Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma

Objective Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC. Methods Immunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers. Results LOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different. Conclusion This study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC (AU)

Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC. METHODS: Immunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers. RESULTS: LOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different. CONCLUSION: This study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC.

Variations of trophic structure and niche space in fish community along a highly regulated subtropical large river.

The trophic interactions between consumers and resources play a vital role in the stability of communities. In river systems, fragmentation of natural habitats and environmental changes alters the energy basis and community composition, consequently leading to variations in the community's trophic structure and niche space. However, our understanding of how the trophic structure responds to environmental changes is still very limited. Here, based on stable isotope data, we explored and compared trophic positions (TPs), community-wide trophic metrics, and isotope niche space of fish communities in three reaches with different hydrogeomorphic conditions along a highly regulated subtropical river over three seasons. The community trophic structure and niche space showed notable spatiotemporal variations. Overall, the downstream reach had lower TPs, trophic diversity but higher trophic redundancy. The middle reach occupied a wider isotope niche space than other reaches, with the largest niche size during autumn. Furthermore, the niche overlap was relatively high in winter between reaches and in the downstream between seasons. The results implied a homogenization of feeding functional groups and energy flow pathways of species in the downstream community associated with the change of energy source and stability of hydrological conditions. The relationship between trophic structure and environmental factors suggested that the dam-induced alteration in hydrological-related aspects may drive the changes in the functional group composition, together with changes in energy basis, resulting in differences in the trophic structure of the community. The results of the present study deepen our understanding of how ecosystem functions respond to disturbance, thus contributing to improved ability to conserve river ecosystems.

Compare the Efficacy and Safety of Modified Combined Short and Long Axis Method versus Oblique Axis Method for Right Internal Jugular Vein Catheterization in Adult Patients (The MCSLOA Trial): Study Protocol of a Randomized Controlled Trial.

Background: Ultrasound-guided internal jugular vein (IJV) catheterization has become a standard procedure as it yields a higher success rate and fewer mechanical complications compared with an anatomical landmark technique. There are several common methods for ultrasound guidance IJV catheterization, such as short-axis out-of-plane, long-axis in-plane and oblique axis in-plane, but these technologies are still developing. It is important to further study the application of different ultrasound-guided IJV puncture techniques and find an effective and safe ultrasound-guided puncture technique. Methods: A China randomized, open-label, parallel, single center, positive-controlled, non-inferiority clinical trial will evaluate 190 adult patients undergoing elective surgery and need right jugular vein catheterization. Study participants randomized in a 1:1 ratio into control and experimental groups. The control group will take the oblique axis in-plane method for IJV catheterization. The experimental group will take the Modified combined short and long axis method. The primary endpoint of the trial is the rate of one-time successful guidewire insertion without posterior wall puncture (PWP). Secondary endpoints are the number of needle insertion attempts, the total success rate, the procedure time, and mechanical complications. Conclusion: This randomized controlled trial will evaluate the effectiveness and safety of Modified combined short and long axis method and oblique axis in-plane method for right IJV catheterization in adult patients.

Air-polluted environmental heavy metal exposure increase lung cancer incidence and mortality: A population-based longitudinal cohort study.

BACKGROUND: An increased risk of lung cancer has been observed due to exposure to certain environmental heavy metals. This study elucidated the role of air-polluted heavy metals in the development of lung cancer. METHODS: A longitudinal cohort study involving the general population was conducted to compare heavy metal content among lung cancer patients. The urine concentrations of heavy metals were measured. Questionnaire surveys were designed to collect exposure-related demographic and lifestyle data of the study subjects. RESULTS: Participants residing near the petrochemical industrial area with higher air Cd concentration had relatively higher urinary concentration of Cd. After adjusting for sociodemographic and behavioral factors, tobacco smoking and air pollution remained as potential sources of Cd exposure. An increased prevalence of lung cancer was observed in the highly polluted zone. The risk of lung cancer incidence increased 1.25-fold for each 1 µg/g-creatinine increase in urine Cd level. Patients with lung cancer had significantly higher urinary Cd concentrations. Lung cancer patients with higher urinary Cd level had significantly poor survival (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine; survival, medium, 192.0 vs 342.5 days, p < 0.001). At the longitudinal follow-up, participants with higher urinary Cd level had a higher risk of lung cancer incidence (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine: 3.91% v.s. 0.87%, hazard ratio: 4.65, p < 0.001). CONCLUSIONS: Accumulation of Cd could be a risk of lung cancer occurrence. High exposure to Cd may result in poor prognosis in lung cancer patients.

