[Analysis of the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019].

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.

Long non-coding RNA PVT1 facilitates cell migration and invasion by regulating miR-148a-3p and ROCK1 in breast cancer

PurposeBreast cancer (BC) is one of the most common malignant tumors for women. The role and potential mechanisms of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) were explored in BC cell migration and invasion.MethodsPVT1, miR-148a-3p and Rho‑associated, coiled‑coil containing protein kinase 1 (ROCK1) mRNA expressions were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROCK1 protein expression was detected by Western blotting. The relationship of PVT1, miR-148a-3p and ROCK1 was analyzed by Dual Luciferase activity, RNA immunoprecipitation (RIP) and Spearman correlation analysis. Cell invasion and migration were detected by Transwell assay.ResultsUpregulation of PVT1 and ROCK1, and downregulation of miR-148a-3p were observed in BC tissues and cell lines. According to the analysis of Dual Luciferase activity, RIP and Spearman correlation analysis, miR-148a-3p directly binds to PVT1, and ROCK1 is a target of miR-148a-3p. In addition, PVT1 regulated the cells migration and invasion by regulating miR-148a-3p and ROCK1 expression.ConclusionThese data demonstrated that PVT1 was upregulated and facilitated to the cell migration and invasion of BC by the regulation of miR-148a-3p and ROCK1, indicating that PVT1 may be a potential biomarker of BC diagnosis and treatment.

Long non-coding RNA PVT1 facilitates cell migration and invasion by regulating miR-148a-3p and ROCK1 in breast cancer.

PURPOSE: Breast cancer (BC) is one of the most common malignant tumors for women. The role and potential mechanisms of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) were explored in BC cell migration and invasion. METHODS: PVT1, miR-148a-3p and Rho­associated, coiled­coil containing protein kinase 1 (ROCK1) mRNA expressions were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROCK1 protein expression was detected by Western blotting. The relationship of PVT1, miR-148a-3p and ROCK1 was analyzed by Dual Luciferase activity, RNA immunoprecipitation (RIP) and Spearman correlation analysis. Cell invasion and migration were detected by Transwell assay. RESULTS: Upregulation of PVT1 and ROCK1, and downregulation of miR-148a-3p were observed in BC tissues and cell lines. According to the analysis of Dual Luciferase activity, RIP and Spearman correlation analysis, miR-148a-3p directly binds to PVT1, and ROCK1 is a target of miR-148a-3p. In addition, PVT1 regulated the cells migration and invasion by regulating miR-148a-3p and ROCK1 expression. CONCLUSION: These data demonstrated that PVT1 was upregulated and facilitated to the cell migration and invasion of BC by the regulation of miR-148a-3p and ROCK1, indicating that PVT1 may be a potential biomarker of BC diagnosis and treatment.

Implementation of a youth and young adult e-cigarette cessation program within a dental clinic setting : A SToHN feasibility study.

Introduction: While significant progress has been made to decrease tobacco smoking among youth and young adults, e-cigarettes threaten to reverse the progress. The purpose of this study was to test the feasibility of the ReACH Assessment of Knowledge for E-Cigarettes (RAKE) e-cigarette cessation program targeting youth and young adults in Texas. Methods: Seven dental practitioners and 12 patients participated in this pilot study. Patients aged 15 to 29 who reported current e-cigarette use were recruited by their dental practitioner. All participants completed pre-and post-assessments-practitioners receiving the RAKE training and patients the RAKE cessation intervention. Descriptive statistics were calculated. Results: After RAKE training, all practitioners reported the RAKE cessation program as useful and an important part of patient care. In addition, after completing the program (5A's), 67% (n=9) patients reported that the program was helpful, and 100% (n=12) would recommend the program to other ENDS users. Conclusions: Practitioners and patients enhanced their knowledge of e-cigarettes and their harm to health. In addition, practitioners demonstrated their ability to implement the RAKE cessation program within the practice, and patients approved of the use of the program. This study illustrated the feasibility and acceptability of conducting an e-cigarette cessation study in dental practices and a critical need to develop and disseminate the program to young patients.

[Analysis on disease burden of stroke in China and the regions with different sociodemographic index from 1990 to 2017].

