferalis (Lepidoptera: Crambidae).

Conogethes punctiferalis is a serious pest in China affecting a wide variety of field crops, fruits, and forest trees. Many insects require supplemental nutrients after emergence to compensate for insufficient nutrients at the larval stage. In this study, to better understand the determinants of C. punctiferalis survival and reproduction, the impact of supplemental nutrition was examined. In particular, the effects of 11 treatments (5% sucrose, 10% sucrose, 15% sucrose, 5% sophora honey, 10% sophora honey, 15% sophora honey, 5% wild honey, 10% wild honey, 15% wild honey, distilled water, and blank control) on adult longevity and oviposition were evaluated, with detailed morphological analyses of ovarian development in the 10% sucrose, distilled water, and blank control groups. Conogethes punctiferalis required supplementary nutrition after emergence. Supplementary nutrition improved fecundity (number of eggs laid) and longevity, and 10% sucrose water had the greatest effects. The preoviposition period and oviposition period of C. punctiferalis females were longer, and the numbers of eggs in female ovarian tubes and eggs laid by females were higher in the 10% sucrose water group than in other groups. Females supplemented with distilled water laid a small number of eggs. Without nutrient supplementation, females did not lay eggs. In conclusion, supplemental nutrition was beneficial for ovarian development in female moths, prolonging the oviposition period and lifespan, and was an important factor affecting population dynamics. These results lay a foundation for further analyses of the nutritional requirements for C. punctiferalis in the field and provide a reference for indoor population feeding.

Morphologic Characters of the Rostrum in Two Weevils, Eucryptorrhynchus scrobiculatus Motschulsky and E. brandti Harold (Coleoptera: Curculionidae: Cryptorrhychinae).

(1) Eucryptorrhynchus scrobiculatus and E. brandti (Coleoptera: Curculionidae: Cryptorrhychinae) are both pests of Ailanthus altissima, found in China. During ovipositing, gravid females of the two weevils need to excavate a cavity in the oviposition substrate with their rostrum, while their oviposition sites are different. (2) In this study, to explore the boring mechanism of E. scrobiculatus and E. brandti during ovipositing, the morphologic characters of the rostra of two weevils were studied in detail by scanning electron microscopy and micro-CT. (3) Their rostra appear similar, but the rostrum surface of E. scrobiculatus is rougher than that of E. brandti; their fine structures of rostrum and sensilla distribution are similar, but the sensilla twig basiconica 3 is distributed at the apex of labial palpus in E. brandti females, while not at the apex of labial palpus in E. scrobiculatus females; their rostra are hollow and their cuticle thickness is constantly changing, but the proportion of the whole rostrum tube cuticle in E. scrobiculatus is significantly larger than that of E. brandti. The above structural differences make E. scrobiculatus more conducive to oviposition in the soil and E. brandti more conducive to oviposition in the trunk of A. altissima. (4) Overall, this study not only plays an important role in exploring the excavating mechanism during the oviposition of the two weevils, but also provides new insights into the coexistence of two weevil species on the same host A. altissima.

Cross-Domain Active Learning for Electronic Nose Drift Compensation.

The problem of drift in the electronic nose (E-nose) is an important factor in the distortion of data. The existing active learning methods do not take into account the misalignment of the data feature distribution between different domains due to drift when selecting samples. For this, we proposed a cross-domain active learning (CDAL) method based on the Hellinger distance (HD) and maximum mean difference (MMD). In this framework, we weighted the HD with the MMD as a criterion for sample selection, which can reflect as much drift information as possible with as few labeled samples as possible. Overall, the CDAL framework has the following advantages: (1) CDAL combines active learning and domain adaptation to better assess the interdomain distribution differences and the amount of information contained in the selected samples. (2) The introduction of a Gaussian kernel function mapping aligns the data distribution between domains as closely as possible. (3) The combination of active learning and domain adaptation can significantly suppress the effects of time drift caused by sensor ageing, thus improving the detection accuracy of the electronic nose system for data collected at different times. The results showed that the proposed CDAL method has a better drift compensation effect compared with several recent methodological frameworks.

