Prevalence of job burnout and associated influencing factors among healthcare workers in China / 环境与职业医学

Background Healthcare workers suffer from great internal and external pressure and are prone to burnout. Existing studies have shown that depressive symptoms are important influencing factors of burnout, both of which are closely related to job stress. Objective To analyze overall prevalence of burnout among healthcare workers using a new survey tool developed by our team, and to reveal potential influencing factors related to burnout. Methods A cross-sectional multi-center study was conducted in August–October 2019 and June–September 2020, using multi-stage stratified cluster sampling. A total of 8738 healthcare workers from 22 hospitals in 5 provinces (Shandong, Hubei, Hunan, Guangdong, and Chongqing) of China were selected in this study. A set of survey questionnaires, including the general information questionnaire and the Chinese versions of General Burnout Scale, Core Occupational Stress Scale, Patient Health Questionnaire-9, and Self-administered Sleep Questionnaire were distributed. Independent samples t-test or one-way ANOVA were employed for inter-group comparison of burnout. Spearman correlation was used to evaluate correlations among burnout, depressive symptoms, and occupational stress. Stepwise linear regression was conducted to identify factors independently associated with burnout. Process plug-in was used to test potential mediating effect of depressive symptoms on occupational stress and burnout. Results Of the 8738 questionnaires distributed, 8456 valid questionnaires were collected, and the recovery rate was 96.77%. Among the 8456 healthcare workers, the prevalence of burnout was 58.0%, that of occupational stress was 31.8%, and that of depressive symptoms was 31.0%. Among those with depressive symptoms and occupational stress, the proportions of burnout were 86.7% and 83.7%, respectively. According to the stepwise linear regression analysis, depressive symptoms, occupational stress, work experience, drinking, and marital status were all independent influencing factors of burnout. Especially, depressive symptoms, social support, and organization and reward had significant influences on burnout (b'=0.455, −0.183, 0.220, P<0.001). Depressive symptoms showed mediating effects on occupational stress (and its subscales) and burnout, and the contribution rates of the mediating effects were 41.00%, 47.02%, 43.44%, 56.62%, and 59.45%, respectively. Conclusion Burnout is a prominent problem among healthcare workers in the 5 provinces, with the prevalence of 58.0%. And nearly 1/3 suffering from depressive symptoms and occupational stress, which has a great impact on burnout.

Job burnout and influencing factors among Chinese manufacturing employees / 环境与职业医学

Background Manufacturing industry is the main body of China's national economy, and manufacturing employees provide solid guarantee and support for the vigorous development of China's manufacturing industry. The research on job burnout of manufacturing employees is helpful to prevent or alleviate the health damage and economic loss caused by job burnout. Objective To investigate the status and influencing factors of job burnout among manufacturing employees in China, and evaluate the potential mediating effect of job burnout between job stress and depressive symptoms. Methods A cross-sectional study was performed from August to October 2019 and from June to September 2020 in seven provinces of China. Study participants were recruited from 21 manufacturing companies covering 11 manufacturing subdivisions using multistage stratified cluster sampling. General Burnout Scale, Core Occupational Stress Scale, and Patient Health Questionnaire-9 were used to evaluate job burnout, job stress, and depressive symptoms. Mann-Whitney U test and Kruskal-Wallis H test were used to compare data between two independent samples and multiple independent samples of measurement data; Pearson χ2 test was used to compare the rate of enumeration data; Spearman rank correlation analysis was used to evaluate correlation between selected variables; binary logistic regression was used for multivariate analysis; stepwise regression and bias-corrected Bootstrap method were used to test potential mediating effect. Results A total of 10973 valid questionnaires were collected. The M (P25, P75) scores of exhaustions, cynicism, professional efficacy, job burnout, job stress, and depressive symptoms were 1.6 (0.4, 3.0), 1.0 (0.2, 2.2), 4.8 (3.2, 5.7), 1.6 (0.8, 2.5), 45.0 (40.0, 50.0), and 7.0 (4.0, 11.0), respectively. The positive rates of job burnout, job stress, and depressive symptoms were 53.4% (5865/10973), 28.4% (3116/10973), and 29.4% (3231/10973), respectively. The influencing factors of job burnout were gender (versus male; OR for female=0.852), age (versus≤25 years old; ORs for 26-30, 31-40, 41-50, 51-60 years old=0.824, 0.819, 0.738, 0.677), education level (versus junior high school or below; ORs for senior high school/technical secondary school, junior college/vocational college, graduate school or above=1.119, 1.345, 1.331), income per month (versus＜3000 yuan; ORs for 3000-4999, 5000-6999, 7000-8999, 9000-10999, ≥11000 yuan=0.513, 0.470, 0.430, 0.375, 0.411), position (versus assembly line; OR for non-assembly line=0.814), average weekly working hours (versus ≤40 h; ORs for 61-70, ＞70 h=1.199, 1.519), and drinking (versus non-drinking; OR for drinking=1.261). Job burnout was positively correlated with job stress and depressive symptoms (r=0.556, 0.508, P<0.001). Job burnout played a partial mediating role between job stress and depressive symptoms, and its contribution value accounted for 63.2% of the total effect. Conclusion Manufacturing industry employees' job burnout problem is prominent in China, and there are many factors affecting job burnout. Job burnout may play a partial mediating role between job stress and depressive symptoms in the target group.