Objective: To examine the trend of stroke disease burden and its main risk-attributable factors in China and regions with different Socio-Demographic Index (SDI) from 1990 to 2017. Methods: With 2017 Global Burden of Disease (GBD) data, years lived with disability (YLDs), years of life lost (YLLs) and disability-adjusted of life years (DALYs) were applied to describe the disease burden and major risk factors of stroke in China and different SDI regions from 1990 to 2017, and to analyze the changing trend of the disease burden and major risk factors of stroke. Results: From 1990 to 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China showed an increasing trend and the rate of change was 126.5%, 14.6%, and 24.4%, respectively. In 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China were 502.6 per 100 000, 2 633.1 per 100 000 and 3 135.7 per 100 000, respectively. Among them, the YLD crude rate, YLL crude rate, and DALY crude rate of stroke were the highest in the ≥70 age group, which were 2 617.2 per 100 000, 16 789.4 per 100 000 and 19 406.6 per 100 000, respectively. The YLD crude rate in male was 475.5 per 100 000, which was slightly lower than that of female (530.9 per 100 000), while the DALY crude rate and YLL crude rate for stroke were 3 657.1 per 100 000 and 3 181.7 per 100 000, respectively, which were significantly higher than that of female (2 591.8 per 100 000 and 2 060.9 per 100 000). Compared with regions with different SDI, the age standardized YLD rate, the age standardized YLL rate, the age standardized DALY rate in China were all at a high level. Among them, the age-standardized YLD rate increased from 286.2 per 100 000 to 374.5 per 100 000, with a rate of change of 30.9%; the age-standardized YLL rate decreased from 3 215.6 per 100 000 to 1 967.8 per 100 000, with a rate of change of -38.8%; the age-standardized DALY rate increased from 3 501.8 per 100 000 to 2 342.3 per 100 000, with a rate of change of -33.1%. The top five risk factors for stroke in China were hypertension, excessive sodium intake, insufficient fruit intake, insufficient cereal intake, and smoking in 1990 and 2017. High Body-Mass Index and Alcohol Use's rankings rose from the 9th and 10th in 1990 to the 6th and 7th in 2017, respectively. Conclusion: The burden of stroke disease in China is at a high level, and hypertension is the primary risk factor.

Research Progress on Pathological Fibrosis of Sinoatrial Node.

ABSTRACT: Human heart rhythm is mainly regulated and controlled by the sinoatrial node. Fibrosis plays an important regulating role in adjusting the structural and functional integrity of the sinoatrial node pacemaker complex. In physiological state, the fibrosis degree of sinoatrial node is negatively correlated with heart rate, positively correlated with age and heart size, and can maintain a relatively stable heart rate. Pathological fibrosis of sinoatrial node can induce various types of arrhythmias which can result in sudden death. Determination of the mechanisms related to sinoatrial node pathological fibrosis could provide a target for clinical treatment of sinoatrial node fibrosis and diagnosis basis for forensic pathologists. This paper reviews the main mechanism of sinoatrial node pathological fibrosis, including abnormal activation of cardiac fibroblast cells in sinoatrial node, hyperplasia of epicardial adipose tissue, calcium clock disorder, artery stenosis, etc., introduces the test methods, diagnostic criteria as well as its role in sudden cardiac death and discusses the potential application, to provide reference for relevant research and application.

Inter-relationship of risk factors and pathways associated with chronic kidney disease in patients with type 2 diabetes mellitus: a structural equation modelling analysis.

OBJECTIVES: Diabetes mellitus is the most common cause of chronic kidney disease (CKD); however, the inter-relationships and pathogenetic mechanisms among risk factors are still largely unknown. Structural equation modelling (SEM) was applied to test a hypothesis of causal pathways related to CKD in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 3395 patients with T2DM were enrolled in this study. A hypothesised SEM was applied to assess associations among demographic data, diabetic self-management behaviours, diabetes control, lifestyle, psycho-social, chronic inflammation factors, anthropometric and metabolic variables simultaneously and the risk of CKD. RESULTS: Demographic data (including education, marital status and mini-mental state examination score) (-0.075), white blood cell count (0.084), high blood pressure (0.144), World Health Organisation (WHO) 5 well-being index (-0.082), diabetes control (0.099), triglyceride (0.091) and uric acid (0.282) levels had direct effects on the risk of CKD. The final model could explain 26% of the variability in baseline CKD status. In addition, the same direct and specific indirect factors at baseline CKD status analysis contributed to the risk of CKD at the 12-month follow-up. The final model could explain 31% of the variability in the risk of CKD at the 12-month follow-up. CONCLUSIONS: This study investigates associations between factors obtained from real-world daily practice and CKD status simultaneously and delineates the potential pathways and inter-relationships of the risk factors that contribute to the development of CKD in patients with T2DM.

