Objective:To investigate the expression level of methyltransferase-like 3 (METTL3) in nasopharyngeal carcinoma cells CNE2 and CNE-2R, and to evaluate the effect of METTL3 on cell invasion, metastasis and radiosensitivity.Methods:Real-time reverse transcription PCR and Western blot were used to detect the expression levels of METTL3 in normal nasopharyngeal epithelial cells NP69 and nasopharyngeal carcinoma cells CNE2 and nasopharyngeal carcinoma radioresistant cells CNE-2R cells. METTL3 in CNE2 and CNE-2R cells was silenced by lentivirus-mediated RNA interference technology. The metastasis and invasion abilities of the cells were detected by the scratch assay and Transwell assay. Clonogenic assay and CCK-8 assay were employed to detect the proliferation capacity and viability of cells irradiated with different X-ray doses (0, 2, 4, 6 and 8 Gy). Apoptosis was detected by flow cytometry. Methylated RNA immunoprecipitation (Me-RIP) assay was used to detect the difference in m6A modification level of c-Jun in CNE2 and CNE-2R cells after METTL3 silencing. The transcriptional stability of c-Jun in cells after silencing METTL3 was detected by actinomycin D assay. A nude mouse xenograft model was constructed to detect the effect of METTL3 on the radiosensitivity of nasopharyngeal carcinoma in vivo. Results:Compared with NP69 cells, the expression levels of METTL3 mRNA and protein were significantly increased in CNE2 cells, and the expression level was even higher in CNE-2R cells (all P<0.01). Lentivirus-mediated RNA interference technology was used to construct a stable METTL3-silencing CNE2 and CNE-2R cell lines (both P<0.01). Scratch assay and Transwell assay showed that the metastasis and invasion abilities of CNE2 and CNE-2R cells were decreased significantly after METTL3 silencing (all P<0.05). Clonogenic assay showed that silencing METTL3 significantly reduced the number of colonies and survival fraction of CNE2 and CNE-2R cells after irradiation with different doses of X-rays (all P<0.05). CCK-8 assay showed that the proliferation ability of CNE2 and CNE-2R cells was significantly reduced by silencing METTL3 (all P<0.05). After different doses of irradiation, silencing METTL3 significantly reduced the survival fraction of CNE2 and CNE-2R cells (all P<0.05). The apoptotic rate after METTL3 silencing was higher than that in the control group at the irradiation dose of 0 and 8 Gy (all P<0.05). The Me-RIP assay showed that the m6A modification level of c-Jun in CNE2 and CNE-2R cells was significantly reduced after METTL3 silencing (both P<0.01), and the actinomycin D assay showed that transcriptional stability of c-Jun was reduced. Nude mouse xenograft experiment showed that silencing METTL3 inhibited xenograft proliferation and improved its radiosensitivity. Conclusion:METTL3 is highly expressed in nasopharyngeal carcinoma cells, and METTL3 mediates m6A modification of c-Jun to improve the transcriptional stability of c-Jun and promote the expression of c-Jun, thereby promoting the invasion and metastasis of nasopharyngeal carcinoma cells and reducing their radiosensitivity.

Objective:To investigate the expression level of methyltransferase-like 3 (METTL3) in nasopharyngeal carcinoma cells CNE2 and CNE-2R, and to evaluate the effect of METTL3 on cell invasion, metastasis and radiosensitivity.Methods:Real-time reverse transcription PCR and Western blot were used to detect the expression levels of METTL3 in normal nasopharyngeal epithelial cells NP69 and nasopharyngeal carcinoma cells CNE2 and nasopharyngeal carcinoma radioresistant cells CNE-2R cells. METTL3 in CNE2 and CNE-2R cells was silenced by lentivirus-mediated RNA interference technology. The metastasis and invasion abilities of the cells were detected by the scratch assay and Transwell assay. Clonogenic assay and CCK-8 assay were employed to detect the proliferation capacity and viability of cells irradiated with different X-ray doses (0, 2, 4, 6 and 8 Gy). Apoptosis was detected by flow cytometry. Methylated RNA immunoprecipitation (Me-RIP) assay was used to detect the difference in m6A modification level of c-Jun in CNE2 and CNE-2R cells after METTL3 silencing. The transcriptional stability of c-Jun in cells after silencing METTL3 was detected by actinomycin D assay. A nude mouse xenograft model was constructed to detect the effect of METTL3 on the radiosensitivity of nasopharyngeal carcinoma in vivo. Results:Compared with NP69 cells, the expression levels of METTL3 mRNA and protein were significantly increased in CNE2 cells, and the expression level was even higher in CNE-2R cells (all P<0.01). Lentivirus-mediated RNA interference technology was used to construct a stable METTL3-silencing CNE2 and CNE-2R cell lines (both P<0.01). Scratch assay and Transwell assay showed that the metastasis and invasion abilities of CNE2 and CNE-2R cells were decreased significantly after METTL3 silencing (all P<0.05). Clonogenic assay showed that silencing METTL3 significantly reduced the number of colonies and survival fraction of CNE2 and CNE-2R cells after irradiation with different doses of X-rays (all P<0.05). CCK-8 assay showed that the proliferation ability of CNE2 and CNE-2R cells was significantly reduced by silencing METTL3 (all P<0.05). After different doses of irradiation, silencing METTL3 significantly reduced the survival fraction of CNE2 and CNE-2R cells (all P<0.05). The apoptotic rate after METTL3 silencing was higher than that in the control group at the irradiation dose of 0 and 8 Gy (all P<0.05). The Me-RIP assay showed that the m6A modification level of c-Jun in CNE2 and CNE-2R cells was significantly reduced after METTL3 silencing (both P<0.01), and the actinomycin D assay showed that transcriptional stability of c-Jun was reduced. Nude mouse xenograft experiment showed that silencing METTL3 inhibited xenograft proliferation and improved its radiosensitivity. Conclusion:METTL3 is highly expressed in nasopharyngeal carcinoma cells, and METTL3 mediates m6A modification of c-Jun to improve the transcriptional stability of c-Jun and promote the expression of c-Jun, thereby promoting the invasion and metastasis of nasopharyngeal carcinoma cells and reducing their radiosensitivity.