Reliability and validity of General Burnout Scale in multiple populations / 环境与职业医学

Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ2/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ2/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P<0.05) in overall subjects. For traffic police and firefighters, professional efficacy was not correlated with depressive symptoms or sleep disorders (P>0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups. Conclusion The GBS shows high reliability and validity, as well as good application effects in different occupational groups.

Analysis of the pathogenic spectrum and epidemiological characteristics of 520 children with influenza-like illnesses in Tianjin / 中华微生物学和免疫学杂志

Objective:To understand the epidemiological characteristics and pathogenic spectrum of influenza-like illnesses in Tianjin Children′s Hospital from October 2020 to March 2021, and to provide reference for the prevention, control and clinical diagnosis and treatment of influenza-like illnesses.Methods:A total of 520 throat swabs samples were collected from patients with influenza-like illnesses in sentinel hospitals. Thirty respiratory tract pathogens were detected by real-time fluorescence quantitative PCR. The results were statistically analyzed by descriptive epidemiological methods.Results:Among the 520 samples, 239 were positive for 16 respiratory pathogens with a positive rate of 45.96%. The top three pathogens were respiratory syncytial virus (9.62%, 50/520), rhinovirus (9.62%, 50/520) and cytomegalovirus (5.96%, 31/520). The positive rate of respiratory pathogens was 49.67% in males and 40.91% in females and the difference between males and females was statistically significant (χ 2=3.919, P<0.05). There were significant differences in the positive rates among three age groups (χ 2=6.182, P<0.05) with the highest positive rate in the <2 years old group (52.91%, 91/172) and the lowest rate in the >4 years old group (38.10%, 40/105). There were significant differences in the positive rates detected in different months (χ 2=15.358, P<0.05) and the highest detection rate was in December (58.00%, 58/100), followed by those in November (52.50%, 42/80) and January (47.50%, 38/80). The multiple infection rate was 21.76% (52/239) and most of the multiple infections were caused by rhinovirus and other pathogens (48.08%, 25/52). Conclusions:Respiratory syncytial virus, rhinovirus and cytomegalovirus were the predonimant pathogens responsible for influenza-like illnesses in Tianjin Children′s Hospital from October 2020 to March 2021. Multiple infections were common and children under 2 years old were more susceptible. The detection rate of respiratory pathogens varied in different months. It was necessary to strengthen the surveillance and research on those respiratory pathogens in order to provide scientific data for the prevention and control of respiratory diseases in children.