[The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis].

Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.

[Trends of burden on ischemic heart disease and epidemiological transition of related risk factors in China, 1990-2017].

Objective: To examine the trend of burden on ischemic heart disease (IHD) and epidemiological transition on related risk factors among the Chinese population from 1990 to 2017. Methods: Based on open access data from the Global Burden of Disease (GBD) 2017 Study, we used years of life lost (YLD), years lived with disability (YLL), and disability-adjusted of life years (DALY) to describe the changes of IHD burden stratified by different sex and age groups from 1990 to 2017. We applied population-attributable faction (PAF) to analyze the burden attributable to risk factors and epidemiological transition. Results: In 2017, rates on YLD, YLL, and DALY for IHD were 74.2/100 000, 2 459.6/100 000, and 2 523.1/100 000, respectively. DALY rate and YLL rate for IHD in males were invariably higher than those in females except for YLD rate in females. 24 modifiable risk factors were causally associated with IHD. The top five risk factors that influencing DALYs, PAF, and DALY rate in 2017 appeared as: high blood pressure (16.429 million person years, 54.6%, 1 163.1/100 000), high LDL cholesterol (13 941 million person years, 46.3%, 987.0/100 000), diet high in sodium (10.900 million person years, 36.2%, 771.1/100 000), smoking (8.647 million person years, 28.7%, 612.2/100 000), and low-nut diet (7.452 million person years, 24.8%, 527.6/100 000). DALY rate for IHD showed an increase of 90.9%, from 1 116.4/100 000 in 1990 to 2 131.0/100 000 in 2017. Compared with 1990, the YLD rate experienced an evident increase in those aged 15-49 and over 70, in 2017. Annual average growth rate of YLD rate was higher in the ≥70 age group, between 2007 and 2017 (0.4%) than that between 1990 and 2007 (0.2%). The annual average increasing rates of both YLL and DALY were much lower from 2007 to 2017 (0.6%, 0.6%) than those from 1990 to 2007 (1.3%, 1.2%). From 1990 to 2017, DALYs attributed to meaty food (929.7%), beverages with high sugar content (822.7%), and high body-mass index (327.3%) experienced the highest increase. The largest increase in PAF occurred for beverages with high sugar content (400.0%). DALY rates increased for the 8 risk factors whereas decreased on the 7 risk factors, in consecutive rankings between 2007 and 2017. Conclusions: Despite the fact that burden on IHD-caused premature death had been reducing, related disabilities remain challenging with IHD the leading cause of burden, particularly in the ≥70 year-olds. Higher IHD burden from premature death was seen in males but disability appeared higher in females. It is significantly important to strengthen programs on prevention and control for hypertension including reducing modifiable risk factors such as smoking, unreasonable diet habits.

[Platelet derived growth factor-BB regulates phenotype transformation of pulmonary artery smooth muscle cells via SIRT3 affecting glycolytic pathway].

Objective: To investigate whether platelet-derived growth factor-BB (PDGF-BB) can regulate phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) via SIRT3 affecting glycolytic pathway. Methods: The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into 3 groups by using 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway: normal control group, PDGF-BB group(30 ng/ml) and PDGF-BB (30 ng/ml)+2-DG (10 mmol/L) group. In lentivirus-mediated overexpression assay, cells were divided into control group, PDGF-BB group(30 ng/ml), PDGF-BB+deacetylase sirtuin-3 (SIRT3) overexpression group and PDGF-BB+empty vector group. The expression levels of phenotype related index such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), calponin, vimentin were detected by qRT-PCR and Western blot. Meanwhile, the expression of α-SMA was detected by cellular immunofluorescence staining. EDU staining was used to detect the proliferation of PASMCs. The expression of SIRT3 was detected by Western blot. The expressions of glucose transporter 1 and aerobic glycolytic enzymes were detected by qRT-PCR and Western blot in lentivirus-mediated overexpression assay. Results: (1) PDGF-BB affects PASMCs phenotypic transformation through glycolytic pathway: compared with normal control group, PDGF-BB significantly decreased the expressions of contractile phenotype markers such as α-SMA, SM-MHC, calponin mRNA and protein (all P<0.05), but it increased the expressions of the synthetic phenotype marker vimentin mRNA and protein (both P<0.05). Cellular immunofluorescence assay showed that PDGF-BB significantly decreased the number of α-SMA positive cells, while 2-DG reversed the process. (2) PDGF-BB promoted cell proliferation through glycolytic pathway: the proliferation of PASMCs was significantly higher in PDGF-BB group than in control group (P<0.05), and which could be significantly reduced by 2-DG (P<0.05). (3) PDGF-BB inhibited the expression of SIRT3 protein in PASMCs: the expression of SIRT3 protein in PDGF-BB group was lower than that in control group (P<0.05). (4) PDGF-BB affected glycolytic pathway through SIRT3:compared with the control group, PDGF-BB significantly increased the expression levels of glucose transporter 1 (Glut1), hexokinase 2 (HK2) and 6-phosphfructo-2-kinase 3 (PFKFB3) mRNA (all P<0.05), which was reserved by over-expression of SIRT3. There were no significant difference in mRNA expression levels between PDGF-BB group and PDGF-BB+empty vector group (P>0.05).Compared with the control group, PDGF-BB significantly increased the expression levels of Glut1, HK2 and PFKFB3 protein(all P<0.05), which was reserved by over-expression of SIRT3. There were no significant differences in protein expression levels between PDGF-BB group and PDGF-BB+empty vector group (all P>0.05). Conclusion: PDGF-BB regulates phenotypic transformation of PASMCs via SIRT3 affecting glycolytic pathway.

