Identification of a functional mRNA-miRNA network in mTEC development

The adaptive immune system with its diversity of immune cells and their receptors allows an effective fight against a plethora of pathogens. The development of T cells is taking place in the thymus, where it undergoes two selections that is immensely important to ensure self-tolerance. For those two strictly regulated selection processes there are two major cell components being responsible for that called cortical thymic epithelial cells (cTEC) and medullary thymic epithelial cells (mTEC). MTECs are playing an important role for the prevention of autoimmune diseases as they express self-antigens to the maturing T cells. The current knowledge describes basically the function of cTECs and mTECs, the development of a stem cell to mTEC, the involvement of molecular mechanisms which influences the development of thymus and mTECs, still not in every single details. To date molecular details are still missing how an immature mTEC develops to a mature mTEC, especially molecular mechanisms, which influence the maturation and what controls each single step to its final maturation. Previous researches have found in the immature mTECs four new subpopulations present in fetal and embryonic mTECs, which have not been shown in adult mice. Until now only a handful of microRNAs (miRNAs) have been found to play a role in mTECs, but no miRNAs have been founds to play an active role in the maturation process of mTECs. The scope of this doctorate thesis was to characterise the four subpopulations in adult mice with the help of mRNA and miRNA microarray analyses. With the help of the mRNA gene arrays we could decipher a lineage sequence within the four subpopulations stating that Sca1 as the most progenitor population Sca-1 < DP < CD24 < DN. According to the analyses DN was the closest cell population to mature mTECs, probably one step before coming a mature mTEC. Thereupon we used bioinformatics to filter the most prominent miRNAs, which might play an important role in the development of the four subpopulations. Those miRNAs were verified by using a SCID mouse model, which emulates the dynamic development of the four subpopulations. Subsequently we inhibited or overexpressed those miRNA candidates in freshly isolated mTECs to see their influence of the development of the four subpopulations. At the end we found 11 promising miRNAs that play a role in the maturation of the four subgroups. This finding resulted in a deeper search for possible mRNA interaction partners for those miRNA candidates. After investigating 35 mRNAs we found 4 miRNA-mRNA interactions, which have not been described in the mTEC development before. Following miRNA-mRNA networks have been found: miR-34a interacts with Foxp1, Mir-125b-5p with Bak1 and Mapk14, miR-125a-3p with Fam83e. This thesis completes the understanding of the four subpopulations in adult mice as well discovered 4 new miRNA-mRNA interactions, which are important for the maturation of the four subpopulations. With this newly gained knowledge we can apply it to the human thymus and their mTEC development with the hope to boost the thymus function after chemotherapy and organ transplantations

Numerical simulation and experimental investigation of the laser cladding processes of Ti6Al4V with coaxial shroud protection

Laser cladding with coaxial shroud protection offers the possibility to process reactive metals in an open environment. The numerical analysis was performed on the thermal field and dynamics of molten pool with the aim of clarifying the mechanism of the complex effects of the applied extra shielding gas on the resultant microstructure and surface quality of cladding layers of Ti6Al4V. A three-dimensional (3D) computational fluid dynamics (CFD) model was first developed to investigate the extra shielding gas effect on the molten pool. The simulation shows that the extra shielding gas influences both the surface and internal flow field characteristics of the molten pool. The predicted solidification parameters imply fully columnar microstructure in the entire cladding layer. Comparative analysis was then carried out between the numerical simulation and experiments. The electron backscattering diffraction (EBSD) examination reveals that the high cooling rate due to the extra shielding gas inhibits the formation of grain boundary α phase and simultaneously refines the microstructure. The extra shielding gas reduces the surface roughness of cladding layers, and its bunching effect improves the powder utilization. The multi-track cladding experiments reveal that the extra shielding gas can effectively suppress crack formation with a large overlap ratio. This study provides a better understanding of the effect of extra shielding gas flow on molten pool, which helps control and improve the quality of cladding layers

Negative Perceptions of Urban Tourism Community in Beijing: Based on Online Comments

The development of urban tourism community (UTC) will bring new vigor and vitality into the urban sustainable development. There are abundant tourists’ comments about personal experience in UTC in online travel communities, which provide good access to the knowledge of negative perceptions of urban tourism community. Based on online comments, this paper used content analysis method to research tourists’ negative perceptions about five typical tourism communities in Beijing, whereby the common problems and special problems of UTC were identified. According to the research results, the authors made suggestions to the sustainable development of UTC in Beijing

Addressing Parental Smoking in Pediatric Settings of Chinese Hospitals: A Qualitative Study of Parents