[Analysis of the Status of Depression and the Influencing Factors in Middle-Aged and Older Adults in China].

OBJECTIVE: To understand the status of depression and its influencing factors in the middle-aged and older adult populations aged 45 and above in China on the basis of data from the 2018 China Family Panel Studies (CFPS), and to provide empirical evidence for the improvement of the mental health of the middle-aged and older adults and the alleviation of their depressive symptoms. METHODS: The source of the research data was the 2018 CFPS. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depression. A two-level two-category unconditional logistics regression method was used to analyze the influencing factors of the prevalence of depressive symptoms. RESULTS: The 80th percentile interval score of depression score was used as the critical value, and the detection rate of depressive symptoms was 23.61%. It was more likely for women to suffer from depressive symptoms than it was for men. Widowed individuals were at an even higher risk for having depression. The more education one had, the lower the possibility of developing depression. Middle-aged and older adults in rural areas were more likely to suffer from depression. Middle-aged and older adults with chronic diseases and self-rated poor health were at higher risk of depression. Sleep time is a protective factor that suppressed symptoms. After controlling the above-mentioned individual-level factors, middle-aged and older adults in coastal and economically developed areas were less likely to suffer from depression than those from inland and economically underdeveloped areas did. CONCLUSION: The health departments concerned should focus on the depressive symptoms of women, widowed individuals, and middle-aged and older adults with chronic diseases. In rural areas and underdeveloped inland regions, the state should invest more health resources in the prevention and improvement of depression among middle-aged and older adults.

[Influence of Social Capital on the Life Quality of Patients with Chronic Diseases-A Study Based on EQ-5D-5L Scale].

OBJECTIVE: To explore the influence of social capital on the quality of life of patients with chronic non-communicable diseases. METHODS: A multi-phase stratified cluster sampling method was adopted to select the survey respondents. Professionally trained surveyors made home visits in order to conduct face-to-face questionnaire surveys in person. European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) and a self-developed social capital scale were used to investigate the quality of life and social capital of the respondents. Factor analysis and Cronbach's α coefficient test were done to verify the reliability and validity of the self-developed social capital scale. The χ 2 test and robust Tobit regression model were used to analyze the impact of social capital on the quality of life of patients with chronic non-communicable diseases. RESULTS: The self-developed social capital scale showed excellent performance. The Cronbach's α coefficient was 0.728, the KMO value was 0.716, and the result of Bartlett's test of sphericity was statistically significant ( P<0.001), indicating that the data were well suited for factor analysis. The four common factors cumulatively explained 68.27% of the total variation. The health utility value of the survey respondents was 0.869±0.181. Those who could walk around, shower and dress themselves, and perform usual activities without any problem accounted for 75.70%, 80.10%, and 74.1% of the respondents, respectively. Those who had pain or discomfort and anxiety or depression, with no self-perceived problem were 43.40% and 58.90%, respectively. In the EQ-5D-5L scale, the self-rated health influencing factors of the physical health dimension were community safety and interpersonal network relationships. The influencing factors of social function health was community safety and mental health was affected by community safety, community trust and interpersonal network relationships. When community safety improved by one level, the health utility value of patients with chronic non-communicable diseases increased by 0.046, and when interpersonal network relationships improved by an additional level, their health utility value increased by 0.037. CONCLUSION: The main problem of the quality of life of patients with chronic non-communicable diseases was found in the mental health dimension. In the process of treating chronic non-communicable diseases, attention should also be given to psychological counseling. Community safety and interpersonal network relationships are the protective factors for self-rated health status. Providing a safe community environment and expanding interpersonal networks help improve the health of patients.