An Individualized Low-Intensity Walking Clinic Leads to Improvement in Frailty Characteristics in Older Veterans.

BACKGROUND: Sedentary lifestyle leads to worse health outcomes with aging, including frailty. Older adults can benefit from regular physical activity, but exercise promotion in the clinical setting is challenging. OBJECTIVES: The objective of this clinical demonstration project was to implement a Geriatric Walking Clinic for older adults and determine whether this clinical program can lead to improvements in characteristics of frailty. DESIGN: This was a clinical demonstration project/quality improvement project. SETTING: Outpatient geriatrics clinic at the South Texas Veterans Health Care System (STVHCS). PARTICIPANTS: Older Veterans, aged ≥60 years. INTERVENTION: A 6-week structured walking program, delivered by a registered nurse and geriatrician. Patients received a pedometer and a comprehensive safety evaluation at an initial face-to-face visit. They were subsequently followed with weekly phone calls and participated in a final face-to-face follow-up visit at 6 weeks. MEASUREMENTS: Grip strength (handheld dynamometer), gait speed (10-ft walk), Timed Up and Go (TUG), and body mass index (BMI) were assessed at baseline and follow-up. Frailty status for gait speed was assessed using Fried criteria. RESULTS: One hundred eighty five patients completed the program (mean age: 68.4 ±7 years, 88% male). Improvements from baseline to follow-up were observed in average steps/day, gait speed, TUG, and BMI. Improvement in gait speed (1.13 ±0.20 vs. 1.24 ± 0.23 meter/second, p<0.0001) resulted in reduced odds of meeting frailty criteria for slow gait at follow-up compared to the baseline examination (odds ratio = 0.31, 95% confidence interval: 0.13-0.72, p = 0.01). CONCLUSIONS: Our findings demonstrate that a short duration, low-intensity walking intervention improves gait speed and TUG. This new clinical model may be useful for the promotion of physical activity, and for the prevention or amelioration of frailty characteristics in older adults.

Targeted regulation of miR-17-5p on TMOD1 promotes the development of cardia cancer.

OBJECTIVE: Cardia cancer is a common type of gastric cancer. Most clinical prevention and prognosis focus on surgical resection, but the efficacy is not satisfactory. Studying the molecular mechanism of pathogenesis of cardia cancer helps us intervene in prognosis and treatment. MATERIALS AND METHODS: a total of 134 normal cases related to cardia cancer and 62 cases of cardia cancer samples from the Gene Expression Omnibus (GEO) database were collected. A series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, regulator prediction, and (Protein-protein interaction) PPI analysis validation were performed. RESULTS: Differential analysis highlighted 10882 differential genes (p<0.05). Weighted gene co-expression network analysis indicated 6 functional disorder modules. TMOD1, JAM2, SPARC, ST18, NOS1 were key genes of each module. Enrichment analysis showed the dysfunctional module genes were mainly related to the proteinaceous extracellular matrix and neuroactive ligand-receptor interaction. Pivotal analysis of ncRNA demonstrated miR-17-5p significantly regulates modular genes including m1, m3, and m5. Target genes were backtracked according to the key regulators. Then, the Module_target gene_ncRNA interaction network diagram was constructed. The network shows m1 has the strongest regulation effect in the network. PPI showed that the core gene TMOD1 (Tropomodulin1) of m1 was at TOP10 in the algorithm. In other words, PPI indicated the importance of TMOD1 in the interaction network. CONCLUSIONS: We believe that targeted regulation of miR-17-5p on TMOD1 gene affects the neuroactive ligand-receptor interaction pathway, and it promotes proliferation and apoptosis of cardia cancer cells.

