[The relationship between differentially expressed thyroid cancer genes and clinical characteristics in metastatic children and adolescents].

Objective: To investigate the relationship between genes and clinical characteristics in children and adolescents with metastatic differentiated thyroid cancer (caDTC). Methods: A cross sectional study. A total of 67 caDTC patients with lymph node metastasis or distant metastasis in Peking Union Medical College Hospital from December 2020 to December 2022 were included, according to the inclusion and exclusion criteria. Then the differences in clinicopathologic features and iodine intake were compared among different genomes, and the age subgroups divided by the age of 12 were further analyzed. Results: Among the 67 cases of caDTC, the diagnosed age [M(Q1, Q3)]was 13.2 (9.7, 16.9) years old, with 23 males and 44 females. There were 68.7% (46/67) of patients have distant metastasis (M1 stage). Pathogenic or potentially pathogenic gene variants were detected in 68.7% (46/67) of the patients, with RET or NTRK fusion (RET/NTRK) being the most common [43.3%(29/67)], BRAF V600E mutation followed [19.4%(13/67)].There was only 1 caDTC with NRAS Q61R mutation. The patients were divided into RET/NTRK fusion group (n=29), BRAF mutation group (n=12), other mutation group (n=4), and non-mutation group (n=21) (1 patient was not included in the gene mutation subgroup comparison due to the presence of NRAS Q61R mutation and BRAF V600E mutation). The comparison of gene feature groups showed that compared to the BRAF mutation group, caDTC with RET/NTRK fusion tended to have a lower age at diagnosis [12.6(9.3, 15.9) vs 17.2(15.5, 18.1) years old, P<0.001], the proportion of mutation load≥2 was higher (10.4% vs 8.3%, P=0.027), with statistically significant difference. Among 46 M1 stage patients, 71.7% (33/46) had initial iodine intake, and 30.4% (14/46) developed radioiodine-refractory (RAIR). In age group comparison, the<12 year old group had a higher proportion of male patients (51.9% vs 22.5%, P=0.013) and a lower incidence of BRAF V600E mutations (0 vs 32.5%, P<0.001) compared to the≥12 year old group, and the differences were statistically significant. Conclusions: The incidence of RET/NTRK fusion ranks first in metastatic caDTC, featured with younger age at diagnosis and higher rate of distant metastasis. Although most metastatic lesions initially consume iodine, they are prone to RAIR. Attention should be paid to the potential role of RET/NTRK fusion in the invasion and iodine resistance of young caDTC patients.

Isotopic Control of the Boron-Vacancy Spin Defect in Hexagonal Boron Nitride.

We report on electron spin resonance (ESR) spectroscopy of boron-vacancy (V_{B}^{-}) centers hosted in isotopically engineered hexagonal boron nitride (hBN) crystals. We first show that isotopic purification of hBN with ^{15}N yields a simplified and well-resolved hyperfine structure of V_{B}^{-} centers, while purification with ^{10}B leads to narrower ESR linewidths. These results establish isotopically purified h^{10}B^{15}N crystals as the optimal host material for future use of V_{B}^{-} spin defects in quantum technologies. Capitalizing on these findings, we then demonstrate optically induced polarization of ^{15}N nuclei in h^{10}B^{15}N, whose mechanism relies on electron-nuclear spin mixing in the V_{B}^{-} ground state. This work opens up new prospects for future developments of spin-based quantum sensors and simulators on a two-dimensional material platform.

[Analysis of mortality trend and characteristic of chronic obstructive pulmonary disease among residents in China from 2004 to 2020].

