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Background Although programmed cell death‐ligand 1 (PD‐L1) plays a well‐known function in immune checkpoint response by interacting with programmed cell death‐1 (PD‐1), the cell‐intrinsic role of PD‐L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD‐L1 in the progression and metastasis of ovarian cancer. Methods Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD‐L1‐knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD‐L1 in ovarian cancer. Results Our results showed that PD‐L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD‐L1 was identified to directly interact with vascular endothelial growth factor receptor‐2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD‐L1 was found to be regulated by the oncogenic transcription factor c‐JUN at the transcriptional level, which enhanced the expression of PD‐L1 in ovarian cancer. Furthermore, we demonstrated that PD‐L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti‐angiogenesis and the inhibition of cell migration and invasion. Conclusion Our results demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, suggesting that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients., This manuscript demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, and suggested that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

Objective To investigate the urodynamic study (UDS) result in pediatric patients with spastic cerebral palsy (CP). Material and methods Medical records of CP with pre-operative UDS results underwent selective dorsal rhizotomy (SDR) from Jan. 2020 to May. 2021 were retrospectively reviewed. Results Fifty-seven cases with spastic CP were included in the study. Among these cases, 46 were ambulatory and 11 were non-ambulatory. Average gross motor function measure - 66 (GMFM - 66) score was 62.16 ± 11.39. Reduced bladder capacity was seen in 49.12% of these cases and cases with lower GMFM - 66 score had a higher incidence rate of having low bladder capacity (p < 0.01). Detrusor overactivity (DO) was shown in 33.33% of patients. Cases with younger age had higher prevalence of DO (p < 0.05). Meanwhile, more non-ambulant patients had DO (p < 0.05). Increased post-voiding residual (PVR) was seen in 21.05% of cases. Those with higher average threshold in sphincter-associated input spinal nerve roots (rootlets) had higher rate of having abnormal PVR (p < 0.05). Conclusion Abnormal UDS results were prevalent in pediatric spastic CP. Motor function, age and threshold of their sphincter-associated spinal nerve rootlets were related to the abnormal UDS results.

Background: Due to its high ability of metastasis, ovarian cancer remains the most lethal gynecological malignancy, yet its underlying mechanism remains unconfirmed. Objectives: The main purpose is to probe into the role and regulation mechanism of octamer-binding transcription factor 4 (OCT4) in angiogenesis and metastasis in ovarian cancer.Methods: Immunohistochemistry (IHC) and immunofluorescence in epithelial ovarian cancer specimens and benign ovarian tumor samples were performed, followed by RNA-sequencing and examination of angiogenesis, cell migration and invasion in OCT4 knockdown cell lines and the controls. Co-Immunoprecipitation (Co-IP), mass spectrometry, immunoblotting, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses were conducted along with models of zebrafishes and nude mice of transplanted tumors to gain insights into the specific functions and mechanisms of action of OCT4 in ovarian cancer.Results: Firstly, we discovered that OCT4 expression was enhanced in ovarian cancer tissues significantly, especially in the metastatic lesions, indicating that OCT4 might be a key for the metastasis of ovarian cancer. Furtherly, we observed and verified that OCT4 promoted cell migration and invasion, and induced angiogenesis in vitro and in vivo. Mechanistically, OCT4 modulated the transcription of leucine‑rich PPR motif‑containing protein (LRPPRC)，and furtherly interacted with vascular endothelial growth factor receptor 2 (VEGFR2)/LRPPRC complex and ultimately triggered the downstream FAK/AKT signaling pathway . Conclusions: Together, through models of ovarian cancer cells, zebrafishes and tumor-transplanted mice, this study highlighted the importance of OCT4/LRPPRC/VEGFR2 signaling axis in metastasis of ovarian cancer and angiogenesis. Thus, our finding supplied a potential novel molecular-targeted approach for the treatment of ovarian cancer.

This abstract was not presented at the conference. Citation Format: Zhao Y, Sun H, Jin W. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-08-08.

