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

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective To construct a TCM Zhengsu differentiation model for type 2 diabetes based on deep learning and multimodal fusion,thus providing algorithmic support for full intelligence in TCM Zhengsu differentiation.Methods A total of 2585 patients with type 2 diabetes were recruited.Three experts were invited to perform the Zhengsu differentiation separately.Deep fully connected neural networks,U2-Net and ResNet34 networks were applied to construct the symptom-based differentiation model(S-Model)and the tongue image-based differentiation model(T-Model),respectively,while multimodal fusion techniques were employed to build the multimodal fusion model(TS-Model)with the above two as co-inputs.Finally,the prediction performance of the above models was compared by F1 value,accuracy,and recall.Results The predicted F1 values of the T-Model fluctuated from 0.000%to 86.726%,while those in the S-Model and TS-Model fluctuated from 0.000%to 97.826%and from 55.556%to 99.065%,respectively.A stable and high F1 value was found in the TS-Model.Conclusion The multimodal fusion technique was demonstrated to be applicable in the TCM Zhengsu differentiation model,which provided methodological support for developingof a fully intelligent Zhengsu differentiation model with high objective four diagnostic information.

Retinopathy of prematurity(ROP)is a retinal vascular proliferative disease that occurs in preterm low-birth-weight infants and is the leading cause of blindness in children worldwide.Currently,with the intensive study of ROP,it has been found that retinal neovascularization can spontaneously regress at any time in the early stages of the disease.Therefore,early screening,diagnosis and intervention are particularly important in children with ROP.However,the exist-ing screening methods have problems such as long screening times and poor cooperation of infants and children,which may lead to missed diagnoses,thus more reliable prediction methods are needed.This article briefly describes the screening and prediction methods for ROP at home and abroad in recent years,and systematically analyzes the predictive value of different types of biomarkers for ROP,with a view to providing a basis for establishing a reasonable prediction model for ROP.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.

Objective:To understand the gene characteristics of Sapovirus from diarrhea cases in diarrhoeal disease clinics in Beijing.Methods:In 2019, stool samples were collected from diarrhea cases in diarrhoeal disease clinics in Beijing. The samples were used for the detection of nucleic acid of Sapovirus with real-time RT-PCR. Different RT-PCR methods were used for the partial gene segment amplification in the capsid protein VP1 region and the polymerase RdRp region, and sequencing was conducted for amplified positive products. The sequences were aligned with software BioEdit 7.0.9.0 and analyzed with software Mega 6.06.Results:The overall detection rate of Sapovirus was 2.89% (44/1 522), the detection rate in children under 5 years old was 3.34% (18/539) and 2.64% (26/983) in children aged ≥5 years. The capsid protein VP1 region was sequenced in 23 strains belonging to 8 genotypes (GⅠ.2 had 6 strains, GⅠ.1 and GⅡ.3 had 5 strains, respectively, GⅠ.3 and GⅡ.5 had 2 strains, respectively, GⅠ.5, GⅡ.1 and GⅣ.1 had 1 strain, respectively). A total of 16 strains were detected in the cases aged ≥5 years, and the proportion of GⅠ.2 was highest (37.50%, 6/16), and 7 strains were detected in the cases under 5 years old, the proportions of GⅠ.1 and GⅡ.3 were highest (both 42.86%, 3/7); The internal similarity of each genotype was 95.5%-100.0%, and the similarity with the 51 reference strains of human or sewage sources in different years and different countries was 92.2%-100.0%. The polymerase RdRp region was sequenced in 25 strains belonging to 8 genotypes (GⅡ.P3 had 9 strains, GⅠ.P3 had 4 strains, GⅠ.P1, GⅠ.P2 and GⅡ.P1 had 3 strains, respectively, GⅠ.P5, GⅡ.P5 and GⅣ.P1 had 1 strain, respectively). Fifteen strains were detected in the cases aged ≥5 years, and GⅡ.P3 had the highest proportion (40.00%, 6/15). Ten strains were detected in the cases under 5 years old, and the proportions of GⅠ. P1, GⅡ.P1 and GⅡ.P3 were highest (all 30.00%, 3/10); The internal similarity of each genotype was 94.0%-100.0%, and the similarity with the 39 reference strains of human or sewage sources in different years and different countries was 90.2%-99.1%.Conclusions:Sapovirus is one of the pathogens among diarrhea cases in Beijing. The main genome is GⅠ and GⅡ, and the genotypes are diverse and dispersed. The main genotypes of diarrhea cases in people aged ≥5 years and less than 5 years are different.

