BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective:To describe the current status of smoking among Chinese people aged 15 and above and analyze its epidemic evolution.Methods:A stratified multi-phased randomized cluster sampling design of the Global Adult Tobacco Survey was used. The cross-sectional survey was conducted from July to December 2018, covering 200 districts/counties in 31 provinces of China. Field data was collected through in-house face-to-face interviews by trained investigators using a tablet computer. 19 376 individual questionnaires were completed, with an overall response rate of 91.50%. The data were weighted for complex sampling and analyzed with SAS 9.4.Results:In 2018, the current smoking prevalence of adults aged 15 and above was 26.59%, with that higher among males (50.47%) than among females (2.07%) and higher among those in rural (28.87%) than among those in urban areas (25.05%). The quitting rate was 20.10%, with a higher rate among females (30.22%) than males (19.64%). However, there was no significant difference between rural and urban areas ( P=0.864). Compared with the previous data, the smoking rate tends to drop, with a substantial decrease among the 25-44 age groups and 45-64 age groups. The most significant decline occurs among those with higher education (Junior college and above). In addition, in 2018, current daily smokers aged 15 and above in China started to smoke daily at an average age of 20.95 years old. For current smokers, 16.00 cigarettes were consumed each day on average. Conclusion:Although the current smoking prevalence among the Chinese population aged 15 and above tends to decrease, the decreasing speed is too slow to achieve the target set in the Healthy China Action (2019-2030). Consequently, much more effective efforts to control tobacco need to be enforced.

Objective:To describe the current situation on quit intention and quit attempts among current smokers aged 15 years and above in China and explore the main factors affecting their smoking cessation behaviors.Methods:The subjects were people aged 15 years and above in China. A stratified multi-phased randomized cluster sampling method was used. The survey covered 200 districts/counties in 31 provinces (autonomous regions and municipalities directly under the central government), including 19 376 people under investigation. The data were weighted with SAS 9.4 for complex sampling analysis, and the frequency and weighted component ratio were used for description. The influencing factors were studied using the Rao Scott χ2 test and unconditional multivariate logistic regression. Results:Among current smokers, 6.63% reported that they planned to quit smoking in the next month, 5.44% for men and 8.49% for women. 17.96% of the current smokers made quit attempts in the past 12 months, with 17.80% men and 22.15% women. People who smoke occasionally ( OR=3.42, 95% CI: 2.09-5.59) made quit attempts in the past ( OR=4.91, 95% CI: 0.33-0.52) and knew that smoking would lead to three diseases ( OR=2.24, 95% CI: 1.48-3.40) had higher quit intention. People who occasionally smoke ( OR=1.68, 95% CI: 1.20-2.34) received smoking cessation suggestions from medical staff ( OR=1.96, 95% CI: 1.62-2.37), were a ware of that smoking causes three diseases ( OR=1.63, 95% CI: 1.32-2.02) and had smoking prohibition regulations in indoor areas of their homes, had a higher rate of quit attempts. Conclusion:Providing effective smoking cessation intervention services and creating a supportive tobacco control environment are significant in promoting smoking cessation behavior.

Objective:To investigate secondhand smoke (SHS) exposure among non-current smokers aged 15 and over and its influencing factors in China in 2010 and 2018.Methods:The 2010 and 2018 China Adult Tobacco Surveys used multistage stratified cluster random sampling methods to obtain national representative samples across 31 provinces (autonomous regions and municipalities) in China. This study selected non-current smokers aged 15 and over as the research subjects to describe the general demographic characteristics, perceptions of SHS hazards, attitudes towards smoking bans in indoor areas in public places, and SHS exposure and the smoking restriction regulations in different places. The Rao-Scott χ2 test was used to compare the rates, and the unconditional logistic regression was used to analyze the influencing factors of SHS exposure. All the subjects in the analysis were weighted based on a complex sampling design. Results:Among non-current smokers aged 15 and over, from 2010 to 2018, the percentage of indoor smokers had decreased from 84.7% to 71.9%. The rates of people who saw smoking in various places declined with a statistically significant difference ( P<0.001). The exposure to SHS for females, people aged 45-64, teachers, medical staff, workers in enterprises, businesses, waiters, and people who live in rural and central areas declined. The differences were statistically significant ( P<0.05). In 2018, the percentage of SHS exposure for those who reported a comprehensive smoking ban in households or allowed smoking in certain areas was lower than for those who reported allowed or without a smoking ban. Among those aged 25-44, SHS exposure for those who reported complete smoking prohibition in workplaces was lower than those who reported allowed or without smoking prohibition ( OR=0.65, 95% CI: 0.49-0.87). The proportion of SHS exposure for those who believe that smoking should not be allowed in indoor areas of 0-5 public places is higher than that smoking should not be allowed in the indoor spaces of 8 public places ( OR=2.13, 95% CI: 1.35-3.36). Among people aged 45-64, the proportions of SHS exposure for teachers ( OR=0.37, 95% CI: 0.17-0.78) and medical staff ( OR=0.35, 95% CI: 0.16-0.76) and staff working in agriculture, forestry, animal husbandry, fishery, and water conservancy were lower than governmental staff ( OR=0.49, 95% CI: 0.29-0.84). Conclusions:Data from the decreased exposure of Chinese non-current smokers aged 15 and over to SHS suggests the initial achievement through constructing a smoke-free environment, but continued efforts are needed. It is necessary to actively advocate for smoke-free families, strengthen publicity and education on the hazards of tobacco and SHS, and improve the skills of non-smokers in rejecting SHS exposure.

