Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective: To understand the association between weight-adjusted-waist index (WWI) and cardiopulmonary endurance among middle school students, so as to provide references for the improvement of cardiopulmonary endurance levels in adolescents. Methods: From June 2015 to December 2018 by using the method of purposive sampling, height, weight, waist circumference, and 20 m shuttle-run tests were measured among 44 870 adolescents aged 13-18 from Northeast, North, East, South, Southwest and Northwest of China. The WWI of the adolescents and the maximum oxygen uptake (VO 2max ) were calculated indirectly. The t-test and one way analysis of variance were used for comparison, and the curve regression analysis method was adopted to analyze the relationship between WWI and VO 2max . Results: For Chinese middle school students aged 13-18, the WWI was (9.35±1.02), the number of 20 m shuttle-run was (38.89±18.14) times, and VO 2max was (39.96±5.88) mL/(kg ·min -1 ). The differences of VO 2max between WWI quartile arrays of boys aged 13-18 were statistically significant ( F=15.19, 9.00, 14.97, 20.48, 28.13, 10.13 , P <0.01), girls had the same trend ( F=23.36, 16.61, 33.45, 32.96, 18.23, 19.36, P <0.01). There was an inverted U shaped curve relationship between WWI and cardiopulmonary endurance. When WWI was 8.5, the VO 2max level reached the highest, which was 40.07 mL/(kg ·min -1 ). Compared with girls, WWI in boys had a more significant impact on cardiopulmonary endurance. Conclusion Maintaining optimal WWI levels may enhance adolescents cardiopulmonary endurance.

Objective: To explore the relationship between sleep quality and mental health among middle school students, so as to provide scientific basis for improving mental health among adolescents. Methods: From September to December 2023, a stratified cluster random sampling method was employed to select 5 713 middle school students aged 13-18 from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi, and Urumqi. Sleep quality and mental health were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Brief Adolescent Mental Health Assessment Questionnaire. Spearman correlation analysis and linear regression analysis were used to explore the relationship between sleep quality and various dimensions of mental health among middle school students. Results: There was a statistically significant difference in the total PSQI score among middle school students of different age groups ( H=226.49, P <0.01), and there was no statistically significant difference in the psychological health scores of middle school students in different age groups ( H=5.37, P >0.05). In terms of gender, the total PSQI score for girls [5.00 (3.00, 6.00)] was higher than that for boys [4.00 (2.00, 6.00)]; additionally, boys had higher mental health scores [85.00 (75.00, 90.00)] than females [83.00 (70.00, 89.00)], with statistically significant differences ( Z=-10.90, -8.16, P <0.01). Spearman correlation analysis revealed a negative correlation between total PSQI scores and mental health scores ( r=-0.51, P <0.05) among middle school students. After controlling for variables such as maximum oxygen uptake, physical activity and nutritional status, linear regression analysis further confirmed that higher PSQI scores were associated with lower mental health scores ( B=-3.76, 95%CI = -4.15 to -3.38, P <0.01). Conclusion There is a negative correlation between PSQI scores and mental health scores among middle school students, indicating that improving sleep quality may contribute to better mental health among middle school students.

Objective: To explore the relationship between sleep quality and executive function among middle school students, so as to provide theoretical support for the promotion of adolescents physical and mental health development. Methods: From September to December 2023, 5 713 junior and senior high school students aged 13 to 18 were selected by stratified cluster random sampling method from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi, and Urumqi. Pittsburgh Sleep Quality Index was used to conduct sleep quality survey. And conduct executive function was tested on middle school students, including inhibitory function, refresh function and conversion function tests. Spearman correlation and linear regression were used to analyze the relationship between sleep quality and executive function of middle school students. Results: The total Pittsburgh Sleep Quality Index (PSQI) score of boys was [4.0(2.0,6.0)] and that of girls was [5.0(3.0,6.0)], and the difference was statistically significant ( Z=-10.90, P < 0.01 ). The total PSQI score of boys was positively correlated with both 2-back reaction time and conversion function of executive function ( r =0.04, 0.04); the total PSQI score of girls was negatively correlated with 2-back reaction time ( r =-0.04) ( P <0.05). After controlling for variables such as mental health, physical activity and nutritional status,linear regression analyses showed that PSQI total score of middle school students was positively correlated with the inhibitory function and the conversion function response time [ B (95% CI )=1.28(0.21-2.34), 7.62(2.34-12.90), P <0.05]; the associations of total PSQI scores among middle school students with both 2-back and 1-back response time were not statistically significant [ B (95% CI )=-5.88(-16.14-4.37), 8.05( -3.39 -19.50), P >0.05]. Conclusion Positive correlations are observed on sleep quality with inhibitory and conversion functions of executive function among middle school students.