Comprehensive methylation profile of CSF cfDNA revealed pathogenesis and diagnostic markers for early-onset Parkinson's disease.

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.

Lay abstract Early-onset Parkinson's disease (EOPD), a progressive disease of the nervous system marked by tremor, muscular rigidity and slow and imprecise movement, is generally found in people under the age of 40 years. In this study, we performed methylation test on cerebrospinal fluid (CSF). The test showed that specific CSF methylation profiles could be used to help EOPD diagnosis. A subset of differentially methylated genes were also identified, which could also be used as markers for EOPD diagnosis. In future, we will validate the methylation test in blood and try to find blood-based diagnostic markers to facilitate the diagnosis of EOPD by a single blood draw.

Asymptomatic carbon dioxide embolism during transoral vestibular thyroidectomy: A case report.

BACKGROUND: Endoscopic thyroidectomy has obvious advantages over conventional surgical techniques in terms of postoperative cosmetic outcome. Although the incidence of carbon dioxide embolism (CDE) during endoscopic thyroidectomy is very low, it is potentially fatal. The clinical manifestations of CDE vary, and more attention should be paid to this disorder. CASE SUMMARY: A 27-year-old man was scheduled for thyroidectomy by the transoral vestibular approach. The patient had no other diseases or surgical history. During the operation, he developed a CDE following inadvertent injury of the anterior jugular vein. The clinical manifestation in this patient was a transient sharp rise in end-tidal carbon dioxide, and his remaining vital signs were stable. In addition, loud coarse systolic and diastolic murmurs were heard over the precordium. The patient was discharged on day 4 after surgery without complications. CONCLUSION: A transient sharp rise in end-tidal carbon dioxide is considered a helpful early sign of CDE during endoscopic thyroidectomy.

Esophageal superficial adenosquamous carcinoma resected by endoscopic submucosal dissection: A rare case report.

BACKGROUND: Adenosquamous carcinoma (ASC), which is comprised of squamous cell carcinoma (SCC) and adenocarcinoma elements, is a rare histological type of esophageal carcinoma. Few reports have focused on the endoscopic findings and the effectiveness of the endoscopic treatment of early ASC. CASE SUMMARY: A 77-year-old man underwent esophagogastroduodenoscopy for heartburn. A flat lesion with an uneven and slightly elevated central portion was found in the distal esophagus. Magnifying endoscopy with narrow-band imaging showed a well-demarcated brownish area with dendritically branched abnormal vessels and highly irregular intrapapillary capillary loops. A histopathological diagnosis of SCC was obtained by endoscopic biopsy. Endoscopic ultrasonography revealed a hypoechoic mass confined to the mucosa layer. The lesion was suspected to be SCC with invasion into the muscularis mucosa. The lesion was resected en bloc by endoscopic submucosal dissection and histologically diagnosed as esophageal ASC limited within the muscularis mucosa, which was completely resected without lymphovascular or neural invasion. The SCC element was the pre-dominant element. The adenocarcinoma element formed ductal and nested structures distributed in a focal pattern. The patient underwent only endoscopic submucosal dissection and has been under annual endoscopic and radiographic surveillance for 3 years without recurrence. CONCLUSION: For early ASC confined within the mucosal layer, complete endoscopic resection might also be a curative treatment.

Aspiration pneumonia during general anesthesia induction after esophagectomy: A case report.

BACKGROUND: Esophageal cancer is a common malignant tumor of the digestive system. At present, surgery is the most important treatment strategy. After esophagectomy and gastric esophagoplasty, the patients are prone to regurgitation. However, these patients currently do not receive much attention, especially from anesthesiologists. CASE SUMMARY: A 55-year-old woman was scheduled for right lower lung lobectomy. The patient had undergone radical surgery for esophageal cancer under general anesthesia 6 mo prior. Although the patient had fasted for > 17 h, unexpected aspiration still occurred during induction of general anesthesia. Throughout the operation, oxygen saturation was 98%-100%, but the airway pressure was high (35 cmH2O at double lung ventilation). The patient was sent to the intensive care unit after surgery. Bedside chest radiography was performed, which showed exudative lesions in both lungs compared with the preoperative image. After surgery, antibiotics were given to prevent lung infection. On day 2 in the intensive care unit, the patient was extubated and discharged on postoperative day 7 without complications related to aspiration pneumonia. CONCLUSION: After esophagectomy, patients are prone to regurgitation. We recommend nasogastric tube placement followed by rapid sequence induction or conscious intubation.