Objective:To investigate the exposure to tobacco advertisements and promotions among Chinese adults aged 15 and above, identify the publicity channels and forms of tobacco advertising and promotion in 2010 and 2018, and implicate further tobacco control measures in China.Methods:A multistage, stratified, randomized cluster sampling design was used in 2010 and 2018 China Adult Tobacco Survey, with national representativeness. 13 354 and 19 376 permanent residents were selected in the 2010 and 2018 surveys. SAS 9.4 software was applied for data analysis, and all the data were weighted based on a complex sampling design. Rao Scott χ2 test was used for group comparison of a single factor. Results:In 2010 and 2018, 19.61% and 18.14% of the survey respondents did see tobacco advertising and promotion. From 2010 to 2018, there was no significant change in the situation of tobacco advertisements and promotions. Among those who had gone to a cigarette shop, the proportion of seeing tobacco advertisements increased from 29.28% in 2010 to 43.28% in 2018. Among those who had seen tobacco advertisements on TV, the rate fell from 50.93% in 2010 to 28.58% in 2018. Among those who had gone to movie theaters, the proportion of seeing tobacco advertisements increased from 2.17% in 2010 to 9.89% in 2018. Among those who had used the Internet, the proportion of seeing tobacco advertisements online rose from 19.20% in 2010 to 42.30% in 2018. In terms of tobacco promotion, the percentages of people who had seen tobacco promotions, cigarette price discounts, cigarette discount coupons, gifts, and other preferential activities in various places in the past 30 days were 4.99% vs. 9.30%, 0.78% vs. 4.09%, 0.04% vs. 0.33% and 0.98% vs. 3.33% in 2010 and 2018, respectively ( P<0.001). Conclusions:Tobacco advertising and promotion are still prevalent in China, with no significant change in 2010 and 2018. Tobacco advertising and promotion have been with the constant changes and development of media platforms. It is necessary to improve the implementation of relevant policies, comprehensively ban tobacco advertisements and promotions, and strengthen the supervision of ads and promotions.

Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.

Objective An optimal radiation dose was made research on tumor cells to develop effective tumor fusion vaccines. Methods We used the RS 2000 biological X-ray radiation instrument to produce different dose of X-rays.Mouse liver cancer cells line,BNL 1ME a.7R.1(MEAR),was used for experiment.The RS 2000 biological X-ray radiation was applied to create different tumor cell clones,which could help us to study the rela-tionship between irradiation dose and tumor cells′proliferation activity.Furthermore,the fusion cells′anti-tumor ef-fect was examined by flow cytometry. Results High-dose radiation would induce the lower proliferation of cancer cells than low-dose irradiation do.Conclusions During the preparation of fusion vaccines,irradiation dose should be considered as a factor that would influence the tumor cells′ proliferation activity. When the dose of irradiation was appropriate,we could make safe and efficient integration cell vaccines.

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats .Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking ( health canada method , HCM) manner , and those with tar of 11 mg were also smoked in international standard ( ISO) smoking manner .Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure .After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro -inflammatory cytokines IL-1βand TNF-α.The right lungs were subjected to histological examination and determination of myeloperoxidase ( MPO ) and superoxide dismutase (SOD) activities and glutathione , reactive oxygen species (ROS) and malondialdehyde (MDA) levels.Results:In both HCM and ISO manners , the degree of lung injury was closely related to the tar content of cigarettes , and significant decrease in the body weight of rats was observed after smoking for one week .In a HCM manner , smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages , lymphocytes and neutrophils into lungs , significant increase in IL-1βand TNF-αlevels and MPO activities , and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels ( all P <0.05 ) .Smoking with cigarette of 5 mg tar led to moderate increase in IL-1βand TNF-αlevels, and MPO activities (all P<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels ( all P<0.05).However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1βand TNF-αlevels.Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes .

α-Amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptor, a subtype of ionotropic glutamate receptors widely distributed in the central nervous system, mediates the fast excitatory neurotransmission. Meanwhile more and more evidence indicates that AMPA receptor plays an important role in synaptic plasticity as well as central sensitization, and it also has close relationships with nervous system diseases. Over stimulation of AMPA receptor would produce excitotoxicity, leading to neuronal damage and finally resulting in a multitude of nervous system diseases, such as epilepsy, amyotrophic lateral scelerosis,Parkinson′s dis-ease. Competitive AMPA receptor antagonists that downregulate AMPA receptor′s function are of great importance in the prevention and treatment of nervous system diseases. This article reviews the research advances of competitive AMPA receptor antagonists.