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

Aim To investigate the effect of discoidin domain receptor 1(DDR1)on high glucose induced endothelial cell dysfunction and the underlying mecha-nism.Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided in-to the control group and high glucose induction group(HG).HUVECs were treated with 33 mmol·L-1 D-glucose for 48 hours to construct endothelial dysfunc-tion.Pyroptosis was detected using propidium iodide staining(PI);lactate dehydrogenase(LDH)and IL-1β,IL-18 levels were determined using enzyme linked immunosorbent assay(ELISA);the expression of DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related proteinses were detected using Western blot.Subsequently,the experiment was divid-ed into the control group,HG group,HG+DDR1 NC group,and HG+DDR1 siRNA group.The effect of high glucose on the proliferation and migration of HU-VECs was observed after transfection with DDR1 siR-NA for 24 hours;ELISA was used to detect the endo-thelial nitric oxide synthase(eNOS),vascular cell ad-hesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),as well as LDH,IL-1β,IL-18 levels;PI was employed to detect pyroptosis;Western blot was applied to detect DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related pro-teins.Results Compared with the control group,HG group decreased eNOS content,increased VCAM-1 and ICAM-1 contents,decreased cell viability and migration ability,and significantly increased the expressions of DDR1,p-NF-κB,NLRP3 and pyroptosis related pro-teins.The levels of LDH,IL-1β,IL-18 and the rate of pyroptosis significantly increased(P＜0.05).Com-pared with HG group,DDR1 siRNA could promote the secretion of eNOS,decrease the levels of VCAM-1,ICAM-1,LDH,IL-1β and IL-1 8,increase cell viability and migration ability,reduce the expression of p-NF-κB,NLRP3 and pyroptosis related proteins,and inhibit high glucose-induced pyroptosis of HUVECs(P＜0.05).Conclusions Gene silencing DDR1 can im-prove vascular endothelial cell dysfunction induced by high glucose,and the mechanism is related to the inhi-bition of NF-κB/NLRP3 signaling pathway mediated pyroptosis.

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy

Humans ; Microscopy ; Vocal Cords

ObjectiveTo explore the effects of Wumeisan on gut lactase activity and microflora diversity of mice with dysbacteriosis diarrhea. MethodThe mice were randomly divided into 4 groups， namely， the normal group， the model group， and the low-dose and high-dose Wumeisan groups， with 8 mice in each group. The mouse model was made by gavage of mixed antibiotics for 7 d， and the low-dose and high-dose Wumeisan groups （5.98， 11.96 g·kg^-1） were given gavage for 7 d continuously. The normal group and the model group were given the same volume of sterile water. The changes in the body weight， food intake， and diarrhea of mice were recorded. Feces were collected after the last administration， and the lactase activity was detected by the colorimetric method. The gut microbiota changes were detected by the 16S rRNA high-throughput sequencing technology. ResultCompared with those in the normal group， the mice in the model group had dilute and soft stools， reduced body mass， reduced food intake， reduced lactase activity， significantly reduced intestinal flora diversity， and significant changes in the relative abundance phylum and genus levels of flora. Compared with the model group， Wumeisan reduced the diarrhea rate of mice， promoted the rapid recovery of body weight and food intake， increased the lactase activity decreased by antibiotic， improved the community abundance and diversity of mice with dysbacteriosis， and made the species composition closer to that in the normal group. The abundance of three phyla （Bacteroidota， Proteobacteria， Verrucomicrobiota） and nine genera （Odoribacter， Enterococcus， Clostridium innocuum group， etc.） of mice with diarrhea were regulated by Wumeisan. Among them， norank f Muribaculaceae， norank f norank o Clostridia UCG-014， Lachnospiraceae NK4A136 group， and Odoribacter showed significant positive correlation with the body weight and lactase activity， and Escherichia-Shigella， Enterobacter， Enterococcus， and Clostridium innocuum group showed significant positive correlation with the diarrhea rate. Function prediction showed that the high-dose Wumeisan significantly reseted 6 functional levels of metabolism， genetic information processing， and human diseases， and had positive effects on endocrine and metabolic diseases， immune diseases， infectious disease， and parasitic infectious diseases. ConclusionWumeisan can relieve the symptoms of dysbacteriological diarrhea by increasing the lactase activity and regulating the gut microbiota composition.