Abstract Research has shown that occupational stress is closely related to the occurrence and progression of atherosclerosis, with immune dysregulation serving as a mediating factor. Occupational stress triggers immune dysregulation in the body, ultimately leading to atherosclerosis through mechanisms such as the activation of immune cells and inflammatory mediators, endothelial dysfunction, and lipid metabolism disorders. This article reviews the primary mechanisms by which immune dysregulation plays a role in atherosclerosis caused by occupational stress, providing the reference for the prevention and intervention of atherosclerosis.

Objective:To analyze the research status, development trend and frontier hotspots of midwifery education in China in recent 20 years.Methods:Based on the topic of "midwifery education" or "midwifery teaching", this paper searched the periodical literatures from 2001 to 2021 on CNKI database, and used CiteSpace5.7R5 software to analyze them visually and generate knowledge map.Results:A total of 548 Chinese papers were included in this study, and the annual number of published papers showed an overall upward trend. The research field of midwifery education in China formed an obvious core team, and there was few cooperation among core author groups. Health Vocational Education, Chinese Nursing Education and Chinese Higher Medical Education were the top three journals. The six topics with the highest frequency were midwifery specialty, midwifery personnel, midwifery education, practice teaching, delivery mode and teaching mode, forming 10 clusters of midwifery education. In recent three years, the research of midwifery education in China has gradually changed into simulation teaching, flipped classroom, postpartum rehabilitation and so on. Conclusion:The research scope of midwifery education in China is wide and has formed an obvious core team, but the correlation is weak and there is less communication and cooperation among the research teams. The research in the field of high-level midwifery education is insufficient. Midwifery educators and researchers should pay enough attention to carry out in-depth research on relevant aspects.

Objective:To study the trend of menarche age in Han and Mongolian women born from 1951 to 2005 in Mongolian region.Methods:A cross-sectional cluster sampling survey method was adopted, From 2003 to 2019, a retrospective survey was carried out in three banners/counties in Tongliao region on the female population of Han and Mongols nationalities aged 16 to 46 and conducted under standardized survey procedures and quality control standards. The basic data of menarche age of women born between 1951 and 2005 were obtained. The changes and rules were analyzed by taking 1 year, 5 years and 10 years as nodes.Results:Totally 46 and conducted under standardized survey procedures and quality control standards 928 pepole (24 450 Han and 22 478 Mongolian) were recruited, the survey response rate was 96.09% (46 928/48 836). In one-year-period analysis, the menarche age gradually decreased from 1951 to 2005. The mean menarche age of Han and Mongolian women changed from (16.22±0.52) years and (15.86±1.24) years in 1951 to (12.37±1.15) years and (12.33±0.98) years in 2005, respectively. The mean menarche age of Han and Mongolian women decreased 3.85 years and 3.54 years. The trend of the mean menarche age's change showed a significant negative correlation with the years (all P<0.000 1). In five-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.54±1.45) years and (15.53±1.48) years from 1951 to 1955 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.13 years (3.41 months ahead of schedule every 5 years on average) and 3.06 years (3.34 months ahead of schedule every 5 years on average) in Han and Mongolian women respectively. In ten-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.79±0.95) years and (15.53±1.33) years from 1951 to 1960 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.38 years (6.76 months ahead of schedule every 10 years on average) and 3.06 years (6.12 months ahead of schedule every 10 years on average) in Han and Mongolian women respectively. During the 15 years from 1951 to 1965, 1966 to 1970, 1971 to 1990, and 1991 to 2000, they were concentrated at the ages of 15-16, 14-15, 13-14, and 12-13, respectively. The proportion of women at 11 years, 12 years and 13 years menarche age were 26.79% (457/1 706), 73.27% (1 250/1 706), and 92.85% (1 584/1 706) during 2001—2005 in Han women, while the proportion were 23.25% (653/2 809), 62.01% (1 742/2 809), and 90.14% (2 532/2 809) in Mongolian women. Conclusion:The menarche age decreased in Han and Mongolian women from 1951 to 2005, and the ethnic groups tended to be the same. It is recommended to start adolescent education at the age of 8-9 years and pay attention to the changing pattern of early onset of menarche.