The relations of polycyclic aromatic hydrocarbons (PAHs) exposure with platelet indices remain unclear. Based on the baseline data from the Wuhan-Zhuhai Cohort Study, we used generalized linear model, multivariate logistic regression analysis and restricted cubic splines (RCS) to assess linear and nonlinear relationship of PAHs exposure with platelet indices. The results showed that among Wuhan individuals, there were the non-linear relations between total hydroxynaphthalene (ΣOHNa) and mean platelet volume (MPV) or ratio of mean platelet volume to platelet count (MPVP), total hydrophenanthrene (ΣOHPh) and MPV or platelet distribution width (PDW), the sum concentration of urinary monohydroxylated metabolites of PAHs (ΣOH-PAHs) and ratio of platelet count to lymphocyte count (PLR) or MPVP, 1-hydropyrene (1-OHP) and PLR or PDW. But among Zhuhai individuals, neither linear nor non-linear relations were found between each of OH-PAHs or ΣOH-PAHs and platelet indices. The findings indicate that serum MPV and MPVP may be independent biomarkers of effects of exposing to environmental PAHs on human bodies.

Background So far, the prevalence of human T-lymphotropic virus (HTLV) type 1 and 2 in some highly populated countries such as China is still unknown. In this study, a multi-center nationwide serological survey was designed and performed, to reveal the seroprevalence of HTLV infection among Chinese blood donors. Results Among 8,411,469 blood donors from 155 blood establishments, 435 were finally confirmed as HTLV carriers. The prevalence of HTLV infection in China varied in different provinces: Fujian had the highest prevalence of 36.240/100,000 (95% CI 31.990–41.050) and eleven provinces did not find HTLV-seropositive donors in the three years. no HTLV-2 infection was found. The overall prevalence of HTLV-1 in China decreased from 2016 to 2018. Female was identified as an independent risk factor of HTLV infection in China. Besides, seroconversion was observed in two of seven seroindeterminate donors 85 and 250 days after their last donation, respectively. Conclusions The seroprevalence of HTLV infection in most areas of China among blood donors is quite low, but it varies significantly in different geographic areas. Screening anti-HTLV-1/2 antibody and follow-up of serointederminate donors are essential to ensure blood safety especially in areas where we have found HTLV infected donors.

Hepatitis B virus (HBV) infection is a major threat to global public health, which can result in many acute and chronic liver diseases. HBV, a member of the family Hepadnaviridae, is a small enveloped DNA virus containing a circular genome of 3.2 kb. Located upstream of the S-open-reading frame of the HBV genome is the pre-S region, which is vital to the viral life cycle. The pre-S region has high variability and many mutations in the pre-S region are associated with several liver diseases, such as fulminant hepatitis (FH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). In addition, the pre-S region has been applied in the development of several pre-S-based materials and systems to prevent or treat HBV infection. In conclusion, the pre-S region plays an essential role in the occurrence, diagnosis, and treatment of HBV-related liver diseases, which may provide a novel perspective for the study of HBV infection and relevant diseases.

Serological tests have been widely used for detecting human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibodies in the endemic areas, but their performance in low-risk populations is rarely reported. The aim of this study was to evaluate the performance of four HTLV-1/2 screening assays and to discuss a strategy for diagnosis of HTLV-1/2 infection in a non-endemic area. At the present study, 1546 specimens repeatedly reactive (RR) by one screening ELISA were collected from blood centers/banks from January 2016 to April 2019. Avioq-ELISA, Murex-ELISA, Roche-ECLIA and Fujirebio-CLIA were independently performed on each plasma sample and compared to WB and LIA confirmatory tests. Positive or indeterminate specimens with blood available were quantified by qPCR. The results showed that 48 samples were finally confirmed as HTLV-1 positive, 13 were HTLV positive, 151 were indeterminate, and 387 were negative. All the WB-positive samples were also LIA-positive. Roche-ECLIA showed the highest sensitivity that was able to detect 91.8% positives and combined with the Murex-ELISA would significantly increase the positive detection rate (98.4%). In addition, LIA yield more indeterminate and HTLV-untyped results than WB (152 vs. 27), but was able to resolve infection status of some individuals with an indeterminate WB. Besides, 3 WB indeterminate and 1 LIA-untyped samples were confirmed as HTLV-1 positive by qPCR. Based on these findings, we put forward a proper test strategy for HTLV-1/2 diagnosis in low-prevalence areas. If possible, the Roche-ECLIA with the highest sensitivity is suggested as a second screening assay in primary labs. If not, all RR specimens are recommended to be firstly retested by Roche-ECLIA and Murex-ELISA in the reference lab. Secondly, samples reactive to any one of the two tests were quantified by qPCR, and then the NAT-negatives were furtherly submitted to LIA for confirmation. Thereby, the cost can be reduced and the diagnostic accuracy would be improved.