Objective: To explore the effect of three interventions including caloric restriction, rope-skipping exercise and caloric restriction combined with rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students. Methods: This study was a pilot randomized controlled trial. Overweight or obese students who met the inclusion criteria were recruited at Sun Yat-sen University in September 2019 and were randomly divided into four groups: caloric restriction group (CR), rope-skipping group (RS), combined group (CR-RS) and control group (CT). The intervention in each group lasted 8 weeks, specifically: the daily energy intake of CR was 100% to 110% of the basal metabolic energy; RS was instructed to rope three times a week, and CR-RS combined caloric restriction with rope-skipping. At the baseline and end of 8-week intervention, basic information, anthropometric indicators and fasting vein blood of students were collected. Paired t test and Wilcoxon paired-samples signed rank test were used for comparison before and after intervention, and analysis of covariance was used for comparison between groups after intervention. Results: A total of 29 students completed the trial and were included in the final analysis (7, 9, 7 and 6 students in CR, RS, CR-RS and CT, respectively). The mean age of students were (19.00±1.00) years, including 11 males and 18 females. The baseline characteristics of four groups were comparable. After 8 weeks of intervention, compared with CT, there was an increase in the body fat percentage and fat mass index in CR and CR-RS (P<0.05). Insulin level decreased in CR-RS (P<0.05). Systolic blood pressure in CR and diastolic blood pressure in CR-RS were higher (P<0.05). Compared with baseline, fat mass index decreased in CR (P<0.05), while body weight, BMI, and fat mass index decreased in CR-RS (P<0.05). Conclusion: It is suggested that the caloric restriction alone and calorie restriction combined with rope-skipping exercise can benefit overweight or obese college students with cardiometabolic risk factors.
Adolescent ; Adult ; Caloric Restriction ; Cardiometabolic Risk Factors ; Female ; Humans ; Insulins ; Male ; Obesity ; Overweight ; Students ; Weight Loss/physiology* ; Young Adult

ObjectiveTo evaluate the ABHD5 expression in pan-cancer and its correlations with the main clinical stages， prognosis and immune cell infiltration. MethodsGTEx， TCGA， TIMER2.0， CPTAC databases， immunohistochemistry and western blot were used to analyze the expression levels of ABHD5 in different cancer tissues and adjacent tissues as well as correlations between ABHD5 expression and the main clinical stages. Kaplan-Meier Plotter， Oncolnc and R2 databases were used to explore the prognostic value of ABHD5. The relationship between ABHD5 and immune cell infiltration was analyzed by TCGA and TIMER2.0 databases. STRING and GEPIA databases were used to detect ABHD5-binding proteins and co-expression genes， which were then analyzed by GO and KEGG. ResultsThe mRNA and protein expression levels of ABHD5 were lower in cancer tissues than those in normal tissues in multiple cancer types， but higher in few cancer types. High-level expression of ABHD5 was related to better prognosis in 8 cancer types and related to worse prognosis in 2. ABHD5 expression levels were positively correlated with immune cell infiltration in 9 cancer types， and were the same with neutrophil infiltration and expression of immune checkpoints in pan-cancer. Enrichment analysis showed that ABHD5 was related to histone demethylation. ConclusionPossibly used as a potential prognostic predictor in pan-cancer， ABHD5 was also correlated with neutrophil infiltration， expression of immune checkpoints and histone demethylation.

Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

SARS-CoV-2 can cause multiple organ injuries in some susceptible people in a short time, which seriously threatens the health and safety of people, and intensive care and multiple extracorporeal organ support are important means of treatment. Although many experts’ consensus and clinical guidelines have been published, a series of clinical problemsstill exist during the treatment procedure, and no consensushas not been reached until now. Therefore,in this paper wemake some reflections and explorations to provide experience and help for clinicians.

【Objective】 To investigate the expression and significance of phosphorylated receptor tyrosine kinase(p-AXL) in diffuse large B cell lymphoma(DLBCL), and the clinical value of its co-expression with BCL-2 and /or c-MYC split gene. 【Methods】 Totally 118 cases of DLBCL were collected in the First Affiliated Hospital of Sun Yat-sen University from 2012 to 2017, and prepared as tissue array. p-AXL, c-MYC and BCL-2 proteins were detected by immunohistochemistry, and c-MYC split gene was detected by FISH staining. 【Results】 p-AXL protein was stained on tumor cells’membrane or in the cytoplasm of DLBCL cells. p-AXL was expressed more commonly in Non-GCB type than in GCB type. The expression of p-AXL was significantly correlated with the chemotherapy effect(P<0.01), and the expression of c-MYC split gene or BCL-2 protein separately(P<0.01). Co-expression of p-AXL and c-MYC, or BCL-2, or both of them was significantly correlated with the Hans typing(P<0.01). The PFS of p-AXL positive patients was obviously lower than that of p-AXL negative patients(P<0.05). The OS of p-AXL positive patients was also lower than that of the negative patients, but the difference had no statistical significance(P>0.05). Univariate analysis showed that p-AXL and male, p-AXL and Non-GCB type, p-AXL and c-MYC co-expression, p-AXL and c-MYC and/or BCL-2 co-expression were the risk factors for PFS and OS in DLBCL patients(P<0.05). Multivariate analysis showed that p-AXL positive in male(P<0.05) and p-AXL/c-MYC co-expression(P<0.01) were independent risk factors for PFS and OS in DLBCL patients. 【Conclusions】 p-AXL protein is expressed in DLBCL, and its expression is significantly related to the expression of c-MYC and BCL-2. p-AXL expression is associated with lower chemotherapy response rate, shorter progression-free survival and shorter overall survival. p-AXL/c-MYC co-expression or p-AXL positive in male may be an independent prognostic factor for DLBCL patients.