Objective: To explore relationship of sleep quality with overweight and obesity among middle school students, so as to provide a reference basis for improving adolescent sleep health. Methods: From September to December 2023, 5 713 middle school students aged 13 to 18 were selected by stratified cluster random sampling method in six regions, including Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi. Sleep quality survey was conducted on middle school students by Pittsburgh Sleep Quality Index. Height and weight were measured, and World Health Organization s standards for growth and development of children and adolescents was used to evaluate their nutritional status. Both χ 2 test and Logistic regression analysis were used to analyze the association between sleep quality and nutritional status of middle school students. Results: The non compliance detection rate of sleep quality was 38.4% among girls, but 29.2% among boys, and the difference was of statistical significance( χ 2=54.08, P < 0.01 ). The detection rate of substandard sleep quality was 34.2% in the group with normal nutritional status, 38.3% in the group with overweight, 43.7% in the group with obesity and 26.0% in the group with emaciation, and the difference in the rates of substandard sleep quality among middle school students of different nutritional status was statistically significant ( χ 2=68.15, P <0.01). Logistic regression analysis showed that, after controlling for mental health and physical activity, the detection rate of substandard sleep quality in the obese groups was 1.30 times higher than that in the normal group, respectively( OR =1.30, 95% CI =1.06- 1.59 , P <0.01). Conclusions Sleep quality is correlated with overweight and obesity among middle school students, and there are gender differences. Intervention policies should be formulated according to the characteristics of different genders.

Objective: To explore the association between physical activity and sleep quality among middle school students, so as to provide reference for adolescent sleep improvement. Methods: From September to December 2023, 5 713 middle school students aged 13-18 years were selected from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi by stratified cluster random sampling method. Pittsburgh Sleep Quality Index (PSQI) and Evaluation of Physical Activity Levels of Children and Adolescents Aged 7-18 Years were used to investigate and evaluate sleep quality and physical activity. Comparisons between groups were made using the t-test, Mann-Whitney U-test, and associations between physical activity and sleep quality of middle school students were analyzed using Spearman correlation and linear regression methods. Results: The total PSQI scores were 4.0(2.0,6.0) and 5.0 (3.0,6.0) for boys and girls, respectively, with significant sex difference ( Z =-10.90, P <0.01); light physical activity(LPA) and moderate to vigorous physical activity(MVPA) of boys were 18.57 (2.86, 42.86) and 68.57 (35.71, 119.18)min, and girls were 14.29 (0.00, 30.00) and 55.71 (31.43, 92.86)min respectively, and the differences were statistically significant ( Z =3.65, -8.65 , P <0.01). The results of Spearman correlation regression showed that adolescents MVPA was negatively correlated with the total PSQI score ( r =-0.04, P <0.01). After controlling for variables such as mental health, nutritional status and maximum oxygen uptake, the results of linear regression analysis showed that PSQI total score negatively predicted MVPA among middle school students ( B =-4.76, 95% CI =-7.16 to -2.36, P <0.05). Conclusion The longer the duration of physical activity among middle school students, the better the quality of sleep.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To investigate the brain activity and related hypoxic indicators in early cognitive processing stage (200-600 ms) and late cognitive processing stage (600-1 000 ms) by comparing their cognitive processing in pilots performed classical Stroop task under hypoxic state.Methods:Fifteen male Air Force pilots who were qualified in aeromedical assessment were selected. The behavioral indicators (accuracy, response time), event related potentials (ERP) component metrics (N2), and spectral metrics (Alpha band, Beta band) were monitored and analyzed when the pilots complete the cognitive conflict control task in the simulated 5 000 m hypoxic state and normal state.Results:The main effect of relationship type factors in response time indicators was significant ( F=4.10, P=0.027), and no difference found in accuracy indicators (all P>0.05). The reaction time under conflict conditions was (543.360±21.202) ms, which was higher than the reaction time under consistent conditions (509.078±14.420) ms, and the difference was significant ( F=3.28, P=0.039). The reaction time under unrelated conditions was (521.697±15.073) ms, and there was no significant difference between the reaction time under consistent and conflicting conditions (all P>0.05). Hypoxic status resulted in a significant increases in early stage indicator N2 amplitude ( F=5.34, P=0.037), and the power of Alpha, Low beta and Mid beta of late stage ( F=7.76, 5.34, 4.92, P=0.015, 0.037, 0.044). Conclusions:The amplitude of N2 can be used as the ERP indicator to investigate the pilots′ brain activities at the early stage of cognitive processing under hypoxia state; Alpha, Low beta and Mid beta bands of the spectrum can be used as the indicators to evaluate the brain activity of pilots in the late stage of cognitive processing under hypoxia state, which can be used in the training evaluation of pilots to provide more objective physiological data to improve the training effect of pilots.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.