Effect of season on slaughter performance, meat quality, muscle amino acid and fatty acid composition, and metabolism of pheasants (Phasianus colchicus).

This study aimed to investigate the effect of summer and winter on slaughter performance, muscle quality, flavor-related substance content, and gene expression levels related to the fat metabolism of pheasants. One-hundred 1-day-old pheasants were fed for 5 months starting in March and July and then, respectively, slaughtered in summer (August) and winter (December). The results revealed that compared with summer, winter not only increased pheasant live weight, dressed percentage, full-eviscerated yield, and muscle yield (p < 0.05) but also enhanced the activities of SOD and CAT in serum (p < 0.05). Winter significantly increased meat color, the contents of inosinic acid, and flavor amino acid in muscle. Amino acid contents in leg muscles of pheasants in winter were significantly higher than in summer except for histidine (p < 0.05). Winter increased the contents of muscle mono-unsaturated fatty acid, reducing saturated fatty acid. Summer improved fat synthesis in liver, promoted the deposition of triglycerides and cholesterol, and reduced the expression levels of fat metabolism-related genes in muscle, while winter increased the expression levels of genes related to muscle fat metabolism to provide energy for body and affect muscle fatty acid profile. Overall, pheasants fed in winter had better sensory quality and flavor than summer.

The Effect of Aspirin on the Primary Prevention of Major Adverse Cardiac and Cerebrovascular Events in Chinese Older Adults: A Registration Study.

BACKGROUND: Low-dose acetylsalicylic acid (aspirin) prevents stroke and myocardial infarction in patients with cardiovascular disease (CVD), but whether it should be used for primary CVD prevention in older Chinese adults remains unclear. METHODS: This prospective study investigated Chinese people aged > 70 years participating in the Kadoorie Study of Chronic Disease. The subjects were grouped as aspirin users and nonusers. Propensity score matching (PSM) was used to achieve balanced baseline characteristics. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE). The secondary outcomes were all-cause mortality, cardiovascular and/or cerebrovascular disease (CCVD) mortality, and bleeding events. Survival curves were used to compare the outcomes between groups. Cox regression was used to identify the risk factors for the outcomes. RESULTS: In total, 4791 participants were categorized as aspirin users (n = 257) or nonusers (n = 4534). PSM resulted in 252 and 951 participants in the aspirin user and nonuser groups, respectively. Median follow-up was 8.6 years. Aspirin did not influence MACCE, all-cause mortality, or bleeding events, but it did influence CCVD deaths (p = 0.019). Male sex (hazard ratio [HR] 1.652; 95% confidence interval [CI] 1.217-2.243; p = 0.001), body mass index (BMI) (HR 1.053; 95% CI 1.008-1.100; p = 0.021), and systolic blood pressure (HR 1.009; 95% CI 1.003-1.016; p = 0.004) were independent risk factors for MACCE. Survival analysis showed higher rates of CCVD mortality among aspirin users (HR 1.363; 95% CI 1.040-1.786; p = 0.025), but this was not significant in the regression analysis. CONCLUSIONS: There were no significant benefits from using aspirin as primary prevention for MACCE in older Chinese adults.

Prognostic value of CAD-RADS classification by coronary CTA in patients with suspected CAD.

BACKGROUND: The study sought to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) classification with traditional coronary artery disease (CAD) classifications and Duke Prognostic CAD Index for predicting the risk of all-cause mortality in patients with suspected CAD. METHODS: 9625 consecutive suspected CAD patients were assessed by coronary CTA for CAD-RADS classification, traditional CAD classifications and Duke Prognostic CAD Index. Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality. Discriminatory ability of classifications was assessed using time dependent receiver-operating characteristic (ROC) curves and The Hosmer-Lemeshow goodness-of-fit test was employed to evaluate calibration. RESULTS: A total of 540 patients died from all causes with a median follow-up of 4.3 ± 2.1 years. Kaplan-Meier survival curves showed the cumulative events increased significantly associated with CAD-RADS, three traditional CAD classifications and Duke Prognostic CAD Index. In multivariate Cox regressions, the risk for the all-cause death increased from HR 0.861 (95% CI 0.420-1.764) for CAD-RADS 1 to HR 2.761 (95% CI 1.961-3.887) for CAD-RADS 4B&5, using CAD-RADS 0 as the reference group. The relative HRs for all-cause death increased proportionally with the grades of the three traditional CAD classifications and Duke Prognostic CAD Index. The area under the time dependent ROC curve for prediction of all-cause death was 0.7917, 0.7805, 0.7991for CAD-RADS in 1 year, 3 year, 5 year, respectively, which was non-inferior to the traditional CAD classifications and Duke Prognostic CAD Index. CONCLUSIONS: The CAD-RADS classification provided important prognostic information for patients with suspected CAD with noninvasive evaluation, which was non-inferior than Duke Prognostic CAD Index and traditional stenosis-based grading schemes in prognostic value of all-cause mortality. Traditional and simplest CAD classification should be preferable, given the more number of groups and complexity of CAD-RADS and Duke prognostic index, without using more time consuming classification.