Status of sleep and exercise during remote learning period for primary school students in one city during the outbreak of COVID-19 / 中国学校卫生

Objective@#To explore the relationship between sleep and exercise among grade 1-6 students in a certain city during the period of home based online courses in the epidemic, and to provide reference basis for the government and relevant departments to make relevant policies on student health promotion.@*Methods@#From April 22 to May 14 in 2020, 24 452 primary school students were selected by stratified cluster random sampling method to network questionnaire survey, which included general situation, sleep time,and exercise.@*Results@#Totally 21.6% of primary school students participated in low intensity exercise, 9.4% in moderate intensity exercise and 5.8% in high intensity exercise every day. Less than 10% of the students participated in all types of intense sports for more than 30 minutes each time. The report rate of sleep deprivation among students in grades 1 to 6 was 22.5%, 25.5%, 28.9%, 31.3%, 35.0%, 39.9%, respectively(χ 2=350.75, P<0.05). Multivariate Logistic regression analysis showed that after adjusting for gender, grade, oneness and other factors, high intensity exercise was negatively correlated with sleep deprivation(OR=0.91, 95%CI=0.86-0.97).@*Conclusion@#Insufficient sleep is common among primary students, and appropriate amount of high intensity exercise is a favorable factor to ensure adequate sleep time in primary school students.

Effect of long working hours on work related musculoskeletal disorders and job burnout in internet enterprise employees / 中国职业医学

OBJECTIVE: To investigate the current status of long working hours among employees of internet enterprises, and explore its effects on work related musculoskeletal disorders(WMSDs)and job burnout. METHODS: A total of 3 589 employees from 35 internet enterprises in 3 provinces were selected as the research subjects using the method of cluster sampling.The Questionnaire of Musculoskeletal Disorders and Maslach Burnout Inventory-General Survey was used to assess employees′ WMSDs and job burnout, and to explore the influence of long working hours(>40 hours per week) on WMSDs and job burnout. RESULTS: The average weekly working hours of these workers were(48±11) hours, and the workers working for long-hour accounted for 68.0%(2 442/3 589). The prevalence of WMSDs was 80.4%(2 886/3 589), and the detection rate of job burnout was 10.5%(376/3 589). The results of binary logistic regression analysis showed that long working hour was the influencing factor of WMSDs and job burnout after removing confounding factors including gender, age, education level, marital status, income, exercise frequency, diet habit, smoking status, type of work and length of service(P<0.01). The longer the weekly working hour, the higher the risk of WMSDs and job burnout. CONCLUSION: Long working hour increases the risk of WMSDs and job burnout with a dose-response relationship in internet enterprise employees.

The influencing effects of effort reward imbalance on sleep disorders among metro staff in Guangzhou / 中华劳动卫生职业病杂志

Objective@#To detect the prevalence of sleep disorders among metro staff and to analyze influencing effects of effort reward imbalance (ERI) on it.@*Methods@#In January 2015, subway driver, dispatcher and station operator from Guangzhou subway were selected as the research object in the whole group sampling method. A total of 1200 questionnaires were distributed and 1124 were valid questionnaires, and the effective questionnaire recovery rate was 93.7%. Based on the effort reward imbalance questionnaire and the self-administered sleep questionnaire, the data of the general demographic characteristics, life satisfaction, occupational stress and sleep status of the respondents were collected. Epi.data3.1 and spss19.0 were used for analyzing.@*Results@#A total of 1124 subway employees were surveyed, with an average age of (28±5) years; the working age was (4.5±3.6) years. ERI occupied 24.7% (278/1124) of the study population and sleep disorders as 42.2% (474/1124) . Single factor analysis showed that marital status, educational level, work position, life satisfaction and ERI could significantly influence sleep disorders of metro staff (P<0.05) . Logistic regression showed that higher effort (adjusted OR=2.56, 95%CI: 1.79-3.68) , lower reward (adjusted OR=1.90, 95%CI: 1.34-2.68) and ERI (adjusted OR=2.33, 95%CI: 1.69-3.22) could increase the risk of sleep disorders after the confounding factors were controlled. ERI (adjusted OR=2.89, 95% CI: 1.80-4.64) , and over commitment (adjusted OR=4.64, 95%CI: 2.81-7.68) could influence the risk of sleep disorders independently when over commitment was evaluated as a moderating variable.@*Conclusion@#Occupational stress as ERI could influence the risk of sleep disorders among metro staff. The situation should not be neglected for occupational health of metro staff.