Although COVID-19 pediatric patients just account for 1% of the overall cases, they are nonnegligible invisible infection sources. We quantitatively analyzed the clinical and epidemiological features of 82 confirmed cases aged 0-16 admitted to Wuhan Children’s Hospital, which are expected to shed some lights onto the pediatric diagnosis and therapy.

Background Ovarian cancer remains the most lethal gynecologic malignancy. In this study, we aimed to identify the specific risk factors affecting overall survival (OS) and develop a nomogram for prognostic prediction of ovarian cancer patients based on data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods Information from the SEER database on ovarian cancer between 2004 and 2016 was screened and retrieved. Cases were randomly divided into the training cohort hand the validation cohort at a 7:3 ratio. The prognostic effects of individual variables on survival were evaluated via Kaplan-Meier method and Cox proportional hazards regression model using data from the training cohort. A nomogram was formulated to predict the 3- and 5-year OS rates of patients with ovarian cancer, and then validated both in the training cohort and the validation cohort. Results A total of 28,375 patients were selected from 75,921 samples (19,862 in training cohort and 8,513 in validation cohort). Cox regression analysis identified race, age laterality, histology, stage, grade, surgery, chemotherapy, radiotherapy, and marital status as independent risk factors for ovarian cancer prognosis. A nomogram was developed based on the results of multivariate analysis and validated using an internal bootstrap resampling approach, which demonstrated a sufficient level of discrimination according to the C-index (0.752, 95% CI: 0.746–0.758 in the training cohort, 0.755, 95% CI: 0.746–0.764). Conclusions We developed a nomogram valuable for accurate prediction of 3- and 5-year OS rates of ovarian cancer patients based on individual characteristics.

Exposure to Polycyclic aromatic hydrocarbons (PAHs) has been associated with inflammatory responses. Fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) are both important inflammatory mediators especially in airways. However, few studies have investigated associations of PAH exposures with FeNO or eCO. Therefore, we aimed to quantify the associations of urinary PAH metabolites with FeNO and eCO levels, and investigate their potential effect modifiers by linear mixed models among 4133 participants from the Wuhan-Zhuhai cohort in China. We further performed stratified analyses to estimate effect modification. We found significant associations of increased urinary PAH metabolites with elevated eCO and FeNO. Among all participants, each 1% increase of 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 3-hydroxyphenanthrene, and total PAH metabolites was significantly associated with a 12.6% (95% confidence interval: 9.3%, 15.9%), 9.7% (6.5%, 12.9%), 7.5% (4.1%, 10.9%), 3.2% (0.2%, 6.2%), 2.7% (0.1%, 5.3%), and 6.5% (2.7%, 10.4%) increased eCO level, respectively; while each 1% increase of urinary 1-hydroxynaphthalene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 2-hydroxyphenanthrene was associated with a -3.0% (-5.8%, -0.2%), 2.9% (0.3%, 5.6%), 3.2% (1.0%, 5.4%), and 4.5% (2.2%, 6.9%) change of FeNO level, respectively. Positive associations between certain urinary PAH metabolites and eCO were observed among both ever-smokers and non-smokers, and the associations were stronger among ever-smokers than that among non-smokers. Increased urinary PAH metabolites were associated with decreased FeNO among ever-smokers and elevated FeNO levels among non-smokers. Our findings suggest that PAH exposures may impair airway through inducing inflammatory response, especially among ever-smokers.