Objective:To study the trend of menarche age in Han and Mongolian women born from 1951 to 2005 in Mongolian region.Methods:A cross-sectional cluster sampling survey method was adopted, From 2003 to 2019, a retrospective survey was carried out in three banners/counties in Tongliao region on the female population of Han and Mongols nationalities aged 16 to 46 and conducted under standardized survey procedures and quality control standards. The basic data of menarche age of women born between 1951 and 2005 were obtained. The changes and rules were analyzed by taking 1 year, 5 years and 10 years as nodes.Results:Totally 46 and conducted under standardized survey procedures and quality control standards 928 pepole (24 450 Han and 22 478 Mongolian) were recruited, the survey response rate was 96.09% (46 928/48 836). In one-year-period analysis, the menarche age gradually decreased from 1951 to 2005. The mean menarche age of Han and Mongolian women changed from (16.22±0.52) years and (15.86±1.24) years in 1951 to (12.37±1.15) years and (12.33±0.98) years in 2005, respectively. The mean menarche age of Han and Mongolian women decreased 3.85 years and 3.54 years. The trend of the mean menarche age's change showed a significant negative correlation with the years (all P<0.000 1). In five-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.54±1.45) years and (15.53±1.48) years from 1951 to 1955 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.13 years (3.41 months ahead of schedule every 5 years on average) and 3.06 years (3.34 months ahead of schedule every 5 years on average) in Han and Mongolian women respectively. In ten-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.79±0.95) years and (15.53±1.33) years from 1951 to 1960 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.38 years (6.76 months ahead of schedule every 10 years on average) and 3.06 years (6.12 months ahead of schedule every 10 years on average) in Han and Mongolian women respectively. During the 15 years from 1951 to 1965, 1966 to 1970, 1971 to 1990, and 1991 to 2000, they were concentrated at the ages of 15-16, 14-15, 13-14, and 12-13, respectively. The proportion of women at 11 years, 12 years and 13 years menarche age were 26.79% (457/1 706), 73.27% (1 250/1 706), and 92.85% (1 584/1 706) during 2001—2005 in Han women, while the proportion were 23.25% (653/2 809), 62.01% (1 742/2 809), and 90.14% (2 532/2 809) in Mongolian women. Conclusion:The menarche age decreased in Han and Mongolian women from 1951 to 2005, and the ethnic groups tended to be the same. It is recommended to start adolescent education at the age of 8-9 years and pay attention to the changing pattern of early onset of menarche.

Objective:To evaluate the positive rate of the bronchodilation test (BDT) in asthmatic children with normal forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC) and FEV 1/FVC, so as to improve the recognition of the importance of the BDT test in asthmatic children with normal FEV 1, FVC and FEV 1/FVC. Methods:Children aged 5-14 who were diagnosed with asthma in the outpatient clinic of Shandong Provincial Hospital Affiliated to Shandong University from September 2018 to August 2019 and willing to receive pulmonary function and BDT examinations were enrolled.Data of pulmonary function of children with normal FEV 1, FVC and FEV 1/FVC were collected to analyze the rate of positive BDT results and the status of small airway function. Results:A total of 1 631 asthmatic children with normal FEV 1, FVC and FEV 1/FVC were enrolled in this study, including 1 414 children with normal pulmonary function and 217 children with small airway dysfunction.Fifteen minutes after the bronchodilator was inhaled, 127 children (87 males and 40 females) showed positive BDT results, accounting for 7.8%.Among these children, 62 cases (28.6%) with co-existing small airway dysfunction showed positive BDT results.The improvement rate of FEV 1 was 8.0% to 11.9% in 132 cases (8.1%). The FEV 1 before bronchodilator inhalation accounted for (98.5±10.3)% of the predicted value.Fifteen minutes after terbutaline sulfate inhalation, the improvement rate was 13.5% (12.5%, 16.2%). The improvement rates of forced expiratory flow at 50% of FVC exhaled (FEF 50, r=-0.339, P<0.01), forced expiratory flow at 75% of forced vital capacity exhaled (FEF 75, r=-0.400, P<0.01), maximum mid-expiratory flow(MMEF, r=-0.375, P<0.01) were negatively correlated with their baseline values.The improvement rate of FEV 1 was not associated with its baseline value ( r=-0.128, P=0.153), but negatively correlated with the baseline value of MMEF ( r=-0.231, P<0.01). Conclusions:BDT results are positive in some asthmatic children with normal FEV 1, FVC and FEV 1/FVC.It is recommended that BDT testing should be conducted as much as possible in the diagnosis and follow-up of children with typical or atypical asthma.In this way, the diagnosis can be confirmed and the current optimal results can be obtained.Meanwhile, small airway function testing is helpful for comprehensive assessment of asthma and its control level.