Short communication: Effects of dietary addition of N-carbamoylglutamate on milk composition in mid-lactating dairy cows.

The present study was conducted to investigate the effect of N-carbamoylglutamate (NCG) on milk production and composition in mid-lactating Holstein dairy cows. Sixty multiparous cows with a mean body weight of 669 kg (standard deviation = 71) and 176 days in milk (standard deviation = 55) were blocked based on parity and milk production and randomly assigned into 4 treatments, a basal diet supplemented with 0, 10, 20, or 40 g of NCG/d per cow. Milk yield and composition were recorded weekly, whereas dry matter intake and plasma variables were determined every 2 wk. The results showed that the addition of NCG had no effect on the dry matter intake and milk yield of the cows. Milk fat content and yield increased linearly with NCG addition. The contents of milk protein and total solid also increased linearly in the cows fed NCG, whereas the yield of protein was not affected by the treatments. Conversely, dietary addition of NCG increased the plasma nitric oxide content in a quadratic manner. Moreover, addition of NCG linearly increased the plasma Arg content. Overall, the results indicate that dietary NCG addition increased the milk protein and fat contents, which improved the milk quality of lactating dairy cows.

The interaction between smoking and CYP1A1 MspI polymorphism on lung cancer: a meta-analysis in the Chinese population.

Many studies have examined the interaction between CYP1A1 MspI gene polymorphism and smoking for the risk of lung cancer risk in Chinese, but their results have been inconsistent. Therefore, a meta-analysis was performed to ascertain this issue. PubMed, Springer Link, Ovid and other Chinese databases were searched to include all the relevant studies. Smoking status was categorised as 'smokers' and 'non-smokers.' The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random effect model. Subgroup analyses according to ethnicity, source of control and geographical location were also conducted. This meta-analysis identified 13 studies containing 2248 lung cases and 3079 controls. Overall, a significant association between lung cancer and the variants of CYP1A1 MspI was found among smokers (type B and type C combined vs. type A: OR = 1.89, 95% CI = 1.15-3.11, P = 0.000 for heterogeneity), whereas not found among non-smokers. Similar to the overall results, stratified analyses showed that the increased risk of lung cancer was observed in population-based studies and north China among smokers (OR = 1.65, 95%CI = 1.03-2.66; OR = 2.00, 95% CI = 1.14-3.53). Our meta-analysis showed that there was an interaction between the CYP1A1 MspI and smoking on the risk of lung cancer in the Chinese population.

[In vivo and in vitro effects of CD137 stimulation on vascular calcification in high fat diet fed ApoE-/- mice].