[Evaluation of Reliability and Validity of EQ-5D-5L Based on Residents in Southwest China].

OBJECTIVE: To explore the reliability and validity of the EQ-5D-5L scale in the population of southwest China. METHODS: The internal consistency reliability is measured by Cronbach's α coefficient and the structural validity is measured by factor analysis. The difference in health utility value of different characteristic populations is compared by t test and analysis of variance. RESULTS: Cronbach's α coefficient was 0.857. Exploratory factor analysis extracts two common factors whose cumulative contribution rate is 77.311%. The first common factor represents mobility, self-care and uaual activities. The second common factor represents pain/discomfort and anxiety/depression. The results of confirmatory factor analysis showed that the correlation of the two common factors was 0.659, the average variance of the first common factor was 0.862 and the combination reliability was 0.949, and the average variance extracted of the second common factor was 0.587 and the composite reliability was 0.739. The factor loadings for mobility, self-care and uaual activities on the first common factor were 0.871, 0.945 and 0.967, respectively. The loadings for pain/discomfort and anxiety/depression on the second common factor were 0.708 and 0.820, respectively. CONCLUSION: EQ-5D-5L has good reliability and validity when it is applied to the measurement of healthy life quality of residents in Southwest China.

HE4 as a biomarker for diagnosis of lung cancer: A meta-analysis.

BACKGROUND: The aim of our study was to assess the value of serum human epididymis protein 4 (HE4) to diagnose lung cancer and provide reliable scientific conclusions to guide clinical practice. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, and WANFANG databases was conducted to identify all studies examining serum HE4 in the diagnosis of lung cancer published up to June, 2017. The Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of each trial. The meta-analysis was performed using STATA software and Review Manager 5.3. RESULTS: There were 21 studies involving 1883 cases and 1696 controls included in our meta-analysis. The pooled sensitivity and specificity of HE4 for diagnosing lung cancer were 0.73 (95% confidence interval [CI] 0.68-0.78) and 0.86 (95% CI 0.81-0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.4 (95% CI 3.8-7.5) and 0.31 (95% CI 0.26-0.37), respectively. The diagnostic odds ratio was 17 (95% CI 12-26). The area under the curve of the summary receiver-operating characteristic curve was 0.86 (95% CI 0.83-0.89). Race, assay method, type of cancer, sample size, and publication date might be sources of heterogeneity in our meta-analysis. Subgroup analyses showed that the sensitivity in Caucasians was higher than that in Asians (0.81, 95% CI 0.71-0.91; and 0.71, 95% CI 0.66-0.77, respectively), but the specificity in Asians was better than that in Caucasians (0.87, 95% CI 0.81-0.92; and 0.85, 95% CI 0.73-0.97, respectively). The chemiluminescent microparticle immunoassay had the highest sensitivity, with 0.79 (95% CI 0.73-0.97), and the enzyme-linked immunosorbent assay had the highest specificity, with 0.87 (95% CI 0.79-0.94). HE4 had high diagnostic efficacy when screening for small cell lung cancer with the highest specificity (0.90, 95% CI 0.77-1.00). CONCLUSIONS: HE4 is a relatively promising and effective biomarker for the diagnosis of lung cancer. Furthermore, given the limitations of our study, additional large-scale and well-designed studies are needed in the future.

[The Effects of Social Capital on Depressive Symptoms of Elderly Patients with Chronic Diseases in Urbanized Communities].