Background Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. Case presentation Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. Conclusion Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse effects on the respiratory system. However, the association between internal levels of PAH metabolites and lung function levels remains unclear.We investigated the relationships between urinary PAH metabolite concentrations and lung function levels in a general Chinese population.Lung function and 12 urinary PAH metabolites were measured in 2,747 participants from the Wuhan-Zhuhai cohort in China. Associations between urinary PAH metabolites and lung function were analyzed by linear mixed models. We also investigated associations among urinary PAH metabolite concentrations, traffic exposure time, and dietary PAH exposure.We found significant associations between increased levels of urinary PAH metabolites and reduced lung function. Each 1-U increase in log-transformed levels of 2-hydroxynaphthalene, 9-hydroxyfluorene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 1-hydroxypyrene, or total urinary PAH metabolites was associated with a 23.79-, 19.36-, 41.76-, 36.87-, 33.47-, 27.37-, 39.53-, 34.35-, 25.03-, or 37.13-ml reduction in FEV1, respectively (all P 0.05). Each 1-U increase in 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, or total urinary PAH metabolites was associated with a 24.39-, 33.90-, 27.15-, 28.56-, 27.46-, or 27.99-ml reduction in FVC, respectively (all P 0.05). The total urinary PAH metabolites concentration was positively associated with both traffic exposure time and dietary PAH exposure among nonsmokers.Total and specific urinary PAH metabolites were associated with lung function reduction in a general Chinese population. Further studies are needed to investigate the potential mechanism by which PAHs induces lung function reduction.

Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with increased risk of diabetes, whereas socioeconomic status (SES) may contribute to the development of diabetes. However, the mechanisms underlying the relationships between them are unclear. We used structural equation modeling (SEM) to identify mediating factors in the associations of PAHs exposure, low SES with diabetes risk. Data were collected from 2751 Wuhan participants at baseline from the Wuhan-Zhuhai Cohort Study (n = 3053). They answered the questionnaires regarding socio-demographic, participated physical examinations and provided urine samples for measurements of urinary monohydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) levels. SEM was used to identify the mediating factors (such as hypertension, body mass index (BMI), triglycerides (TG) and total cholesterol (TCHO)) in the associations of low SES or PAHs exposure with diabetes risk. We observed that partial effect of PAHs exposure (β = 0.281, p = 0.034), BMI (β = 0.182, p = 0.000), TG (β = 0.358, p = 0.000), TCHO (β = 0.203, p = 0.009) or hypertension (β = 0.385, p = 0.000) on diabetes was directive. Moreover, low SES also exhibited a directive effect on PAHs exposure (β = −0.084, p = 0.000), BMI (β = 0.301, p = 0.000), hypertension (β = 0.134, p = 0.003) and TG (β = 0.087, p = 0.001). PAHs exposure directly affected TCHO levels (β = 0.080, p = 0.002) and TG (β = 0.076, p = 0.017). The proportion of the effect of PAHs exposure on diabetes mediated by TG and TCHO was 15.6%. The proportion of the effect of low SES on diabetes mediated by BMI, hypertension and TG was 89.1%. The results suggested that low SES increased diabetes risk, which may be partially explained by BMI, hypertension and triglycerides, and exposure to high levels of PAHs may have indirect contribution to increased risk for diabetes with dyslipidemia.

Background This study aimed to investigate and analyze the status of internal quality control (IQC) for BNP and NT-proBNP from 2014 to 2017, so as to have an integral understanding of quality performance of measurement in clinical laboratories in China. Methods The 4-year IQC information for BNP and NT-proBNP of participant laboratories were collected through EQA reporting system. Percentages of laboratories meeting different quality requirements (pass rates) for current coefficient of variations (CVs) were calculated afterwards. Further analysis for current CVs and pass rates among different years and measurement systems were conducted. Finally, we analyzed and summarized IQC practice and its changes in 4 years. Results The current CVs for BNP and NT-proBNP have decreased significantly from 2014 to 2017, and pass rates both presented significant increasing trends. NT-proBNP had higher pass rates than BNP regardless of 1/3TEa or 1/4TEa specification was used. The main measurement systems for two analytes were different. For NT-proBNP, current CVs of Roche has decreased significantly among 4 years and were significantly lower than Radiometer and BioMerieux in 2015. Current CVs of Abbott also had decreasing tendency for BNP. Analysis of IQC practice indicated that control rules and IQC frequency had made great progress in 4 years. Conclusion The imprecision performance of measurement of BNP and NT-proBNP has improved with decreasing of current CVs and increasing of pass rates in 4 years. However, it still needs continual improvement. Clinical laboratories in China should take active actions to promote performance of BNP and NT-proBNP measurement.