Serum miR-27a is a biomarker for the prognosis of non-small cell lung cancer patients receiving chemotherapy.

BACKGROUND: Lung cancer has a high incidence and a 5-year survival rate of less than 15%. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Chemotherapy and immunotherapy are the most frequently used alternative treatments for patients with advanced-stage NSCLC in whom surgery failed. Previous studies have suggested that miR-27a is involved in cancer development and progression. The purpose of this study was to investigate the clinical value of miR-27a in the prognosis of NSCLC patients after chemotherapy. METHODS: Flow cytometry was used to detect the apoptosis rate of SPC-A1 cells treated with optical cisplatin at different times. Simultaneously, the expression of miR-27a in supernatants and cells was detected. Fifty-two newly diagnosed NSCLC patients were recruited. All patients received gemcitabine and cisplatin as first-line chemotherapy and docetaxel as second-line chemotherapy. At the end of every chemotherapy cycle, a therapeutic evaluation was performed according to the RECIST criteria. The expression of serum miR-27a was detected in each cycle. RESULTS: After treatment with 2.5 µg/mL cisplatin, the apoptosis rates of SPC-A1 cells were significantly greater than those of the paired untreated control groups at 12, 24, 48 and 72 h. The expression of miR-27a in supernatants and cells was also consistent with the apoptosis rate and changed a time-dependent manner. The chi-square test showed that an increase in miR-27a after chemotherapy was more common in patients who achieved partial response (PR) than in those who achieved no response (NR) (61.5% vs. 30.8%, P=0.026). Kaplan-Meier survival analysis indicated that patients with decreased miR-27a levels had poorer outcomes than those with increased miR-27a levels (P<0.05). Furthermore, dynamic changes in serum miR-27a with a gradual increasing trend during chemotherapy predicted a good prognosis. CONCLUSIONS: Collectively, our results suggest that miR-27a is involved in the apoptosis of lung cancer cells and that serum miR-27a levels are related to the prognosis of NSCLC patients. The expression levels of miR-27a in the serum may be an independent predictor for the prognosis of NSCLC.

Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia.

OBJECTIVE: To study chest CT images and clinical characteristics of COVID-19 pneumonia in pregnant patients to examine any correlation. METHODS: Between December 31, 2019 and March 7, 2020, 23 hospitalized pregnant patients with confirmed COVID-19 were enrolled in the study. Clinical presentations were collected retrospectively from records, including laboratory testing, chest CT imaging, and symptoms. Descriptive analysis and correlation of patients' clinical and CT characteristics were performed. Laboratory results from time of first admission and CT absorption (defined as reduction in lesion area, decrease in density, and absorption of some solid components) were compared between symptomatic and asymptomatic patients. RESULTS: Fifteen (65.2%) patients were asymptomatic with patchy ground-glass opacity in a single lung lobe. Eight (34.8%) patients were symptomatic with multiple patchy ground-glass shadows, consolidation, and fibrous stripes. Differences in lymphocyte percentage and neutrophil granulocyte rate between first admission and CT absorption were significant (P<0.001). Median absorption time was shorter in the asymptomatic group compared with the symptomatic group (5 vs 10 days; P<0.001). Median hospitalization time between asymptomatic and symptomatic patients was 14 vs 25.5 days; P>0.001. Median absorption time and length of hospitalization for all patients was 6 days (IQR 5-8) and 17 days (IQR 13-25), respectively. CONCLUSION: Radiological findings and clinical characteristics in pregnant women with COVID-19 were similar to those of non-pregnant women with COVID-19. Median absorption time and length of hospitalization in asymptomatic patients were significantly shorter than in symptomatic patients. Lymphocyte percentage and neutrophil granulocyte rate may be used as laboratory indicators of CT absorption.

Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia.

The coronavirus disease 2019 (COVID-19) pneumonia is a recent outbreak in mainland China and has rapidly spread to multiple countries worldwide. Pulmonary parenchymal opacities are often observed during chest radiography. Currently, few cases have reported the complications of severe COVID-19 pneumonia. We report a case where serial follow-up chest computed tomography revealed progression of pulmonary lesions into confluent bilateral consolidation with lower lung predominance, thereby confirming COVID-19 pneumonia. Furthermore, complications such as mediastinal emphysema, giant bulla, and pneumothorax were also observed during the course of the disease.

[Effects of different grasses cultivation on apple orchard soil microbial community]. / 不同生草处理对苹果园土壤微生物群落的影响.

Taking naturally growing grass (NG) as comparison, high-throughput sequencing technique was adopted to examine the effects of Lolium perenne (LP), Trifolium repens (TR), Vulpia myuros (VM), and Vicia villosa (VV) cultivation on soil microbial community in apple orchard of Yanggu County, Shandong Province, and the correlations of soil microbial community with soil nutrient and physicochemical property. The results showed that LP increased the relative abundance of Alternaria and Aspergillus in soil, TR increased that of Gibberella, VM increased Aureobasidium and Chaetomium, and VV increased probiotics such as Nitrososophaera and Metarhizium. However, the quantity of pathogenic bacteria Ralstonia was improved in NG treatment. Results from Spearman correlation analysis showed that the abundance of Bacillus was significantly positively correlated with the concentration of soil organic matter. The abundance of Aspergillus was significantly negatively correlated with available phosphorus, available potassium, CEC, and organic matter. The abundance of Metarhizium was significantly positively correlated with soil pH and CEC. Planting VV between rows of apple orchards, and enhancing the soil organic matter and nutrients content in a certain extent, helped to improve soil micro-ecological environment.

Noninvasive prenatal diagnosis for X-linked disease by maternal plasma sequencing in a family of Hemophilia B.

OBJECTIVE: To apply a Hidden Markov Model to test Hemophilia B in a fetus by maternal plasma sequencing only employing proband and maternal haplotypes. CASE REPORT: A family at risk for Hemophilia B was recruited in this study. We performed genetic diagnosis on the proband using our targeted capture system (containing F9 gene coding region, highly heterozygous SNPs and a 13-kb chromosome Y specific region), and revealed a causative F9 gene mutation (c.190T>C, p.Cys64Arg). Maternal plasma cell-free DNA obtained at 8 weeks of gestation was targeted-captured and sequenced using the customized system. The fetus inherited the F9 (c.190T>C, p.Cys64Arg) mutation according to the Hidden Markov Model. The mother continued the pregnancy. CONCLUSIONS: This study is the first report of a haplotype-based approach in NIPD of Hemophilia B. With further evaluation, this method might be useful for NIPD of Hemophilia B and for other X-linked single-gene disorders.

Changes in regulatory T cells in patients with ovarian cancer undergoing surgery: Preliminary results.

Regulatory T cells (Treg) suppress immune responses in patients with cancer. Surgery is the most effective therapeutic strategy for ovarian cancer (OC). However, the interplay between the Treg population and surgical resection remains unclear. 61 patients with OC who received no prior treatment were enrolled in the study. Treg percentages were characterized from peripheral blood mononuclear cells. We investigated CD4+CD25+, CD4+CD25+Foxp3+, CD8+CD28-, and CD8+Foxp3+ Tregs in OC patients and their postoperative changes using flow cytometry. Treg percentages were significantly higher in OC patients than those in benign ovarian tumors (BOT) and healthy controls. Higher percentages of Tregs were found in patients with stage III/IV than stage I/II OC. Treg percentages were significantly decreased postoperatively. The postoperative Treg percentages in patients with stage I/II OC were similar to those in BOT patients, while postoperative Treg percentages in patients with stage III/IV OC remained higher. Tregs were markedly lower on postoperative day (POD) 3 than preoperatively. They increased slightly after 7days, but remained lower than preoperative levels. These data suggested that Tregs continued to decline from POD 7 to POD 30. Treg percentages are correlated with the tumor burden and could be a key factor in monitoring the immunological status of patients with OC.