OBJECTIVE: To understand the effects of social capital on depressive symptoms of elderly patients with chronic diseases in urbanized communities, and to explore preventive measures to promote their mental health. METHODS: A multi-stage stratified cluster sampling method was used to extract 740 elderly patients with chronic diseases in the urbanized communities in Chengdu and Kunming. The questionnaire survey was conducted by using the center of depression rating scale (CES-D) and the self-made social capital scale. Multivariate unconditional logistic regression was used to analyze the impact of urbanized residents' social capital on depressive symptoms. RESULTS: The self-made social capital scale has good reliability and validity. The incidence of depressive symptoms in this study was 24.9%. The incidence of depressive symptoms in elderly females with chronic diseases was higher (P < 0.05); the residents with high "sense of social trust and security" had lower risk of incidence of depressive symptoms 〔odds ratio (OR)=0.489〕; the residents with higher "community belonging" had a lower risk of incidence of depressive symptoms (OR=0.570), and the residents with higher "social support" scores had a lower risk of incidence of depressive symptoms (OR=0.233). CONCLUSION: Targeted measures should be taken to intervene in the social capital factors affecting the depressive symptoms of elderly patients with chronic diseases in urbanized communities to improve their mental health.

Intra-rectal use of epinephrine in radiotherapy of prostate cancer.

Purpose: The aim of the study was to evaluate the feasibility and toxicity of intra-rectal epinephrine during prostatic radiotherapy. Materials and methods: A total of 34 patients with prostate cancer were randomized to receive daily intra-rectal epinephrine (4 mg in 40 mL, n=16) or placebo (40 mL normal saline, n=18) 5 min before daily radiotherapy. Physical examination including systolic blood pressure (SBP) and heart rate (HR) was performed before, 5 min after, and 20 min after intra-rectal use. Toxicities were graded using the Radiation Therapy Oncology Group standard. A two-sided Fisher's exact test was used to compare proportions between groups. A mixed-effects model was used to analyze multiple measurements of SBP and HR. Survival curves were calculated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: All patients completed the protocol treatment and reported no cardiovascular symptoms after intra-rectal administration. There were no differences in SBP and HR between these two groups at any time point (before, 5 min after, and 20 min after epinephrine). At 5 weeks after the start of radiotherapy, the incidence of rectal toxicity≥grade 2 was 27.8% (5/18) for the control group versus 12.5% (2/16) for the epinephrine group, but was not statistically significant (p=0.4). There was no rectal toxicity≥grade 2 in these two groups beyond 2-year follow-up. The 5-year biochemical relapse-free survival was 75.0% and 72.2% for the epinephrine and control group, respectively. Conclusion: Results of this pilot randomized trial have demonstrated that intra-rectal administration of epinephrine is feasible and safe in prostatic radiotherapy. Its radio-protective effect warrants further investigation.

Perinatal polychlorinated biphenyls and polychlorinated dibenzofurans exposure are associated with DNA methylation changes lasting to early adulthood: Findings from Yucheng second generation.

Epigenome-wide DNA methylation has not been studied in men perinatally exposed to PCBs and dioxins. Therefore, we examined whether perinatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) induces sustained methylation changes lasting to early adulthood. We used the Illumina HumanMethylation450 BeadChip to assess DNA methylation in whole blood among Yucheng second generation (people perinatal exposed to high PCBs and PCDFs) compared with referents. Thirty male offspring from the Yucheng cohort were randomly selected and matched with 30 male offspring from the Yucheng' neighborhood referents with similar backgrounds. Methylation differences between the Yucheng second generation and non-exposed referents were identified using a P value < 1.06 × 10-7. Differential DNA methylation with epigenome-wide statistical significance was observed for 20 CpGs mapped to 11 genes, and 19 CpGs were correlated with gestational levels of PCBs or PCDF toxic equivalency (PCDF-TEQ) with the same direction of effect. Among the 11 genes, AHRR and CYP1A1 are involved in the aryl hydrocarbon receptor signaling pathway known to mediate dioxin toxicity. MYO1G, FRMD4A, ARL4C, OLFM1, and WWC3 were previously reported to be related to carcinogenesis. This is the first study examining genome-wide DNA methylation among people perinatally exposed to high concentrations of PCBs and PCDFs. We observed novel differential methylation of several genes, indicating that modifications of DNA methylation associated with perinatal PCB and PCDF exposure may persist in exposed offspring for more than 20 years. Furthermore, involvement of several carcinogesis-related genes suggested a potential in utero epigenetic mechanisms.