To investigate the effects of the urinary metabolite profiles of background exposure to the atmospheric pollutants polycyclic aromatic hydrocarbon (PAH) and Framingham risk score (FRS), which assesses an individual's cardiovascular disease risk, on heart rate variability (HRV).The study conducted from April to May 2011 in Wuhan, China, included 1978 adult residents with completed questionnaires, physical examinations, blood and urine samples, and 5-min HRV indices (including SD of all normal to normal intervals (SDNN), root mean square successive difference (rMSSD), low frequency (LF), high frequency (HF) and their ratio (LF/HF), and total power) obtained from 3-channel Holter monitor. 12 urinary PAH metabolites were measured by gas chromatography-mass spectrometry. FRS was calculated by age, sex, lipid profiles, blood pressure, diabetes and smoking status. Linear regression models were constructed after adjusting for potential confounders.Elevated total concentration of hydroxynaphthalene (ΣOHNa) was significantly associated, in a dose-responsive manner, with decreased SDNN and LF/HF (ptrend=0.014 and 0.007, respectively); elevated total concentration of hydroxyfluorene (ΣOHFlu) was significantly associated with reduced SDNN, LF and LF/HF (ptrend=0.027, 0.003, and0.0001, respectively); and elevated total concentration of all PAH metabolites (ΣOH-PAHs) was associated with decreased LF and LF/HF (ptrend=0.005 and0.0001, respectively). Moreover, increasing quartiles of FRS were significantly associated with decreased HRV indices, except LF/HF (all ptrend0.0001). Interestingly, individuals in low-risk subgroups had greater decreases in SDNN, LF and LF/HF in relation to ΣOH-PAHs, ΣOHNa and ΣOHFlu than those in high-risk subgroups (all p0.05).Environmental PAH exposure may differentially affect HRV based on individual coronary risk profiles.

To establish a simple and rapid method to remove serosa and mucosa from detrusor for the culture of bladder smooth muscle cells (SMCs).Fourteen New Zealand rabbits were randomly allocated to two groups. In the first group, pure bladder detrusor was directly obtained from bladder wall using novel method characterized by subserous injection of normal saline. In the second group, full thickness bladder wall sample was cut down, and then, mucosa and serosa were trimmed off detrusor ex vivo. Twelve detrusor samples from two groups were manually minced and enzymatically digested, respectively, to form dissociated cells whose livability was detected by trypan blue exclusion. Proliferative ability of primary culture cells was detected by CCK-8 kit, and purity of second-passage SMCs was detected by flow cytometric analyses. Another two detrusor samples from two groups were used for histological examination.Subserous injection of normal saline combined with blunt dissection can remove mucosa and serosa from detrusor layer easily and quickly. Statistical analysis revealed the first group possessed higher cell livability, shorter primary culture cell doubling time, and higher purity of SMCs than the second group (P0.05). Histological examination confirmed no serosa and mucosa existed on the surface of detrusor obtained by novel method, while serosa or mucosa residual can be found on the surface of detrusor obtained by traditional method.Pure detrusor can be acquired from bladder wall conveniently using novel method. This novel method brought about significantly higher purity and cell livability as compared to traditional method.

Health conditions may greatly modify the association between particulate matter (PM) and heart rate variability (HRV), but whether the modification of PM effect by coronary artery disease (CAD) risk status depends on the PM levels remains unknown. We investigated the associations between personal exposures to PM with aerodynamic diameter of ≤10μm (PM10) and ≤2.5μm (PM2.5) and concurrent HRV, and whether the effect of PM on HRV was modified by Framingham risk score (FRS) in healthy subjects with different PM exposure levels. Personal exposures to PM10 and PM2.5 were measured for 24h in 152 volunteers of community residents who were free of cardiovascular disease in two cities (Zhuhai and Wuhan) that differ in air quality. Simultaneously, 24h HRV indices were obtained from 3-channel Holter monitor. FRS was calculated based on age, sex, lipid profiles, blood pressure, diabetes, and smoking status. Linear regression models were constructed after adjusting for potential confounders. We found significant decrease in total power (TP) and low power (LF) with increased PM10 concentrations (P for trend