This study explored factors associated with SHS exposure from parental smoking in Chinese families and assessed nature of antismoking discussions parents had with their children's pediatricians and how pediatricians might best engage with parents in an effort to reduce children's exposure to SHS. Six focus group discussions (FGDs) were conducted among 33 Chinese parents attending six major hospitals in Guangxi province, China. Most participants (32/33) had family members who smoke, and only 21% had strict restriction on smoking at home. Some parents did not know about health consequences of smoking and effects of SHS exposure on children. Situations that made it especially hard to avoid the child's SHS exposure were having an elderly smoker at home and having a visitor who smoked. Only few parents were asked by pediatricians about child's exposure to SHS at home, but only when child's illness was related to smoking. Parents believed that suggestions coming from pediatricians about smoke-free home and parental quitting would be acceptable to parents and other household members. The findings provide insight into SHS exposure reduction effort among Chinese parents and underscore the demand for pediatrician's engagement in addressing parental tobacco use

Secondhand smoke exposure assessment and counseling in the Chinese pediatric setting: a qualitative study

Background: Assisting smoking parents to quit smoking and eliminating the secondhand smoke (SHS) exposure of their children is a global health priority. Engaging healthcare workers in developing countries to address this priority has been a challenge. This study intends to explore issues around current practice related to SHS exposure assessment and counseling and identify barriers to SHS exposure reduction counseling in the Chinese pediatric setting. Methods: We conducted qualitative interviews (11 focus groups discussions (FGDs) with pediatricians, 6 FGDs with pediatric nurses and 11 in-depth interviews (IDIs) with hospital administrators) among 101 health-care professionals (HCP) from 5 hospitals in four major cities of Guangxi Province, China. All FGDs/ IDIs were audio recorded and analysed thematically. Results: The findings suggest that few Chinese pediatricians routinely address the SHS exposure of children in their usual practice. All HCPs felt the need for clinical interventions to promote SHS exposure reduction for children. Primary barriers to SHS exposure reduction counseling in the Chinese pediatric setting included: lack of skills and training in tobacco use reduction and cessation counseling; time constraints and heavy workloads, uncertainty about the usefulness of smoking cessation interventions and lack of hospital-wide systems requiring pediatricians to record tobacco use or SHS exposure information. Ideas for overcoming these barriers were building capacity of pediatricians, collaboration with international organization to initiate training, engaging top level leaders in the effort and ensuring financial resources to support the program. Conclusions: This study among hospital administrators and service providers in China demonstrated a high level of interest in delivering SHS exposure reduction interventions in the pediatric setting. The findings can inform the creation and delivery of clinical interventions in China to promote SHS exposure reduction to children in the pediatric setting. Electronic supplementary material The online version of this article (doi:10.1186/1471-2431-14-266) contains supplementary material, which is available to authorized users

The Efficacy and Safety of Diyushengbai Tablet on Preventing and Treating Leukopenia Caused by Radiotherapy and Chemotherapy Against Tumor: A Systematic Review and Meta-Analysis

Background: Leukopenia is one of the side effects of radiotherapy and chemotherapy. Diyushengbai tablet (DYT) is used to prevent and treat leukopenia caused by various reasons. A meta-analysis was performed to systematically analyze the therapeutic effects of DYT on preventing and treating leukopenia caused by radiotherapy and chemotherapy.Objectives: This study aimed to systematically evaluate the efficacy and safety of DYT in preventing and treating leukopenia caused by radiotherapy and chemotherapy.Methods: We performed a comprehensive literature search of electronic databases such as PubMed, The Cochrane Library, China Knowledge Network (CNKI), China Biomedical Literature Database (CBM), Wanfang Data Knowledge Service Platform, and VIP, through November of 2021. The scanning reports deadline is until November 2021. The bias risk evaluation criteria developed by the Cochrane collaborative organization were used to evaluate the literature quality of the included studies. The RevMan5.4 software was used to analyze the data, and the Stata16.0 was used to perform the Egger test.Results: After selecting all the databases, a total of 41 reports which involved 3,793 cases were analyzed. Meta-analysis showed that DYT could significantly reduce the white blood cell (WBC) suppression caused by radiotherapy and chemotherapy and improve the patients’ WBC counts and neutrophils, compared with the efficacy of other oral WBC-elevating drugs such as Leucogen tablets and Batilol tablets and additional utilization of granulocyte colony-stimulating factor (G-CSF). The results of meta-analysis showed that for preventive medication purpose, the overall incidence of leukocyte suppression was [RR = 0.74, 95%CI (0.59, 0.92), p = 0.006], and the white blood cell count was [MD = 1.12, 95%CI (0.95, 1.29), p &lt; 0.00001]; while for therapeutic purpose, the incidence of overall leukocyte suppression was [RR = 0.61, 95%CI (0.38, 0.95), p = 0.03], and the white blood cell count was [MD = 1.20, 95%CI (0.77, 1.62), p &lt; 0.00001]. More importantly, the additional use of DYT can reduce the application amount of G-CSF. The results showed that the application of G-CSF can be reduced by an average of 1.57 from the beginning of treatment to return normal white blood cells around 2.23 in two cycles of chemotherapy.Conclusion: DYT is more effective in preventing and treating leukopenia caused by radiotherapy and chemotherapy than other oral WBC-elevating drugs, which have a high clinical value