MiRNA-145 suppresses lung adenocarcinoma cell invasion and migration by targeting N-cadherin.

OBJECTIVE: To investigate the roles of miR-145 in lung adenocarcinoma (LAC) and to clarify the regulation of N-cadherin by miR-145. RESULTS: In 57 paired clinical LAC tissues, diminished miR-145 was significantly correlated with the lymph node metastasis and was negatively correlated with N-cadherin mRNA level expression. Wound healing and transwell assays revealed a reduced capability of tumor metastasis induced by miR-145 in LAC. miR-145 negatively regulated the invasion of cell lines through targeting N-cadherin by directly binding to its 3'-untranslated region. Silencing of N-cadherin inhibited invasion and migration of LAC cell lines similar to miR-145 overexpression. CONCLUSIONS: MiR-145 could inhibit invasion and migration of lung adenocarcinoma cell lines by directly targeting N-cadherin.

Gene expression profiling of CD8+ T cells induced by ovarian cancer cells suggests a possible mechanism for CD8+ Treg cell production.

OBJECTIVES: The aim of this study was to investigate a possible mechanism of CD8+ regulatory T-cell (Treg) production in an ovarian cancer (OC) microenvironment. MATERIALS AND METHODS: Agilent microarray was used to detect changes in gene expression between CD8+ T cells cultured with and without the SKOV3 ovarian adenocarcinoma cell line. QRT-PCR was performed to determine glycolysis gene expression in CD8+ T cells from a transwell culturing system and OC patients. We also detected protein levels of glycolysis-related genes using Western blot analysis. RESULTS: Comparing gene expression profiles revealed significant differences in expression levels of 1420 genes, of which 246 were up-regulated and 1174 were down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that biological processes altered in CD8+ Treg are particularly associated with energy metabolism. CD8+ Treg cells induced by co-culture with SKOV3 had lower glycolysis gene expression compared to CD8+ T cells cultured alone. Glycolysis gene expression was also decreased in the CD8+ T cells of OC patients. CONCLUSIONS: These findings provide a comprehensive bioinformatics analysis of DEGs in CD8+ T cells cultured with and without SKOV3 and suggests that metabolic processes may be a possible mechanism for CD8+ Treg induction.

TGF-ß1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment.

CD8+ regulatory T cells (Tregs) contribute to cancer progression and immune evasion. We previously reported that CD8+ Tregs could be induced in vitro by co-culture of CD8+ T cells with the OC cell lines SKOV3/A2780. Here, we described the role of TGF-ß1 in CD8+ Treg induction by the OC microenvironment. OC patients expressed high levels of TGF-ß1, as did the co-culture supernatant from CD8+ T cells and SKOV3. Additionally, TGF-ß1 levels were positively correlated with CD8+ Treg percentages in OC. Neutralization experiments, cytokine studies and proliferation assays revealed that the in vitro-induced CD8+Tregs depended at least partially on up-regulated expression of TGF-ß1 to exert their suppressive function. CD8+ T cells cultured with SKOV3 exhibited marked activation of p38 MAPK than CD8+ T cells cultured alone, which could be inhibited by TGF-ß1-neutralizing antibody. Moreover, the p38 specific inhibitor SB203580 dose-dependently blocked the TGF-ß1 activated conversion of CD8+ T cells into CD8+ Tregs. These data suggested that in vitro-induction of CD8+ Tregs depended in part on TGF-ß1 activation of p38 MAPK signaling. Therefore, p38 MAPK could be a therapeutic target in OC anti-tumor immunotherapy.