Objective: To investigate the effect and related mechanism of CD137 stimulation on aortic atherosclerotic plaque calcification in high fat diet fed ApoE-/- mice and on calcification of vascular smooth muscle cells (VSMCs). Methods: (1) ApoE-/- mice fed with high fat diet were randomly divided into 3 groups: CD137 activated group (treated by 200 µg CD137 agonist i. p. once per week for 6 weeks, n=5); CD137 inhibited group (anti-CD137 group: 200 µg anti-CD137 antibody + 200 µg CD137 agonist, i. p., once per week for 6 weeks, n=5) and control group (n=5). Von kossa staining was used to observe the calcification of the aortic plaque and VSMCs. Immunohistochemistry was used to observe the expression of BMP-2 and Runx2 which are known mediators of osteogenic differentiation. (2) The mouse aortic VSMCs were obtained by Patch-attaching method. The calcium content was measured by Methylthymol Blue complexone method. The mRNA expressions of bone morphogenetic protein 2 (BMP-2) and Runx2 were measured by real-time fluorescent quantitative PCR (RT-PCR). The protein levels of BMP-2, Runx2 of the VSMCs were determined by Western blot. Results: (1) In vivo, the plaque calcified area in ApoE-/- mice was significantly larger in CD137-agonist group than that in control group ((1.75±0.33)×104 µm2 vs. (0.23±0.07)×104 µm2,P<0.01), and this effect was significantly reduced by cotreatment with CD137-antagonist ((0.83±0.30)×104 µm2 vs. (1.75 ±0.33)×104 µm2,P<0.05). The levels of BMP-2 and Runx2 were all significantly upregulated in CD137-agonist group than in control group (both P<0.01), again, this effect was blocked by cotreatment with CD137-antagonist (P<0.05). (2) Consistent with the in vivo results, VSMCs calcification was also more serious in CD137-agonist group than in control group, which could be significantly attenuated by cotreatment with CD137-antagonist. In VSMCs, calcium content level in CD137-agonist group was higher than in control group ((0.001 3±0.000 2) mmol/mg protein vs. (0.000 7±0.000 1) mmol/mg protein, P<0.01), which could be significantly reduced by co-treatment with CD137-antagonist ((0.000 9±0.000 2) mmol/mg protein vs. (0.001 3±0.000 2) mmol/mg protein, P<0.01). The mRNA and protein levels of BMP-2 and Runx2 were significantly upregulated in CD137-agonist group compared with the control group (P<0.05), which could be significantly down-regulated by cotreatment with CD-137 antagonist (P<0.05). Conclusion: CD137 activation can promote vascular calcification in high fat diet fed ApoE-/- mice both in vivo and in vitro.

A first-principles study of the diffusion coefficients of alloying elements in dilute α-Ti alloys.

Using first-principles calculations accompanied by the transition state theory and an 8-frequency model, we present a comprehensive investigation of the diffusion coefficients of substitutional alloying elements X in dilute α-Ti alloys, where X denotes Al, V, Nb, Ta, Mo, Zr, and Sn. The alloying elements Mo and Al exhibit a maximum and a minimum diffusion rate in dilute α-Ti alloys, respectively. It is found that the nearest-neighbor solute-vacancy binding energies and activation energies are roughly inversely proportional to the volume changes induced by solute atoms. There are two exceptions to this trend: Al and Mo. Besides the physical effect (i.e., solute size), two other key factors governing solute diffusion in dilute α-Ti are clarified: the chemical bonding characteristics and vibrational features of X-Ti pairs. It verifies that the ultrafast diffusivity of Mo arises from the interactions with Ti atoms by metallic bonds and its low-frequency contributions to lattice vibration, while the more covalent bonding nature and the high-frequency contributions to the lattice vibration of Al lead to its ultraslow diffusivity. In addition, the correlation effects of diffusion coefficients are non-negligible for the large solutes Ta, Nb, and Zr, in which the direct solute-vacancy migration barriers are much smaller than the solvent-vacancy migration barriers.

Abnormal correlation between phase transformation and cooling rate for pure metals.

This work aims to achieve deep insight into the phenomenon of phase transformation upon rapid cooling in metal systems and reveal the physical meaning of scatter in the time taken to reach crystallization. The total number of pure metals considered in this work accounts for 14. Taking pure copper as an example, the correlation between phase selection of crystal or glass and cooling rate was investigated using molecular dynamic simulations. The obtained results demonstrate that there exists a cooling rate region of 6.3 × 10(11)-16.6 × 10(11) K/s, in which crystalline fractions largely fluctuate along with cooling rates. Glass transformation in this cooling rate region is determined by atomic structure fluctuation, which is controlled by thermodynamic factors. According to the feature of bond-orientation order at different cooling rates, we propose two mechanisms of glass formation: (i) kinetic retardation of atom rearrangement or structural relaxation at a high cooling rate; and (ii) competition of icosahedral order against crystal order near the critical cooling rate.

[Meta-analysis on related risk factors regarding lung cancer in non-smoking Chinese women].