Advances in Research on Nrf2 Signaling Pathway in Inflammatory Bowel Disease / 胃肠病学

Nuclear factor-erythroid 2 related factor-2 (Nrf2) is the main protective molecule of cells against external pressure with an anti-oxidative stress and anti-inflammatory effect. Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease with a high risk of developing intestinal fibrosis and colorectal cancer. Many studies have confirmed that Nrf2 and its downstream pathway play important roles in IBD intestinal fibrosis and carcinogenesis. Therapeutic drugs targeting Nrf2 signaling pathway are being widely studied. This article reviewed the advances in research on Nrf2 signaling pathway in IBD.

Mediating role of psychological capital in occupational stress and depressive symptoms among employees working in an assembly-line of electronic manufacturing service industry / 中国职业医学

OBJECTIVE: To analyze the association of depressive symptoms,occupational stress and psychological capital( Psy Cay) in employees working in an assembly-line of electronic manufacturing service industry( EMSI),and discuss the mediating effect of Psy Cap in occupational stress and depressive symptoms. METHODS: A total of 2269 employees who work in an assembly-line from 9 EMSI enterprises in Beijing City,Jiangsu and Guangdong Provinces were selected as study subjects by a cross-sectional survey method. The Patient Health Questionnaire,Effort-Reward Imbalance Scale and Psy Cap Questionnaire were used to investigate their depressive symptoms,occupational stress and Psy Cap. The hierarchical regression analysis was used to explore the effects of occupational stress and Psy Cap on depressive symptoms. The mediating role of Psy Cap was examined using asymptotic and resampling strategies. RESULTS: The detection rate of depressive symptoms was 26. 0%( 589/2 269),and the detection rate of effort-reward imbalance model occupational stress was 26. 6%( 603/2 269). The total score of depression symptoms was positively correlated with the scores of the occupational stress effort and over-commitment dimensions [Spearman correlation coefficient( rS) were 0. 22 and 0. 34,respectively,P < 0. 01),and negatively correlated with the scores of the occupational stress reward dimension and the total score of Psy Cay( rSwere-0. 37 and-0. 39,respectively,P < 0. 05). Psy Cap plays a partial mediating role between the dimensions of effort and reward of occupational stress and depressive symptoms,and the mediating effect percentage was14. 8% and 23. 7% respectively. CONCLUSION: The Psy Cap of employees of EMSI assembly-line plays a partial mediating effect in occupational stress effort,reward and depressive symptoms. Increased levels of Psy Cap will help alleviate depressive symptoms.

Factors associated with fatigue in the employees of internet companies / 中华劳动卫生职业病杂志

Objective@#To explore factors associated with fatigue in employees working in Internet companies.@*Methods@#A cross-sectional study was conducted among 3603 employees from 35 internet companies. A self-conducted questionnaire was used to assess employees’ fatigue and related factors.@*Results@#The scores of body fatigue, mental fatigue and total fatigue were (4.53±2.56) , (2.37±1.64) , and (6.90±3.55) respectively. The body fatigue is positively correlated with job burnout and musculoskeletal disorders (r=0.426, 0.485) ; the mental fatigue is positively correlated with job burnout (r=0.429) . JDC and ERI occupational stress, burnout and high level of musculoskeletal disorders increased the risk of body fatigue of which odds ratios are 1.58, 1.72, 4.08 and 5.91; odds ratios for the risk of mental fatigue are 1.73, 1.37, 2.61 and 2.08. Sleep time over 7 hours reduces the risk of fatigue (P<0.05) with odds ratio of 0.61 and 0.62.@*Conclusion@#Employees of Internet companies is facing fatigue issues. To protect employee’s physical and mental health is highly important for employers to alleviate fatigue and improve work performance.