Objective: To analyze the mortality trend and characteristics of chronic obstructive pulmonary disease (COPD) among residents in China from 2004 to 2020. Methods: From the area, gender, region, and age dimensions, the Joinpoint regression model was used to analyze the trend of COPD mortality rate from 2004 to 2020, extracted from the China Death Surveillance Dataset. Results: From 2004 to 2020, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend (AAPC=-3.68%, P<0.001; AAPC=-7.27%, P<0.001), which were consistent with urban and rural subpopulations (mortality rate: AAPC=-3.62%, P=0.009, AAPC=-3.23%, P=0.014; age-adjusted mortality rate: AAPC=-7.26%, P<0.001, AAPC=-6.78%, P<0.001). The mortality rate of COPD in rural was higher than that of urban subpopulations (P<0.001). Also, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend in males and females (mortality rate: AAPC=-3.00%, P<0.001, AAPC=-4.37%, P<0.001; age-adjusted mortality rate: AAPC=-6.73%, P<0.001, AAPC=-8.11%, P<0.001), and the COPD mortality rate for male was generally higher than female (P<0.001). Meanwhile, the mortality rate of COPD in eastern, central and western regions also showed a downward trend (AAPC=-3.87%, P<0.001; AAPC=-3.12%, P<0.001; AAPC=-1.37%, P=0.001), and western regions were significantly higher than that in central (P<0.001) and eastern (P<0.001) regions. The mortality rate of COPD in the age group of Chinese people showed a downward trend in<45, 45-59, and≥60 years groups (AAPC=-9.48%, P<0.001; AAPC=-9.03%, P<0.001; AAPC=-5.91%, P<0.001). Among them,≥60 years groups was significantly higher than that in<45 (P<0.001) and 45-59 (P<0.001) years groups, and the decline rate was slowest. Conclusion: In China, the mortality rate of COPD decreases from 2004 to 2020, and more efforts are needed to reduce COPD mortality, especially in western regions, rural populations, males and the elderly.

Chinese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease have lower serum osteocalcin levels compared to individuals with type 2 diabetes mellitus and no liver disease: a single-center cross-sectional study.

PURPOSE: Osteocalcin may benefit nonalcoholic fatty liver disease (NAFLD). The present study aimed to explore the levels of serum osteocalcin in NAFLD in patients with type 2 diabetes mellitus (T2DM). METHODS: In total, 1026 inpatients diagnosed with T2DM were enrolled in the study. NAFLD was defined according to the working definition of the revised guidelines for the management of NAFLD published by the Chinese Liver Disease Association, and confirmed by abdominal ultrasonography. RESULTS: The current study found a NAFLD prevalence of 54% in the T2DM population. Subjects with NAFLD had lower concentrations of osteocalcin (8.28-13.99 ng/mL vs. 8.80-16.25 ng/mL, P = 0.001) but similar vitamin D, parathyroid hormone, beta-C-terminal telopeptide of type I collagen and procollagen type 1 N-peptide levels. Osteocalcin levels (OR: 0.956; 95% CI 0.926-0.987) were significantly associated with NAFLD. When all significant clinical indicators were analyzed together, increased BMI (OR: 1.120; 95% CI 1.065-1.178), fasting C-peptide (OR: 1.270; 95% CI 1.089-1.481) and triglycerides (OR: 1.661; 95% CI 1.284-2.148) were associated with a greater risk of NAFLD, while older age (OR: 0.967; 95% CI 0.948-0.986) and high osteocalcin levels (OR: 0.935; 95% CI 0.902-0.969) were related with a decreased risk of NAFLD. For every additional unit of osteocalcin, the patients received 7% deduced odds of NAFLD. CONCLUSION: Low osteocalcin levels were associated with an increased risk for NAFLD in patients with T2DM.

Effect of ambient air pollution exposure on renal dysfunction among hospitalized patients in Shanghai, China.

OBJECTIVES: We investigated whether long-term ambient air pollutants (AAP) exposure was associated with estimated glomerular filtration rate (eGFR) among hospitalized patients living in urban areas of Shanghai, China. STUDY DESIGN: This was a cross-sectional observational study. METHODS: A total of 3622 newly hospitalized inpatients were investigated from October 2014 to May 2015. The prior year's average exposure to particulate matter (PM) of each participant was estimated using the Kriging interpolation method of ArcGIS. The estimated eGFR was calculated according to the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Both generalized linear and logistic regression models were applied to assess the associations between AAP and renal function. RESULTS: One-year PM10 exposure was associated with lower eGFR; each standard deviation (SD) increase in PM10 was significantly associated with the increased prevalence of CKD [adjusted odds ratio (OR) 1.11; 95% confidence interval (CI): 1.02, 1.21], and lower eGFR by -0.40 (95%CI: -0.80, -0.01) ml/min/1.73 m2. Moreover, the effect of PM10 was significantly greater in people over 65 years old. CONCLUSION: Our results supported that exposure to ambient PM10 increased the risk of CKD and negatively affected renal function among Chinese adults.

[Safety and efficacy of regional transport combined with PCI model in patients with STEMI after thrombolysis in northwest China].