OBJECTIVE To investigate indoor factors affecting fractional exhaled nitric oxide (FeNO) in community residents. METHODS A total of 2404 adults (865 men, 1539 women, mean age 51.7 ± 13.3 years) were recruited to the study. Factors affecting FeNO were analyzed by multiple linear regression analysis. RESULTS Participants without a kitchen exhaust fan/hood had higher FeNO (GM: 10.21%, 95% CI: 4.18%-16.59%). Participants engaged in home cooking who used only liquefied petroleum gas had higher FeNO (GM: 5.75%, 95% CI: 0.10%-11.73%) compared to those using natural gas for residential (home) cooking. CONCLUSION Nonuse of a kitchen exhaust fan/hood and use of liquefied petroleum gas among persons engaged in home cooking were associated with higher FeNO levels.

Background Particulate air pollution has been recognized to be associated with a wide range of adverse health effects, including increased mortality, morbidity, exacerbation of respiratory conditions. However, earlier physiological or pathological changes or long-term bodies’ reaction to air pollutants have not been studied in depth in China. The Wuhan-Zhuhai (WHZH) cohort study is designed to investigate the association between air pollutants exposure and physiological or pathological reactions on respiratory and cardiovascular system. Methods/Design The cohort is a community-based prospective study that includes 4812 individuals aged 18–80 years. The collections of data were conducted from April to May 2011 in Wuhan city and in May 2012 in Zhuhai city. At baseline, data on demographic and socioeconomic information, occupational history, family disease history, lifestyle, cooking mode, daily travel mode, physical activity and living condition have been collected by questionnaires. Participants underwent an extensive physical examination, including anthropometry, spirometry, electrocardiography, and measurements of blood pressure, heart rate, exhaled nitric oxide and carbon monoxide. Potential conditions in the lung, heart, liver, spleen, and skin were synchronously performed. In addition, samples of morning urine, fasting blood serum and plasma were collected during physical health examination. DNA were extracted and were stored at -80°C. Environment concentrations of particulate matter and chemicals were determined for 15 days in each of four seasons. Participants are followed for physiological or pathological changes or incidence of cardiopulmonary diseases every 3 years. Discussion The results obtained in WHZH cohort study may increase a better understanding of the relationship between particulate air pollution and its components and possible health damages. And the potential mechanisms underlying the development of cardiopulmonary diseases has implications for the development of prevention and treatment strategies.

Background Ageing is related to the risk of many diseases and is affected by genetic, epigenetic, and environmental factors. Exposure to the ubiquitous pollutant polycyclic aromatic hydrocarbons (PAHs) is known to cause health damage, but the relation between such exposure with methylation ageing has not been studied. We undertook an association analysis of exposure to PAHs and DNA methylation ageing, a novel and promising ageing marker. Methods We built a model of methylation age and defined two ageing indicators (ageing rate, calculated as ratio of methylation to chronological age; and Δage, calculated as methylation minus chronological age) on the basis of genome-wide methylation data of blood in five panels of Chinese individuals (N=596). Participants included 137 coke oven workers (aged 26–60 years) who were chronically and occupationally exposed to high levels of PAHs; 101 patients with acute coronary syndrome (aged 40–86 years) from Wuhan, China; 97 patients with this syndrome (aged 38–83 years) from Guangdong, China; 162 healthy individuals (aged 26–79 years) from Wuhan; and 99 healthy individuals (aged 37–80 years) from Zhuhai, China. Exposure to individual PAHs was assessed by ten urinary PAH metabolites. We examined the relations between PAH exposure and the two ageing indicators, and investigated the potential CpGs mediating the association. Written informed consent was obtained from all participants. Our study was approved by the ethics committee of Tongji Medical College, Wuhan, China. No study subjects were from clinical trials. Findings Coke oven workers, who were exposed to high levels of PAHs at work (mean nature-log-transformed total urinary PAHs −1·909 [SD 0·461]), had significant age acceleration (2·7% increase in ageing rate [p=0·002] and 1·218-year increase in Δage [p=0·01] compared with all other panels). Urinary 3-OH-phenanthrene and 9-OH-phenanthrene were independently and significantly associated with the two ageing indicators in our non-disease panels. One unit increase of nature-log-transformed 9-OH-phenanthrene was associated with a 1·8% increase (p=0·0029) in ageing rate and a 1·1-year increase (p=0·0002) in Δage, whereas for 3-OH-phenanthrene the increase was 1·3% (p=0·0050) for ageing rate and 0·57 year (p=0·0109) for Δage. Methylation at several ageing-related and PAH-related CpGs (annotated on ELOVL2 , KLHL35 , FHL2 , BOK , PDP1 , and OTUD7A ) was reported to mediate the effect of PAH exposure on methylation ageing. Interpretation Our study revealed a significant association between PAH exposure and accelerated methylation ageing. The importance of exposure-related ageing needs to be further investigated. Funding National Key Basic Research and Development Program, Natural National Scientific Foundation, the 111 Project, the Program for Changjiang Scholars, and Innovative Research Team Scholars.