Association of occupational stress with job burnout and depression tendency in workers in Internet companies / 中华劳动卫生职业病杂志

Objective@#To investigate the association of occupational stress with job burnout and depression tendency in workers in Internet companies. @*Methods@#From July to November, 2016, the cross-sectional method was used to perform a questionnaire survey of 3603 workers in 35 Internet companies in Beijing, Shandong Province, and Zhejiang Province in China, and the association of occupational stress with job burnout and depression tendency was analyzed. @*Results@#Among these workers, 63.70% had occupational stress with job demand-control (JDC) and 34.60% had occupational stress with effort-reward imbalance (ERI) ; among the workers engaged in sales, 75.63% had occupational stress with JDC and 62.70% had occupational stress with ERI. Of all workers, 10.69% had job burnout, and among the workers engaged in sales, 22.12% had job burnout. Of all workers, 18.79% had the tendency of moderate-to-severe or severe depression, and among the workers engaged in sales, 46.13% had such tendency. Occupational stress with JDC increased the risk of job burnout and depression (odds ratio[OR]=3.52 and 1.85, P<0.05) , and occupational stress with ERI also increased the risk of job burnout and depression (OR=8.24 and 5.59, P<0.05) . In addition, irregular diet and insomnia were risk factors for job burnout; age ≥41 years, low income, sales position, working time spent on the screen ≥10 hours/day, insomnia, and poor self-evaluated health status were risk factors for depression tendency. @*Conclusion@#Occupational stress with JDC and ERI increases the risk of job burnout and depression tendency, and among the workers in Internet companies, the workers engaged in sales have the most severe occupational stress, job burnout, and depression tendency.

Mediating role of over-commitment in the relationship between effort, reward and burnout / 中华劳动卫生职业病杂志

Objective@#To explore the mediating role of over-commitment in the relationship between occupational stressors and job burnout, and to offer more specificevidence-based information in exploring the work related health effects of over-commitment.@*Methods@#A total of 1994 samples from electronic manufacturing service industry were collected in Guangdong province based on self-rated questionnaire after written consent from June to July, 2015. The Effort-Reward Imbalance questionnaire and Maslach Burnout Invertory-General Survey were used for the measurement of occupational stress and job burnout. And hierarchical regression and Bootstrap test were conducted for data analysis.@*Results@#High effort (0.28, 0.24-0.33) and low reward (-0.37, -0.42--0.33) were significantly associated with high over-commitment when gender, age and position had been controlled. Standardizedregression coefficient of effort to emotional exhaustion, depersonalization and personal accomplishment were 0.63 (95%CI: 0.54-0.71) 、0.18 (95%CI: 0.10-0.26) 、0.32 (95%CI: 0.21-0.43) , P<0.05; and standardized regression coefficient of reward to emotional exhaustion, depersonalization and personal accomplishment were-0.60 (95%CI: -0.68--0.52) 、-0.93 (95%CI: -1.01--0.86) 、-0.46 (95%CI: -0.35--0.58) , P<0.05. Bootstrap test indicated the mediation of over-commitment were statistically significant, and mediating effect ranges from 0.093 to 0.218 (P<0.05) .@*Conclusion@#Over-commitment can mediate the relationship between occupational stressors (job effort and reward) and burnout, and the effect varies from different workingconditions.

Construction and function identification of luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR / 药学学报

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.

Impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese renal transplant recipients / 中国药理学通报

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.