Objective: To investigate the safety and efficacy of regional transport to percutaneous coronary intervention(PCI) hospitals from non-PCI hospitals after thrombolysis in patients with acute ST-segment elevation myocardial infarction(STEMI) in northwest China. Methods: In this retrospective study, 1 062 STEMI patients who were transferred from non-PCI hospitals within 24 hours from symptom onset, during January 2015 and January 2019 in the First Hospital of Lanzhou University, were included. According to the treatment strategy, they were divided into two groups, namely intravenous thrombolysis combined with PCI group(n=240), and primary PCI group(n=822). Observation endpoint were in-hospital adverse cardiovascular and cerebrovascular events and bleeding events, Including all-cause death, ischemic stroke, malignant arrhythmia, intracranial hemorrhage and hemorrhage with hemoglobin decrease≥50 g/L. Results: A total of 1 062 STEMI patients were included(age was (61±12) years old), with 905 males (85.2%). The proportion of grade 0 TIMI blood flow in the primary PCI group before operation was significantly higher than that in the thrombolysis combined with PCI group(63.0%(518/822) vs. 36.3%(87/240)， P<0.001). Compared with primary PCI group, the time from symptom onset to first medical contact(2.11(1.00, 4.00)hours vs.3.00(1.13, 7.07)hours, P<0.001) and reperfusion in thrombolysis combined with PCI group(3.07(1.83, 4.87)hours vs. 6.92(4.07, 11.15) hours, P<0.001) were significantly shorter. The proportion of all-cause death was significantly higher in the primary PCI group than that in the thrombolysis combined with PCI group (1.8%(15/822) vs. 0, P=0.03). There was no significant difference in hemorrhage, ischemic stroke and malignant arrhythmia between the two groups(all P>0.05). Conclusions: For STEMI patients initially hospitalized in non-PCI hospitals, regional transport combined with PCI is feasible and effective. It does not significantly increase the risk of bleeding and cardiovascular and cerebrovascular events, with shorter time from symptom onset to myocardial reperfusion.

Phenotypic analysis of atopic dermatitis in children aged 1-12 months: elaboration of novel diagnostic criteria for infants in China and estimation of prevalence.

BACKGROUND: Atopic dermatitis (AD) is the most common skin disorder in infancy. However, the diagnosis and definite significance of infantile AD remains a debated issue. OBJECTIVE: To analyse the phenotypes of AD in infancy, to establish diagnostic criteria and to estimate the prevalence of this condition in China. METHODS: This is a multicentric study, in which 12 locations were chosen from different metropolitan areas of China. Following careful and complete history-taking and skin examination, the definite diagnosis of AD was made and the severity based on the SCORAD index was determined by local experienced dermatologists. Based on the detailed phenotyping, the major and representative clinical features of infantile AD were selected to establish the diagnostic criteria and evaluate their diagnostic efficacy. RESULTS: A total of 5967 infants were included in this study. The overall point prevalence of AD was 30.48%. The infantile AD developed as early as at the second month of life, and its incidence peaked in the third month of life at 40.81%. The proportion of mild, moderate and severe AD was 67.40%, 30.57% and 2.03%, respectively. The most commonly seen manifestations in the infantile AD were facial dermatitis (72.07%), xerosis (42.72%) and scalp dermatitis (27.93%). We established the novel diagnostic criteria of infants, which included: (i) onset after 2 weeks of birth; (ii) pruritus and/or irritability and sleeplessness comparable with lesions; and (iii) all two items above with one of the following items can reach a diagnosis of AD: (i) eczematous lesions distributed on cheeks and/or scalp and/or extensor limbs, and (ii) eczematous lesions on any other parts of body accompanied by xerosis. CONCLUSIONS: In China, the prevalence of AD in infancy is 30.48% according to clinical diagnosis of dermatologists. The novel Chinese diagnostic criteria for AD in infants show a higher sensitivity and comparable specificity.

Hypoxia-related gene expression in porcine skeletal muscle tissues at different altitude.

Hypoxia influences many physiological processes, such as respiration, cardiovascular, neurophysiology, and digestion. Skeletal muscle is an important motor organ, which relies on oxygen of oxidation; however, the study of hypoxia in skeletal muscle is lacking. In order to understand the effect of hypoxia on skeletal muscle, we determined the expression level of four hypoxia-related genes (ADAM17, ARG2, MMP, and HIF1A) in two distinct skeletal muscle tissues from Tibetan pigs that live at different altitudes (500 and 3650 m). Consistent with the well-characterized role of four hypoxia-related genes in the adaptation to high altitude, we found that, compared with the plain pigs, the plateau pigs had higher mRNA abundances of the four genes and lower myofiber ratio in skeletal muscle. The negative correlation between the myofiber ratio and mRNA abundance of the four hypoxia-related genes highlights their critical roles in skeletal muscle. These findings may be important for understanding skeletal muscle adaptation to high altitude and hypoxia-related muscle diseases in humans.

