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

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

Based on the Delphi method, combined with the results of the previous literature study and expert interviews, 3 rounds of expert consultation were conducted to evaluate the degree of concentration of expert opinions and their importance from 3 aspects: arithmetic mean, full score ratio ( Ki), and rank sum ( Si), to construct a diagnostic scale for rheumatoid arthritis (RA) cold-dampness syndrome. In this study, 30 expert questionnaires were distributed in the 1st round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.309; 30 expert questionnaires were distributed in the 2nd round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.320; and 30 expert questionnaires were distributed in the 3rd round, 29 questionnaires were recovered, and the expert coordination coefficient was 0.387. The maximum value of the coefficient of variation of the experts of the 3 rounds was 0.27, and the minimum value was 0.09, suggesting that the consistency and credibility of the experts' evaluation of the importance of the entries of cold-dampness syndrome were high. In this study, the mean values and weights of 17 entries were finally obtained, of which the top 5 entries were cold pain in joints (4.793, 0.066 6); aggravated by cold (4.586, 0.063 7); white tongue coating (4.552, 0.063 2); aggravated in cloudy and rainy days (4.448, 0.061 8); and painful joints that are not warm to the touch (4.379, 0.060 8). This study completed the screening of relevant entries and conducted preliminary discussions, laying the foundation for constructing a diagnostic scale for RA cold-dampness syndrome and forming the final diagnostic criteria. The research method is scientific and reliable, which can provide reference for the diagnostic standard of RA cold-dampness syndrome, but further clinical practice research is still needed.

Objective: To explore the mediating effect of anxiety, insomnia, and family cohesion between Internet addiction and non suicidal self injury (NSSI) behavior among junior and senior school students, so as to develop interventions to promote adolescent mental health. Methods: A total of 3 026 junior and senior school students from Yixing, Jiangsu Province, China, were selected by stratified cluster sampling from December 2022 to February 2023, and were administered the Ottawa Self injury Inventory (OSI), Depression, Anxiety and Stress Scale-21 (DASS-21), Family Environment Scale-Chinese Version (FES-CV), Insomnia Severity Index (ISI), and Chinese Internet Addiction Scale Revised (CIAS-R). A mediating effect model was constructed to analyze the mediating effect of anxiety, insomnia, and family cohesion on Internet addiction and NSSI. Results: Internet addiction ( r = 0.24), insomnia ( r =0.28), and anxiety ( r =0.27) were positively correlated with NSSI, while the latter was negatively correlated with family cohesion ( r =-0.23) ( P <0.01). The mediating effect model was well fitted ( CFI=0.999, TLI=0.978, RMSEA = 0.030 ). Anxiety (mediation effect value:0.12, 95% CI =0.08-0.18) and family cohesion (mediation effect value:0.08, 95% CI = 0.03 -0.13) had a separate mediating effect. A chain meditating effect was found in the case of anxiety and insomnia (mediation effect value:0.14, 95% CI =0.10-0.20), family cohesion and anxiety (mediation effect value:0.05, 95% CI =0.03-0.07), family cohesion and insomnia (mediation effect value:0.05, 95% CI =0.03-0.07), and family cohesion, anxiety, and insomnia (mediation effect value:0.06, 95% CI =0.04-0.08). The mediating effect accounted for 14.9%, 10.1%, 17.5%, 6.0%, 5.6%, and 7.1%, respectively. Conclusions Anxiety, insomnia, and family cohesion partially mediate Internet addiction and NSSI. Schools and families should pay attention to Internet addiction among junior and senior school students and develop appropriate interventions to promote adolescent mental health, so as to reduce the prevalence of NSSI.