Effect of liraglutide combined with insulin on HbA1c, T lymphocyte subsets and islet function in patients with type 1 diabetes / 中国生化药物杂志

Objective To investigate the effect of liraglutide combined with insulin on the HbA1c, T lymphocyte subsets and islet function in patients with type 1 diabetes.Methods 46 cases from endocrinology department of Tangshan Traditional Chinese Medicine Hospital with type 1 diabetes were selected and randomly divided into two groups each group had 23 patients.Control group were given recombinant human insulin to control blood sugar according to the blood glucose level, and experimental group were given liraglutide on the basis of control group.HbA1c, T lymphocyte subsets, C-Peptide ( CP) and islet function were compared after treatment.ResuIts Compared with control group after treatment, HBAlc level in experimental group was lower (P<0.05); CD4 +T was higher, CD8 +T was lower, and CD4 +/CD8 +T was higher (P<0.05); the fasting plasma glucose (FPG) level was lower (P<0.05);2-hour postprandial blood glucose (2 hPG) was lower (P<0.05); CP and 2-hour postprandial C-Peptide (2 hCP) were higher (P<0.05).There was no significant difference in liver and kidney function between two groups.ConcIusion Liraglutide combined with insulin could significantly reduce serum glycated hemoglobin level, increase CD4 +T level and reduce CD8 +T level, improve islet function in patients with type 1 diabetic.

Associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients / 药学学报

The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4 (rs237024, rs237025) genotypes were detected by Sequenom® MassARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D' = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P < 0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.

TNFR-1 on tumor cells contributes to the sensitivity of fibrosarcoma to chemotherapy

Impaired tumor necrosis factor receptor-1 (TNFR-1) signaling has been found in some malignant tumors with poor prognosis. However, the exact role of TNFR-1 signaling in fibrosarcoma remains unclear. Here, we explored the question by comparing the growth of TNFR-1 deficient (Tnfr1 (-)) and TNFR-1 competent (Tnfr1 (+)) fibrosarcoma FB61 cells (FB61-m and FB61-R1) in mice. TNFR-1 expression on fibrosarcoma cells delayed their growth in vivo but not in vitro. Moreover, reduced FB61-R1 tumor growth was also obtained in TNFR-1 knockout mice. The mechanism relies mainly on the TNFR-1-mediated downregulation of vascular endothelial growth factor (VEGF) production by tumor cells. Importantly, treatment of FB61-m tumors with melphalan resulted in a short delay of tumor growth, followed by a quick remission. However, when FB61-R1 tumors were treated with melphalan, tumor growth was similarly delayed at first and then completely rejected. Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fibrosarcoma, and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.

Selective expansion and enhanced anti-tumor effect of antigen-specific CD4(+) T cells by retrovirus-mediated IL-15 expression

Mounting evidence has demonstrated that CD4(+) T cells play an important role in anti-tumor immune responses. Thus, adoptive transfer of these cells may have great potential for anti-cancer therapy. However, due to the difficulty to generate sufficient tumor-specific CD4(+) T cells, the use of CD4(+) T cells in tumor therapy is limited. It has been found that IL-15 transfection enhances the proliferation and anti-tumor activity of tumor-specific CD8(+) T cells, but the effect of IL-15 transfection on CD4(+) T cells remains unknown. Here, the effects of retrovirus-mediated IL-15 expression in Ova-specific CD4(+) T cells from Do11.10 mice were evaluated and it was discovered that IL-15 transfected CD4(+) T cells expressed both soluble and membrane-bound IL-15. Retrovirus-mediated IL-15 expression led to a selective expansion of antigen-specific CD4(+) T cells by inhibiting their apoptosis. In vivo IL-15 transfected CD4(+) T cells were more effective in suppressing tumor growth than control retroviral vector transfected ones. To ensure the safety of the method, the employment of thymidine kinase gene made it possible to eliminate these transgenic CD4(+) T cells following ganciclovir treatment. Together, we show that IL-15 transfection induced a selective expansion of antigen-specific CD4(+) T cells ex vivo and enhanced their tumor-suppression effects in vivo. This has an important significance for improving the efficacy of adoptive T cell therapy.