Association between a functional single nucleotide polymorphism in the brain-derived neurotrophic factor gene and risk of child asthma.

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. Allergic inflammation triggers neuronal dysfunction and structural changes in the airways. Genetic polymorphisms in functional regions of the BDNF gene have a plausible role in modulating the risk of child asthma (CA). This study examined the potential association between CA and three single nucleotide polymorphisms (SNPs) in BDNF (rs2030323, rs6265, and rs16917204 in the promoter, exon 4, and 3'-untranslated regions, respectively). The study was conducted in 350 children with asthma and 356 healthy controls. The genotype and allele frequencies and difference between groups were analyzed using HaploView 4.0 and SPSS 20.0 software platforms. The analysis revealed a strong association between the rs6265 genotype distribution and CA. The frequency of the G allele was significantly higher in CA patients than in healthy controls (P = 0.0007, odds ratio = 1.323, 95% confidence interval = 1.073-1.632). Strong linkage disequilibrium was observed between rs16917204 and rs6265. A significantly higher number of G-G haplotypes were observed in CA patients than in controls (P = 0.024 after Bonferroni correction), while the G-A haplotypes were more significant in controls (P = 0.013 after Bonferroni correction). This suggested that BDNF gene polymorphisms confer susceptibility to CA, and also support the notion that BDNF dysfunction is involved in the pathophysiological process of CA.

Involvement of ligninolytic enzymes in degradation of wheat straw by Trametes trogii.

AIMS: Wheat straw is generated in billions of tons around the world every year and has not been fully used. This study sought to evaluate the delignification capacity and enzyme production of Trametes trogii MT strain and to clarify the changes of structure and chemical composition of wheat straw during the decay process. METHODS AND RESULTS: The results obtained revealed that the T. trogii MT strain has the ability to degrade lignin, cellulose as well as hemicellulose of wheat straw simultaneously. The strain can produce high activities of laccase, manganese peroxidase, xylanase, carboxymethylcellulase and feruloyl esterase but no lignin peroxidases during the decay process of a 60-day incubation period on wheat straw. Scanning electron microscopy observation and infrared spectroscopy analysis showed the lignin and carbohydrate of wheat straw were degraded with no obvious different levels. The low molecular mass fractions collected from the culture of the MT strains grown in wheat straw powder liquid medium showed high Fe(3+) chelating, reducing capacity and hydroxyl radical and hydrogen peroxide generation. CONCLUSIONS: Trametes trogii MT has a complex mechanism to degrade lignocellulose, in addition to the extracellular enzymatic systems, and has great potential as an attractive micro-organism used for the biological degradation of waste straws. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed the dynamic changes of the ligninolytic enzymes of T. trogii MT during the degradation of wheat straw, and suggested that the decay patterns of wheat straw by T. trogii MT had some simultaneous type characteristics.

Effects of tetra-arsenic tetra-sulfide on BXSB lupus-prone mice: a pilot study.

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Arsenic trioxide (ATO) has been used in lupus-prone mice with a regulatory effect on immune abnormality. Tetra-arsenic tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects than ATO. In this study, a pilot study was performed to investigate the effects and the mechanism of As4S4 on the lupus-prone BXSB mice. Improvement of monocytosis (p<0.05) in spleen and decreased serum interleukin-6 (IL-6) (p=0.0277) were observed with As4S4 treatment. As4S4-treated mice exhibited amelioration of skin, liver and renal disease with mild side effects. Histological analysis revealed that As4S4 suppressed immune complex deposition, mesangial proliferation and inflammatory cell infiltration in kidney and liver. Our study support that As4S4 selectively suppresses cutaneous lupus and nephritis in BXSB mice and might be a potential treatment for SLE.

PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu.