Fine particulate matter (PM2.5) not only directly damages lung tissue, but also can be absorbed into blood through alveolar capillaries, which is toxic to the cardiovascular system. PM2.5 can affect lipid metabolism, endothelial function, coagulation and thrombosis through oxidative stress, inflammatory reaction, autonomic nervous dysfunction and immune regulation abnormality, so that it promote arteriosclerosis, plaque instability, and increase the morbidity and mortality of cardiovascular disease. We reviewed the effects and mechanisms of PM2.5 on arteriosclerosis, in order to provide the evidence for the studies into prevention of cardiovascular diseases caused by air pollution.

Objective: To screen and verify the differential expression profiles of long non-coding RNAs(LncRNAs) in peripheral blood of patients with type 2 diabetes mellitus(T2DM), to identify the potential molecular specific markers of early T2DM. Methods: The blood samples of 4 type 2 diabetic patients and 4 normal control subjects were collected for microarray analysis. Then six candidate markers of LncRNAs screened from the differential expression profile were tested by qRT-PCR among the subjects (80 cases in the T2DM group and 50 cases in the control group). The possibility of these LncRNAs as molecular diagnostic markers was analyzed, and finally two of them were carried out by receiver operating characteristic (ROC) analysis. Results: Compared with control subjects, there were differentially expressed 133 LncRNAs in type 2 diabetic patients, among which 5 were up-regulated with the maximum up-regulated fold 3.29 and 128 were down-regulated with the maximum down-regulated fold 8.99. Six down-regulated LncRNAs were selected for validation and revealed a similar result to that of microarray.The expressions of two LncRNAs(NONHSAT160746 and NONHSAT140069) in peripheral blood of diabetic patients were significantly lower than those of control subjects (P<0.01). The areas under the ROC curve of the two LncRNAs were 0.734 and 0.703, respectively(P<0.01). Conclusion LncRNAs NONHSAT160746 and LncRNAs NONHSAT140069 are the potential molecular specific markers for the diagnosis of diabetes mellitus.

Background and purpose:Breast invasive ductal carcinoma (IDC) is the most common breast carci-noma, and the ultrasonographic features of its molecular subtypes has great clinical value. The purpose of this study was to discuss the correlation between ultrasonographic features of IDC and its molecular subtypes.Methods:Ultrasonographic features of 112 patients with preoperative integrated ultrasonographic information and pathologically confirmed IDC from Sep. 2012 to Feb. 2015 were retrospectively analyzed. Based on the immunohistochemistry results of ER (estrogen receptor), PR (progesterone receptor), HER-2 (human epidermal growth factor receptor-2) and Ki-67, these cases were categorized into 4 molecular subtypes: Luminal A group, Luminal B group, ERBB2 positive group and Basal-like group. Results:There were 14 cases (12.5%) in Luminal A group, 62 cases (55.4%) in Luminal B group, 21 cases (18.7%) in ERBB2 positive group and 15 cases (13.4%) in Basal-like group. The 4 molecular subtypes differed in tumor length, lymph node involvement, tumor boundary, tumor shape and internal blood flow on ultrasonography (P<0.05). There were no sig-nificant differences in tumor internal echo, posterior echo, micro-calcification and elastrography between subtypes (P>0.05).Luminal A group and Luminal B group had less lymph node involvement, more obscure boundary and irregular shape. More internal blood flow, bigger tumor size and lymph node involvement were observed in ERBB2 positive group of this study. Patients in Basal-like group were more likely to have clear tumor boundary, regular tumor shape, bigger tumor size and lymph node involvement on ultrasonogram.Conclusion:Correlation exists between ultrasonographic features and molec-ular subtypes of IDC. This has tremendous clinical significance in the early diagnosis of IDC, preoperative, intraoperative and prognosis evaluation of IDC patients.