OBJECTIVE: To explore the risk factors of lung cancer in non-smoking Chinese women and to provide evidence for lung cancer prevention and control. METHODS: Information was collected on case-control studies published in the journals, both nationally and internationally from January, 1995 to November, 2014 that reported correlations between lung cancer and risk factors. Pooled odds ratio (OR) and 95% confidence interval (CI) of risk factors on lung cancer in non-smoking Chinese women were calculated, using the Meta-analysis method, with sensitivity and publication bias tested. RESULTS: Information on 24 case-control studies was selected including 11 946 cumulative cases and 12 596 controls. Pooled ORs (95% CI) were shown as: history of lung diseases 1.89 (1.57, 2.27), history of tuberculosis 1.86 (1.53, 2.27), history of chronic bronchitis 1.51 (1.04, 2.19), family history of cancers 2.02 (1.67, 2.44), family history of lung cancers 2.45 (1.80, 3.34), passive smoking (at workplace in adult period 1.47 (1.28, 1.69), at home in adulthood 1.22 (1.09, 1.36), in all life's time 1.52 (1.29, 1.79), kitchen smog while cooking 2.21 (1.27, 2.96), position of kitchen 1.76 (1.48, 2.09), and frequency of deep frying per week 2.24 (1.61, 3.12) etc. respectively. CONCLUSION: Major risk factors related to lung cancer in non-smoking Chinese women would include lung diseases, family history of cancers, and passive smoking (tobacco smog and cooking smog). Particularly, the combination of family history and the degree of cooking presented stronger correlation effects, indicating that genetic and environmental factors jointly played an important role in the development of lung cancer.

[CD137-CD137L signaling promotes angiogenesis in atherosclerosis plaque of mice through activating nuclear factor of activated T cells c1].

Objective: To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1 (NFATc1). Methods: Apolipoprotein E knock out mice were divided into the following groups: control group (n=5), CD137 activated group(n=5)and CD137 inhibited group (n=5). Immunohistochemistry was performed to detect the expression of CD31 in aortic plaque. Endothelial cells (bEnd.3) were purchased from ATCC and divided into the following groups: control group, IgG isotype control group, CD137 activated group and CD137 inhibited group. Western blot was used to determine total protein and nucleoprotein expression of NFATc1. The expression level of CD137 protein on the surface of endothelial cells was detected by flow cytometry(FCM) and CD137 protein of lysate of endothelial cells was detected by enzyme-linked immunosorbent assay (ELISA). Transwell assay was used to observe the migration ability of endothelial cells.Matrigel tube formation ability of endothelial cells were tested in the following groups: control group, CD137 activated group, silent NFATc1 + CD137 activated group, CD137 inhibited group, and over expressed NFATc1+ CD137 inhibited group. Results: (1) In vivo, the expression level of CD31 was significantly higher in the aortic plaque of CD137 activated group than in control group(1 191±187 vs. 115±30, P<0.05), while which was significantly downregulated in CD137 inhibited group(450±92, P<0.05). (2) The level of nucleoprotein(3.07±0.03 vs. 1.00±0.00, P<0.05) and total protein(2.18±0.30 vs. 1.00±0.00, P<0.05) of NFATc1 were significantly higher in CD137 activated group than in IgG isotype control group. The level of nucleoprotein(0.82±0.04) and total protein(0.84 ± 0.09) of NFATc1 were significantly lower in CD137 inhibited group than in CD137 activated group(both P<0.05). (3) FCM results showed that the fluorescence intensity of CD137 on the cell membrane was significantly higher in endothelial cells stimulated by TNF-α than in normal endothelial cells(5 163±329 vs. 1 660±162, P<0.05). (4) ELISA examination showed that the level of CD137 protein was significantly higher in endothelial cells stimulated by TNF-α than in normal endothelial cells ((573.4±23.7)pg/mg vs.(69.5±16.7)pg/mg, P<0.05). (5) Migration cell number was remarkably higher in CD137 activated group than in IgG isotype control group(1.19±0.13 vs. 1.00±0.00, P<0.05) and significantly lower in CD137 inhibited group(0.82±0.06)than in control group (P<0.05). (6) Values of the formation of the tube length ((5.76±0.18)mm vs. (4.21±0.11)mm, P<0.05) and branch number (29.38±1.28 vs. 21.13±0.96, P<0.05) were both significantly higher in CD137 activated group than in the control group. The formation of the tube length ((1.90±0.11)mm) and branch number(8.91±0.72)were significantly lower in silent NFATc1 + CD137 activated group than in the CD137 activated group (both P<0.05). The formation of the tube length((1.28±0.34)mm) and branch number(5.07±0.35)were also significantly decreased in the CD137 inhibited group compared with the CD137 activated group (both P<0.05). Compared with the CD137 inhibited group, the formation of the tube length((4.82±0.09)mm) and branch number(24.44±1.05) in the over expressed NFATc1+ CD137 inhibited group was increased (both P<0.05). Conclusion: CD137 can promote the angiogenesis in atherosclerosis plaque by activating NFATc1.