The chromosomal translocation t(15;17)(q22;q12) is a consistent feature of acute promyelocytic leukemia (APL) that results in the disruption of genes for the zinc finger transcription factor PML and the retinoic acid receptor alpha (RAR alpha). We have previously shown that PML is a growth suppressor and is able to suppress transformation of NIH/3T3 by activated neu oncogene. In the study presented here, the full-length PML cDNA was transfected into B104-1-1 cells (NIH/3T3 cells transformed by the activated neu oncogene) by retrovirally mediated gene transfer. We found that expression of PML could reverse phenotypes of B104-1-1 including morphology, contact-limiting properties, and growth rate in both transient-expression and stable transfectants. We also demonstrated that PML is able to suppress clonogenicity of B104-1-1 in soft agar assay and tumorigenicity in nude mice. These results strongly support our previous finding that PML is a transformation or growth suppressor. Our results further demonstrate that expression of PML in B104-1-1 cells has little effect on cell cycle distribution. Western blot analysis demonstrated that suppression of neu expression in B104-1-1 by PML was insignificant in the transient transfection experiment but significant in the PML stable transfectants. This study suggests that PML may suppress neu expression and block signaling events associated with activated neu. This study supports our hypothesis that disruption of the normal function of PML, a growth or transformation suppressor, is a critical event in APL leukomogenesis.

Prevalence and types of androgenetic alopecia in Shanghai, China: a community-based study.

BACKGROUND: There are ethnic differences in the prevalence and types of androgenetic alopecia (AGA). Although there have been several reports on the prevalence and types of AGA in caucasian and Asian populations, there are very few data on a Chinese population that have been derived from a sufficient number of samples. OBJECTIVES: To estimate the prevalence and types of AGA in a Chinese population, and to compare the results with those in caucasians and Koreans reported previously in the literature. METHODS: A population-based cross-sectional study was carried out in 7056 subjects (3519 men and 3537 women) from May 2006 to December 2006 in a community of Shanghai. Questionnaires were completed during face-to-face interviews at the subjects' homes. The degree of AGA was classified according to the Norwood and Ludwig classifications. RESULTS: The prevalence of AGA in Chinese men was 19.9%, and the prevalence of female pattern AGA in men was 0.1%. The most common type in men was type III vertex (3.5%). The prevalence of AGA in women was 3.1%, while male pattern AGA was found in those aged over 50 years (0.4%), and the most common type was type I (Ludwig classification) (1.4%). A family history of AGA was present in 55.8% of men and 32.4% of women with AGA. CONCLUSIONS: The prevalence of AGA in Chinese men was lower than in caucasian men but was similar to that in Korean men; however, over the age of 60 years it was approaching that in caucasian men but was higher than that in Korean men. The most common type in Chinese men with AGA was type III vertex. Interestingly, the prevalence of AGA in Chinese women was lower than that in Korean women and caucasian women, and type I was the most common type (Ludwig classification).

PML, a growth suppressor disrupted in acute promyelocytic leukemia.

The nonrandom chromosomal translocation t(15;17)(q22;q21) in acute promyelocytic leukemia (APL) juxtaposes the genes for retinoic acid receptor alpha (RAR alpha) and the putative zinc finger transcription factor PML. The breakpoint site encodes fusion protein PML-RAR alpha, which is able to form a heterodimer with PML. It was hypothesized that PML-RAR alpha is a dominant negative inhibitor of PML. Inactivation of PML function in APL may play a critical role in APL pathogenesis. Our results demonstrated that PML, but not PML-RAR alpha, is a growth suppressor. This is supported by the following findings: (i) PML suppressed anchorage-independent growth of APL-derived NB4 cells on soft agar and tumorigenicity in nude mice, (ii) PML suppressed the oncogenic transformation of rat embryo fibroblasts by cooperative oncogenes, and (iii) PML suppressed transformation of NIH 3T3 cells by the activated neu oncogene. Cotransfection of PML with PML-RAR alpha resulted in a significant reduction in PML's transformation suppressor function in vivo, indicating that the fusion protein can be a dominant negative inhibitor of PML function in APL cells. This observation was further supported by the finding that cotransfection of PML and PML-RAR alpha resulted in altered normal cellular localization of PML. Our results also demonstrated that PML, but not PML-RAR alpha, is a promoter-specific transcription suppressor. Therefore, we hypothesized that disruption of the PML gene, a growth or transformation suppressor, by the t(15;17) translocation in APL is one of the critical events in leukemogenesis.

Bioinformatics Analysis on Molecular Mechanism of Green Tea Compound Epigallocatechin-3-Gallate Against Ovarian Cancer.

Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea, and it exerts multiple effects in humans through mechanisms that remain to be clarified. The present study used bioinformatics to identify possible mechanisms by which EGCG reduces the risk of ovarian cancer. Possible human protein targets of EGCG were identified in the PubChem database, possible human gene targets were identified in the National Center for Biotechnology Information database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis (IPA). The results suggest that signaling proteins affected by EGCG in ovarian cancer, which include JUN, FADD, NFKB1, Bcl-2, HIF1α, and MMP, are involved primarily in cell cycle, cellular assembly and organization, DNA replication, etc. These results identify several specific proteins and pathways that may be affected by EGCG in ovarian cancer, and they illustrate the power of integrative informatics and chemical fragment analysis for focusing mechanistic studies.

Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells.

Our previous studies demonstrated that the promyelocytic leukemia gene, PML, encodes a growth and transformation suppressor. Overexpression of PML inhibits cancer cell growth in vitro and in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-adenovirus, Ad-PML, in which the full-length PML cDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOI), respectively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3-4 postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOI of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were significantly inhibited. A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may be a potential candidate for human prostate cancer therapy.

[The study of atmospheric particulate matters and IFN-γDNA methylation in CD4⁺ T cells from patients with AR children].

Objective:To investigate the possible effects of meteorological and environmental factors on AR of children and IFN-γgene specific DNA methylation levels in CD4⁺ T cells of patients with AR. Method:Undergoing follow-up on 35 pediatric AR patients (6-12 years). Data on daily sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter of diameter smaller than 10 micrometer (PM-10) and particulate matter of diameter smaller than 2.5 micrometer (PM2.5), the average of ozone (O3) per 8 hours was available as average values derived from the data of 6 state controlled monitoring stations distributed across Pudong district, Shanghai. We quantified IFN-γ (interferon-γ) gene specific DNA methylation levels in CD4⁺ T cells from 35 patients with AR and 30 healthy controls. mRNA levels of IFN-γ gene were measured by real-time reverse transcriptase-PCR. Methods of personal exposure assessment of PM2.5 and PM10 were measured. Result:Compared with control, IFN-γ promoter region was hypermethylated in AR CD4⁺ T cells (P<0.05). Of all observed CpG sites in IFN-γ promoter region, there were significant differences in CpG⁻²99, CpG⁺¹¹9, CpG⁺¹68 (P=0.004, P=0.029, P=0.035). IFN-γ mRNA expression was significantly increase in CD4⁺ T cells (P<0.05). The level of IFN-γ mRNA expression was negatively correlated to mean level of methylation in IFN-γ promoter region. After adjusting, level of long exposure PM2.5 was positively correlated with level of methylation in IFN-γ promoter region. Conclusion:Level of methylation in IFN-γ promoter region may be affected by long exposure PM2.5.

Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis.

Our previous studies demonstrated that the promyelocytic leukemia gene, PML which involved in the 15;17 translocation in acute promyelocytic leukemia (APL) is a growth and transformation suppressor. In this study, recombinant PML adenovirus, Ad-PML was constructed and used to infect human breast cancer cells in vitro and in vivo, the anti-oncogenic function of PML and its mechanism of growth suppressing effect in breast cancer cells were examined. We showed that Ad-PML effectively infected the MCF-7 and SK-BR-3 cells. A high level of PML protein was expressed within 24 h post-infection and a detectable level remained at day 16. Ad-PML significantly suppressed the growth rate, clonogenicity, and tumorigenicity of breast cancer cells. Intratumoral injections of MCF-7-induced tumors by high titer Ad-PML suppressed tumor growth in nude mice by about 80%. The injection sites expressed high level of PML and associated with a massive apoptotic cell death. To elucidate the molecular mechanism of PML's growth suppressing function, we examined the effect of Ad-PML on cell cycle distribution in MCF-7 and SK-BR-3 cells. We found that Ad-PML infection caused a cell cycle arrest at the G1 phase. We further showed that G1 arrest of MCF-7 cells is associated with a significant decrease in cyclin D1 and CDK2. An increased expression of p53, p21 and cyclin E was found. The Rb protein became predominantly hypophosphorylated 48 h post-infection. These findings indicate that PML exerts its growth suppressing effects by modulating several key G1 regulatory proteins. Our study provides important insight into the mechanism of tumor suppressing function of PML and suggests a potential application of Ad-PML in human cancer gene therapy.