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

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male

Objective To explore the morphological symmetry of the anterior circulation cerebral arteries based on digital subtraction angiography(DSA),and to analyze the value of arterial walking route on the healthy side in guiding catheterization in endovascular treatment for patients with sick-side major artery occlusion of the anterior circulation.Methods A total of 250 consecutive patients who underwent cerebral angiography at the Shengli Oilfield Central Hospital of China between January 2021 and August 2022 were enrolled in this study as angiography group,which was subdivided into youth angiography subgroup(＜50 years),middle-aged angiography subgroup(50-69 years),and elderly angiography subgroup(≥70 years).Other 170 patients with acute occlusion of the anterior circulation vessels,who received emergency mechanical thrombectomy,were collected as thrombectomy group.After successful recanalization,the cerebral angiographic imaging findings of both groups,including the arterial walking route symmetry of bilateral C1 segment,C2-C3 segment,ophthalmic segment,M1 segment proximal to the bifurcation,and M1 segment distal to the bifurcation,were analyzed and compared between the two groups.The recanalization rate and the consistency of bilateral arterial walking route in the thrombectomy group were also analyzed.Results No statistically significant differences in the arterial walking route of the C1 segment,C2-C3 segment,ophthalmic segment,M1 segment proximal to the bifurcation,and M1 segment distal to the bifurcation existed between the left side and right side(all P＞0.05).Ordinary bilateral symmetry was observed in M1 segment proximal to the bifurcation,and excellent bilateral symmetry was observed in all the other segments.There were no statistically significant differences in the bilateral arterial walking route of the C1 segment,C2-C3 segment,ophthalmic segment,M1 segment proximal to the bifurcation,and M1 segment distal to the bifurcation between each other among the three subgroups(all P＞0.05).Ordinary bilateral symmetry of the C1 segment was observed in the youth angiography subgroup,ordinary bilateral symmetry of the M1 segment proximal to the bifurcation was observed in all three subgroups,and excellent bilateral symmetry was observed in all the other segments.In the thrombectomy group the recanalization rate was 95.5％and the consistency rate of bilateral arterial walking route was 89.0％.Conclusion Bilateral symmetry exists in the C1 segment,C2-C3 segment,ophthalmic segment,M1 segment proximal to the bifurcation,and M1 segment distal to the bifurcation of the anterior circulation cerebral arteries.These findings provide a reliable basis of referring healthy-side arterial walking route to guide catheterization in endovascular treatment for mechanical thrombectomy and recanalization of sick-side major artery occlusion of the anterior circulation.(J Intervent Radiol,2024,33:472-478)

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective To evaluate the effect of head-mounted virtual reality display on the visual function of adult myopia.Methods Thirty-four myopia patients were divided into two groups by random number table method:test group(n=18)and control group(n=16).After routine eye examination of the subjects,the naked vision,corrected vision,dynamic stereopsis,near stereopsis,contrast sensitivity,assemble value,disperse value,positive relative accommodation(PRA),negative relative accommodation(NRA),flexibility of accommodation,and amplitude of accommodation(AMP)before the test,after the test 1 time and after the test 10 times;the visual fatigue questionnaire score and the visual work ability answer score were performed before the test and after the test 10 times.Results There was significantly statistically significant of naked eye vision in test group after the test 10 times compared with the pre-test and the control group(P were 0.040,0.011);There was significantly statistically significant in assemble value of the test group after the test 10 times compared with the pre-test and the control group(P were 0.036,0.010);there were significantly statistically signifi-cant in the NRA and adjustment flexibility of the test group compared with the pre-test and the control after after the test 10 times(P were＜0.0001,＜0.0001,0.008,0.017);there were not statistical differences in corrected visual acuity,contrast sensitivity,spread value,dynamic stereopsis,near stereopsis,PRA,AMP,visual fatigue questionnaire scores and visual work ability were not statistically significant in comparison between the control group and the test group on the corresponding time points(P＞0.05).Conclusion This is helpful to improve some of the visual function parameters of myopia patients appropriate using of head-mounted virtual reality technology training such as naked vision,NRA,insufficient collection,and flexibility of adjustment.