Are Chinese pediatricians missing the opportunity to help parents quit smoking?

Background: Secondhand smoke (SHS) exposure of children due to parental tobacco use is a particularly prevalent health issue and is associated with adverse health outcomes. Following the US Clinical Practice guidelines, pediatricians in the United States deliver 5A’s (ask, advise, assess, assist, and arrange) counseling to smoking parents which has proven to be effective. We examined Chinese pediatricians’ adherence to the clinical practice guidelines for smoking cessation (i.e. 5A’s counseling practices) with smoking parents, and identified factors associated with these practices. Methods: A cross-sectional paper-and-pencil survey of pediatricians was conducted in twelve conveniently selected southern Chinese hospitals. Factors associated with any of the 5A’s smoking cessation counseling practices were identified by logistic regression. Results: Of respondents (504/550), only 26 % routinely provided 5A’s smoking cessation counseling to smoking parents. More than 80 % of pediatricians didn’t receive formal training in smoking cessation and had not read China smoking cessation guidelines; 24 % reported being “very confident” in discussing smoking or SHS reduction with parents. Pediatricians who had never smoked (OR: 2.29, CI:1.02-5.12), received training in smoking cessation (OR: 2.50, CI:1.40-4.48), had read China smoking cessation guidelines (OR: 2.17, CI:1.10-4.26), and felt very (OR: 7.12, CI:2.45-20.70) or somewhat (OR: 3.05, CI:1.11-8.37) confident in delivering cessation counseling were more likely to practice 5A’s. Pediatricians who reported “it is hard to find a time to talk with parents” (OR: 0.32, CI: 0.11-0.92) or “lack of a standard of care requiring pediatricians to provide smoking cessation or SHS exposure reduction intervention” (OR: 0.45, CI: 0.21-0.98) as a barrier were less likely to follow the 5A’s guidelines. Conclusions: Smoking cessation counseling to address parental smoking is infrequent among Chinese pediatricians. There is a need to develop and test intervention strategies to improve the delivery of 5A’s smoking cessation counseling to parental smokers

Chinese pediatrician beliefs about counseling and medications for parents who smoke: a survey in southern China

Background: Pediatricians play an important role in promoting smoking cessation among the parents of young children as more behavioral counseling and cessation treatment are made available in the Chinese healthcare system. However, beliefs about the effectiveness of these interventions can influence pediatricians’ recommendations to their patients. This study examined pediatricians’ beliefs regarding effectiveness of counseling and medications for smoking cessation. Methods: A cross-sectional survey of pediatricians was conducted in thirteen conveniently selected southern Chinese hospitals, during September to December 2013. A self-administered questionnaire was used for data collection. We used chi square tests and multinomial logistic regression analysis to identify factors associated with beliefs regarding effectiveness of counseling and medications for smoking cessation. Results: Beliefs of the respondents (504/550; 92% response rate) were divided regarding the effectiveness of counseling and medications for smoking cessation. Sixty percent believed that physician counseling is effective for smoking cessation; 53% believed pharmacological products (or medications) are effective. Factors that were associated with positive beliefs towards the effectiveness of counseling included: believing about the professional responsibility to discuss smoking cessation, being confident in discussing smoking cessation or SHS exposure reduction with patients’ parents, believing that health professionals should routinely ask about their patients smoking habits, believing that health professionals should routinely advise their smoking patients to quit smoking, possessing adequate knowledge in quitting smoking, and being able to assess smokers different stages of readiness to quit. Most of the above factors were also associated with the belief that medication is effective for smoking cessation. Conclusions: A substantial proportion of Chinese pediatricians believed that cessation counseling and medications are not effective, which is not supported by current evidence in the field. Several factors including individual, practice level and health system level characteristics were associated with their belief. Training efforts are needed to influence pediatricians’ beliefs regarding the effectiveness of cessation counseling and medications