Objective:To investigate serum lipidomic profiles in patients with chronic actinic dermatitis (CAD), and to search for biomarkers of CAD.Methods:A retrospective analysis was conducted. Serum samples were collected from 46 patients with CAD and 16 age- and gender-matched healthy controls in the Guangzhou Institute of Dermatology from April 2011 to December 2021. Changes in serum lipid composition and expression were assessed by liquid chromatography-mass spectrometry. Principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis were performed to screen differential biomarkers, and receiver operating characteristic (ROC) curve analysis was conducted to screen diagnostic markers. Comparisons of the age and gender distribution between groups were performed using t test and chi-square test, respectively. Results:The 46 CAD patients were aged from 30 to 84 (60.39 ± 10.52) years, including 41 males and 5 females; the 16 healthy controls were aged from 50 to 89 (59.81 ± 10.72) years, including 14 males and 2 females; there were no significant differences in the age or gender distribution between the two groups (age: t = 0.19, P = 0.853; gender: χ2 = 0.03, P = 0.859). Totally, 4 136 lipid molecules belonging to 40 subclasses were identified in the serum samples from CAD patients as well as healthy controls. Twenty-two differential lipid molecules were identified between the CAD patients and healthy controls, belonging to 9 subclasses (triglycerides, sphingomyelin, phosphatidylserine, phosphatidylethanolamine, monofatty acid glycerides, lysophosphatidylcholine, hexose ceramide, diglycerides, and cardiolipin). When the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, or those of phosphatidylserine (18.0_18.1) and H served as diagnostic markers separately, the areas under the ROC curve (AUCs) were all > 0.8, and the AUCs of 16 differential lipid molecules were all > 0.7. Conclusion:The serum lipid composition differed between healthy controls and CAD patients, and the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, and those of phosphatidylserine (18.0_18.1) and H may be promising biomarkers for the diagnosis of CAD.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Objective:To investigate the related genes, signaling pathways and possible mechanisms of malignant transformation of human papillomavirus type 16 (HPV-16) immortalized cervical epithelial cell line H8.Methods:The malignant transformed H8 cell model was constructed, and the changes of cell invasion ability and cell migration ability of H8 cells after malignant transformation were detected by Transwell assay, and the changes of clone formation ability of H8 cells after malignant transformation were detected by plate clone formation assay. Total RNA was extracted from malignant transformed H8 cells and H8 cells, and the two groups of cells were sequenced by transcriptome using Illumina novaseq 6000 sequencing platform, differentially expressed genes (DEGs) were identified and analyzed, and Gene Ontology (GO) function enrichment analysis, Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and protein-protein interaction were performed.Results:The invasion ability, migration ability and clone formation ability of malignant transformed H8 cells significantly increased as compared to H8 cells. A total of 203 differentially expressed genes were identified in H8 cells before and after malignant transformation, of which 98 were up-regulated and 105 down-regulated. GO enrichment analysis showed that DEGs were mainly involved in biological processes such as cellular processes, biological regulation, and metabolic processes. KEGG pathway enrichment analysis showed that DEGs were mainly enriched in alanine, aspartate and glutamate metabolic pathway, glycine, serine and threonine metabolism pathway, p53 signaling pathway and TGF-β signaling pathway, PI3K-Akt signaling pathway. PPI analysis screened 10 hub genes including DDIT3, TRIB3 and ASNS.Conclusions:Compared with H8 cells, malignant transformed H8 cells have a large number of differentially expressed genes and pathways at the transcriptional level, which could further provide new ideas for the mechanism of malignant transformation and carcinogenesis as well as finding new targets for the prevention of malignant transformation.