Objective Utilizing a specially engineered miR-144-GFP-H1 human embryonic stem cell(hESC)reporter line,this study leverages GFP fluorescence as an indicator of miR-144 expression to gauge the progression of erythropoiesis.The investigation is aimed at elucidating the potential roles of lncRNAs within the erythropoietic framework and conducting an initial assessment of their functional impact.Methods The miR-144/451-GFP-H1 cell line(hereafter referred to as 144-H1)was utilized for in vitro erythrocyte induction culture.The subpopulations of cells entering the erythropoiesis stage were characterized by the surface molecules CD71 and GPA.The GFP reporter gene of miR-144 served as a critical determi-nant to distinguish between GFP-positive cells(with a high propensity for erythropoiesis)and GFP-negative cells(with a low propensity for erythropoiesis).Transcriptome sequencing was performed on both groups to identify differentially ex-pressed long non-coding RNAs(lncRNAs).LncRNA entries with potential for validation were selected for preliminary func-tional verification.The CRISPR/Cas9 gene editing technique was employed to design functional interference strategies for the targeted lncRNAs,obtaining 144-H1 cell lines with knocked-out function of the specific lncRNAs.These knockout cell lines,along with non-knockout 144-H1 cell lines,were used for parallel erythrocyte induction culture to identify differential nodes.This approach preliminarily verified their impact on erythropoiesis in an in vitro development model.Results 1)The constructed 144-H1 cell line was capable of expressing GFP fluorescence upon entering the stage of in vitro erythrocyte in-duction,indicating the activation of miR-144/451.2)Within the CD71,GPA double-positive group,significant differences in lncRNA expression were observed between the GFP-positive and GFP-negative subpopulations.3)Gene editing strategies involving the deletion of sequence segments capable of effectively interfering with the function of multiple lncRNA entries were designed and verified for successful editing.In the knockout cell lines,parts of the lncRNA sequences were directly de-leted.4)In parallel validation experiments of erythrocyte induction culture,cell lines with LINC01569 knocked out exhibited significant differences in flow cytometric subpopulations and cell proliferation capabilities compared to the non-knockout cell lines:①The knockout cell lines showed sustained high expression of GFP fluorescence.②The proportion of the CD71-GPA double-positive group in the knockout cell lines continuously decreased during erythrocyte maturation.③No significant ex-pression of hemoglobin was observed in the knockout cell lines,lacking the characteristic red color.④The cell proliferation capability of the knockout cell lines was significantly lower than that of the non-knockout cell lines(P＜0.05).Conclusion The successful employment of the 144-H1 cell line facilitated an exploration into the potential functions of lncRNAs in e-rythropoiesis.This enables the design of more refined in vitro developmental experiments to enhance the precision in captu-ring lncRNA functions.Among the differentially expressed lncRNA entries,LINC01569 was preliminarily validated to play a regulatory role in erythropoiesis.The functional absence of LINC01569 severely impacts the normal differentiation and prolif-eration of erythrocytes.The specific regulatory mechanism of LINC01569 in erythropoiesis warrants further investigation and research.

Objective To explore the mechanism of lupinol on the proliferation,apoptosis,migration and invasion of lung cancer cells through regulating Notch signaling pathway.Methods Lung cancer cells A549 were cultured in vitro,and the cells were treated with lupeol at concentrations of 0,15,30,and 60 mg/L,with 0 mg/L being the control group and the rese being the lupeol dosage groups,the cells were treated with lupinol at the concentration of 60 mg/L and Notch pathway inhibitor DAPT at the concentration of 10 μmol/L,which was recorded as the lupeol+DAPT group.Cell proliferation changes were detected by MTT;cell apoptosis was detected by flow cytometry;cell migration and invasion were detected by Transwell;protein expression of PCNA,Bcl-2,N-cadherin,E-cadherin,Notch-1 and Hes-1 were detected by Western blot.Results 15,30,60 mg/L lupeol group can significantly inhibit the cell viability,the number of migration cells and invading cells of lung cancer cells,significantly increase the rate of cell apoptosis,and reduce PCNA,N-cadherin,Bcl-2,Hes-1 and Notch-1 expression,increase E-cadherin expression(P＜0.05).Compared with the lupeol group,the lupeol+DAPT group significantly reduced cell viability,the number of migrating cells and invaded cells,increased apoptosis rate,decreased PCNA,Bcl-2,Hes-1,Notch-1 and N-cadherin protein expression,and increased E-cadherin protein expression(P＜0.05).Conclusion Lupinol may inhibit the invasion,migration and proliferation of lung cancer cells through Notch signaling pathway,and induce apoptosis.

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.