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

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To investigate the expression level and clinical significance of circular RNAs(circRNAs)in serum extracellular vesicles(EVs)of patients with recurrent spontaneous abortion(RSA).Methods The serum samples from 3 RSA patients and 3 nor-mal pregnant women(controls)visited our hospital from May 2021 to March 2023 were collected and the gene expression profiling chips were used to screen for differentially expressed circRNAs in serum EVs.Ten RSA patients and 10 normal pregnant women were enrolled in a training set and 80 RSA patients and 64 normal pregnant women were enrolled in a validation set.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of differentially expressed circRNAs between the two groups.The predictive value of differentially expressed circRNAs for RSA was evaluated by the receiver operating characteristic(ROC)curve.Results A total of 57 563 circRNAs in serum EVs were detected by the gene expression profiling chips.Compared with the control group,3 516 circRNAs were differentially expressed in RSA patients,including 2 377 up-regulated and 1 139 down-regulated.The de-tection results of qRT-PCR in the training set and validation set showed that the expression levels of hsa＿circ＿0054403 in serum EVs of RSA patients(2.07[1.00,6.68])was significantly higher than that in the control group(1.00[0.42,1.46],U=1 239,P＜0.01),while those of hsa＿circ＿0020897(0.33[0.11,1.40]vs 1.00[0.46,3.66],U=1 712,P＜0.01)and hsa＿circ＿0072745(0.49[0.22,1.60]vs 1.00[0.51,7.93],U=1 714,P＜0.01)were significantly lower than that in the control group.The ROC curve showed that the hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs had high predictive value for RSA.Their AUCROC were 0.758,0.666,and 0.664,respectively,and the corresponding sensitivity and specificity were 47.5% and 100.0%,50.0% and 81.2%,and 62.5% and 70.3%,respectively.When the three circRNAs were combined,it's AUCROC,sensitivity,and specificity were 0.842,73.7%,and 79.7%,respectively.Conclusion The hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs of RSA patients are abnormally expressed,which may serve as the potential markers for predicting RSA.

Objective:To develop and validate a risk prediction model for hospital discharge readiness in patients undergoing surgery for Stanford type B aortic dissection (TBAD) .Methods:A total of 130 patients who underwent TBAD surgery at Taizhou Hospital of Zhejiang Province between January 2020 and September 2024 were recruited by convenience sampling and divided into a training set ( n=91) and a validation set ( n=39) at a 7∶3 ratio. Readiness for hospital discharge was assessed using the Chinese version of the Readiness for Hospital Discharge Scale, and patients were categorized into good and poor readiness groups. Univariate analysis was used to compare demographic and disease-related data as well as admission Aortic Dissection Detection Risk Score (ADD-RS) between groups. Logistic regression was employed to identify factors influencing discharge readiness. A nomogram was developed using R software, and its predictive performance was evaluated with receiver operating characteristic (ROC) curves. Calibration curves and decision curve analysis (DCA) were further used to assess the accuracy and clinical utility of the model. Results:Logistic regression identified feedback-based health education, number of hospitalizations, ADD-RS score, emergency surgery, and length of hospital stay as independent predictors of discharge readiness. ROC curve analysis showed that the area under the curve ( AUC) for predicting poor discharge readiness was 0.91 [95% CI (0.85, 0.97) ] in the training set and 0.84 [95% CI (0.80, 0.99) ] in the validation set. Calibration curves and the Hosmer-Lemeshow test confirmed good calibration in both sets ( P>0.05). DCA demonstrated significant net clinical benefit when the high-risk threshold exceeded 0.02, although the benefit decreased as the threshold approached 0.80. Conclusions:The risk prediction model developed in this study effectively predicts poor discharge readiness in patients after TBAD surgery, showing good discrimination and calibration. The identified risk factors provide targeted directions for clinical interventions, which may help improve patients' readiness for discharge.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.