Objective: To explore the association between negative emotion (depression, anxiety and stress), family intimacy and Internet addiction, so as to provide a basis for the intervention of Internet addiction among junior and senior high school students. Methods: Students were selected by stratified random cluster sampling method from junior high schools and senior high schools from December 2022 to February 2023 in Yixing City, Jiangsu Provicne. A total of 3 026 students completed the questionnaire survey, including the demographic characteristics, Depression, Anxiety and Stress Scale-21 (DASS-21), Family Environment Scale-Chinese Version (FES-CV), and Chinese Internet Addiction Scale Revised (CIAS-R). Bivariate correlation was used to analyzed the association of family intimacy, depression, anxiety, stress, and Internet addiction. Mediating effect model was used to analyzed the mediating effect of negative emotion between family intimacy and Internet addiction. Results: The average score of Internet addiction among junior and senior high school students was (46.26±15.58), and there were statistical differences in the average scores of Internet addiction across different grades ( F=87.15, P <0.01). Depression ( r =0.57), anxiety ( r =0.56), stress ( r = 0.57) were positively correlated with Internet addiction, and family intimacy ( r =-0.34) was negatively correlated with Internet diction ( P <0.01). In the mediating effect model, family intimacy negatively predicted negative emotion ( β =-0.48) and Internet addiction ( β =-0.10), and negative emotion positively predicted Internet addiction ( β =0.45) ( P <0.01). Negative emotion played a partial mediating role between family intimacy and Internet addiction (the mediation value:-1.71, 95% CI =-1.96--1.49, mediation ratio:67.9%, P <0.05). Conclusions There are associations between negative emotion, family intimacy and Internet addiction among junior and senior school students. Family intimacy indirectly affects Internet addiction mainly through negative emotion. It suggests that family education is in need of attention to reduce the prevalence rate of Internet addiction among junior and senior high school students, especially family intimacy.

Objective: To understand different types of depression and anxiety among primary and secondary school students, as well as their influencing factors, so as to provide a basis for the development of future intervention programs for adolescent mental health. Methods: From December 2022 to February 2023, a self administered questionnaire survey was administered among grades 4 to 6 students and junior school, senior school students in Yixing City using Depression Anxiety and Stress Scale-21 (DASS-21), Insomnia Severity Index (ISI), Family Environment Scale (FES), and modified Yale Food Addiction Scale 2.0 (mYFAS 2.0), Ottawa Self injury Inventory (OSI). A total of 4 180 students were included in the analysis. Different types of depression and anxiety in students and their influencing factors were analyzed by the Chi squaretest and multivariate Logistic regression. Results: The overall prevalence of depression and anxiety among primary and secondary school students were 16.6% and 22.4%, respectively, with 14.0% of depression and anxiety comorbidities. The Logistic regression results showed that, compared to students with low depression-low anxiety, students of depression and anxiety who had parents in conflicts ( OR =3.06), smoked ( OR =3.16), exhibited moderate food addiction ( OR =3.56), and had non suicidal self injury (NSSI) ( OR =2.26) were more likely to be classified as a depression predominant-depression anxiety type. Students of depression and anxiety who consumed alcohol ( OR =2.00), had serious food addiction ( OR =5.44), moderate to severe insomnia ( OR =3.25), and mild insomnia ( OR =1.88) were more likely to be classified as anxiety predominant-depression anxiety type. Students of depression and anxiety with low mood ( OR =10.87), mild food addiction ( OR =2.00), moderate food addiction ( OR =4.32), and severe food addiction ( OR =7.35), mild ( OR =2.96) or moderate to severe ( OR =16.52) insomnia, and NSSI ( OR =4.24) were more likely to be classified as the severe depression anxiety type( P < 0.05 ). Conclusions There are significant differences between different depression-anxiety types among primary and secondary school students with respect to food addiction, insomnia, NSSI, smoking, and alcohol use. Relevant departments should engage with schools and families to adopt targeted interventions for students to reduce the occurrence of mental health problems.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

The aquatic grass Zizania latifolia grows symbiotically with the fungus Ustilago esculenta producing swollen structures called Jiaobai, widely cultivated in China. A new disease of Z. latifolia was found in Zhejiang Province, China. Initial lesions appeared on the leaf sheaths or sometimes on the leaves near the leaf sheaths. The lesions extended along the axis of the leaf shoots and formed long brown to dark brown streaks from the leaf sheath to the leaf, causing sheath rot and death of entire leaves on young plants. The pathogen was isolated and identified as the bacterium Pantoea ananatis, based on 16S ribosomal RNA (rRNA) gene sequencing, multilocus sequence analysis (atpD (β-subunit of ATP synthase F1), gyrB (DNA gyrase subunit B), infB (translation initiation factor 2), and rpoB (β‍-subunit of RNA polymerase) genes), and pathogenicity tests. Ultrastructural observations using scanning electron microscopy revealed that the bacterial cells colonized the vascular tissues in leaf sheaths, forming biofilms on the inner surface of vessel walls, and extended between vessel elements via the perforated plates. To achieve efficient detection and diagnosis of P. ananatis, species-specific primer pairs were designed and validated by testing closely related and unrelated species and diseased tissues of Z. latifolia. This is the first report of bacterial sheath rot disease of Z. latifolia caused by P. ananatis in China.
Pantoea/genetics* ; Plant Diseases/microbiology* ; Poaceae/microbiology* ; Virulence