Background: Breast cancer is the chief culprit leading to woman's death. The major cause is the chemoresistance and distant metastasis before or after surgery and standard treatment. Recent studies suggest that chemokines and their receptors may play important roles in breast cancer metastasis and chemoresistance. Purpose: The chemokine receptor CXCR2 is associated with tumor development in many cancers. Although IL-8 and Gro-alpha as the major ligands contribute to breast cancer progression, the function of their receptor CXCR2 in breast cancer is elusive. In this study, we investigated the role of CXCR2 in breast cancer metastasis and chemoresistance. Experimental design:Human breast cancer cell lines including MCF-7 and SKBR-3 (low metastasis), MDA-MB-231 (medium metastasis), MDA-MB-231HM (high lung metastasis), MDA-MB-231BO (high bone metastasis), and MDA-MB-231/Gem (Gemcitabine-resistant) were used to investigate cell proliferation, migration, invasion, colony formation, apoptosis, and tumorigenesis by MTT, scratch-wound, transwell, soft agar, flow cytometery, and animal assays after CXCR2 or its associated proteins were over expressed or silenced/inhibited. Protein expression in cell lines and tissues was examined by either Western blot, ELISA, immunofluorescence, or immunohistochemical staining. Results: CXCR2 expression was higher in chemoresistant breast cancer cell lines, high-metastatic cell lines and breast cancer tissues than in chemosensitive cell lines, low-metastatic cell lines, and breast cancer tissues. Overexpression of CXCR2 promoted cell proliferation, migration, invasion, cell anti-apoptosis, tumor formation, metastasis, and chemoresistance, but silencing of CXCR2 inhibited those activities both in vitro and in vivo. Mechanism studies revealed that CXCR2 suppresses AKT1 to promote breast cancer metastasis and chemoresistance through cyclooxygenase-2 (COX-2; PTGS2) to regulate caveolin-1, MMP2, MMP9, E-cardherin, and beta-catenin, which can be inversed by knock down of CXCR2 or COX-2, and over expression of AKT1 and P85alpha. Additionally, over expression of CXCR2 and COX-2, or silencing of PI3K/AKT1 inhibits p53 phosphorylation (Serine 15) and E2F1 expression, but activates MDM2, Bcl-xL and Bcl-2, leading to increased anti-apoptosis. Tissue microarray analysis from 300 breast cancer patients also indicated that over expression of CXCR2 is associated with enhanced COX2 expression and reduced AKT1 expression in metastatic and chemoresistant breast carcinomas (P < 0.001), which may be used to predict breast cancer development. Conclusions: Our results suggest that CXCR2 controls breast cancer metastasis and chemoresistance through regulating COX-2 and AKT1. Thus, antagonists of CXCR2 and COX-2 may be used synergistically to treat breast cancer patients particularly with high metastasis and chemoresistance. Citation Format: Han Xu, Fengjuan Lin, Ziliang Wang, Jiao Meng, Huizhen Sun, Zihao Qi, Yan Wang, Zhouluo Ou, Zhimin Shao, Genhong Di, Gong Yang. CXCR2 controls breast cancer metastasis and chemoresistance through PI3K/AKT and COX-2 signalings. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 548. doi:10.1158/1538-7445.AM2013-548 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.