ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Objective: To explore the prevalence of screening myopia and depressive symptom among primary and secondary school students in Xuzhou, and to explore the association of sleep and screen time on the coexistence of screening myopia and depressive symptom, so as to provide scientific references for developing intervention strategies to address the development of myopia and promote mental health in children and adolescents. Methods: From September to October 2024, a stratified cluster random sampling method was used to select 6 605 students in grade 4 to 12 in 2 urban and 2 suburban districts in Xuzhou. The students health condition and influencing factors questionnaire were used to assess students basic information, sleep time, and screen time. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess primary and secondary school students depressive symptom.Unaided distance visual acuity examination was conducted, and refractive assessment was performed using an automated refractometer without cycloplegic agents. The Chi-square test and multiple Logistic regression analysis were used to evaluate the association of sleep and screen time with the coexistence of screening myopia and depressive symptom. Results: The detection rates of screening myopia, depressive symptom, and screening myopia and depressive symptoms co morbidity among primary and secondary school students in Xuzhou were 60.35%, 4.45% and 18.61% respectively. Results from the multinomial Logistic regression analysis, using the healthy group as the reference and after adjusting for confounding factors, showed that students with insufficient sleep duration were more likely to have depressive symptom ( OR=1.57, 95%CI =1.08-2.27) and the coexistence of screening myopia and depressive symptom ( OR=1.85, 95%CI =1.45-2.36). Students with daily screen time≥2 h were more likely to have depressive symptom only ( OR=1.41, 95%CI =1.04-1.93) and the coexistence of screening myopia and depressive symptom ( OR=1.31, 95%CI =1.06-1.61). Further stratified analysis based on sufficient and insufficient sleep duration revealed that only in the insufficient sleep duration group, students with daily screen time≥2 h had an increased risk of depressive symptom only ( OR=1.49, 95%CI =1.07-2.07) and the coexistence of screening positive myopia and depressive symptom ( OR=1.40, 95%CI =1.11- 1.77 ) (all P <0.05). Conclusions Primary and secondary school students with insufficient sleep duration and daily screen time≥2 h have higher risks of depressive symptoms and the coexistence of screening myopia and depressive symptoms. It is recommended to ensure adequate sleep duration and limit screen time for children and adolescents.

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

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

Objective:To evaluate knee biomechanics of patients about 12 months after anterior cruciate ligament(ACL)reconstruction during cutting and determine the abnormal biomechanical characteristics.Methods:Sixteen males about 12 months after ACL reconstruction were recruited for this study.Three-dimensional kinematic and kinetic data were collected during cutting movement.Knee joint angles and moments were calculated.Paired t-tests were used to compare the differences in knee biomechanics be-tween the surgical leg and nonsurgical leg.Results:The peak posterior ground reaction force(surgical leg:0.380±0.071;nonsurgical leg:0.427±0.069,P=0.003)and vertical ground reaction force(surgical leg:1.996±0.202,nonsurgical leg:2.110±0.182,P=0.001)were significantly smaller in the surgical leg than in the nonsurgical leg.When compared with the uninjured leg,the surgical leg demonstrated a smaller knee flexion angle(surgical leg:38.3°±7.4°;nonsurgical leg:42.8°±7.9°,P＜0.001)and larger external rotation angle(surgical leg:10.3°±2.4°;nonsurgical leg:7.7°±2.1°,P=0.008).The surgical leg also demonstrated a smaller peak knee extension moment(surgical leg:0.092±0.031;nonsurgical leg:0.133±0.024,P＜0.001)and peak knee external rotation moment(surgical leg:0.005±0.004;nonsurgical leg:0.008±0.004,P=0.015)when com-pared with the nonsurgical leg.Conclusion:The individuals with ACL reconstruction mainly showed asymmetrical movements in the sagittal and horizontal planes.The surgical leg demonstrated a smaller peak knee flexion angle,knee extension moment,and knee external rotation moment,with greater knee external rotation angle.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Objective To investigate the effects of granulocyte colony-stimulating factor(G-CSF)combined with tadalafil(TD)on endometrial receptivity and pregnancy outcomes in patients with thin endometrium(TE).Methods Patients with TE in the department of reproductive medicine of the First Hospital of Qinhuangdao from May 2020 to March 2023 were selected as the study subjects.They were divided into a experimental group(G-GSF combined with TD)and a control group(G-GSF)according to the different treatment regimens.The endometrial receptivity[endometrial thickness(EMT),endometrial volume(EMV),endometrial blood flow peak systolic flow rate/end diastolic flow rate(EBF-S/D),endometrial fractionation,endometrial blood flow fractionation,uterine artery pulsatility index(AUPI),uterine artery resistance index(AURI)and uterine arterial peak systolic flow rate/end diastolic flow rate(AU-S/D)]of the TE patients before and after treatment(the endometrial transition day)were compared;the endometrial receptivity on endometrial transformation day,post-treatment pregnancy outcomes[embryo implantation rate(EIR),clinical pregnancy rate(CPR),and early miscarriage rate(ABR)],and the incidence of adverse reactions during treatment were compared between the two groups.Results A total of 60 patients were included in the study,with 30 in each group.Before treatment,the difference in endometrial receptivity between the two groups was not statistically significant(P＞0.05).Compared with the pre-treatment period,the EMT,EMV,the proportion of type A endometrium and the proportion of type Ⅱ+Ⅲ endometrial blood flow significantly increased in the two groups after treatment on the endometrial transformation day increased significantly(P＜0.05),while the EBF-S/D,AUPI,AURI and AU-S/D significantly decreased(P＜0.05).EMT and EMV were greater in the experimental group than in the control group(P＜0.05),whereas EBF-S/D,AUPI,AURI and AU-S/D were less than those in the control group(P＜0.05).Compared with the control group,the differences in the proportion of endometrium,the proportion of endometrial blood flow,EIR,CPR and ABR in the experimental group were not statistically significant(P＞0.05).No adverse reactions occurred during treatment in both groups.Conclusion G-CSF combined with TD can improve endometrial receptivity in TE patients with high safety,but there is no effect on pregnancy outcome.