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 therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.

Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery, which has merits of biocompatibility, biodegradability and mild gelation conditions. However, its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity. Moreover, for the intracellularly acted proteins, cell membrane as a primary barrier hinders the transmembrane delivery of proteins. The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes. We herein develop a protease-manipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins. The embedded polymeric nanogels (CytoC/aNGs) preserve activity of cytochrome

Objective To investigate the bacteriostasis effect of combination of Shuanghuanglian powder with piperacillin/tazobactam or cefoperazone/sulbactam for extensively drug-resistant Acinetobacter bauman-nii in vitro.Methods The minimum inhibitory concentration(MIC)and partial inhibitory concentration(FIC) index of 30 clinical isolates of Acinetobacter baumannii were measured with different concentrations of Shuan-ghuanglian,piperacillin/tazobactam,cefoperazone/sulbactam or combination.The effect of combined medica-tion was determined by FIC index.Results After shuanghuanglian combined with piperacillin/tazobactam,no strain showd synergistic effect;16.7% of the strains showed additive effect;83.3% of the strains showed ir-relevant effect;no strain showed antagonistic effect.After Shuanghuanglian combined with cefoperazone/sul-bactam,23.3% of the strains showed synergistic effect;73.3% of the strains showed additive effect;3.3% of the strains showed irrelevant effect,no antagonistic effect was shown.Conclusion The antibacterial effects of Shuanghuanglian and piperacillin/tazobactam were mostly irrelevant,while the antibacterial effect of Shuang-huanglian and cefoperazone/sulbactam are mostly synergistic and additive effect,w hich had better antibacterial effect to Acinetobacter baumannii in vitro.

Objective To compare the test performance of different immunoassays for the detection on autoantibodies specific to primary biliary cholangitis,including anti-mitochondrial type 2 antibody(AMA-M2),anti-glycoprotein 210(anti-gp210)and anti-nuclear body protein sp100(anti-sp100).Methods Serum samples from Primary Biliary Cholangitis(PBC, n=91), liver disease control(including viral hepatitis,autoimmune hepatitis and liver cirrhosis,n=67)and healthy individual(n=40)were collected from Beijing Youan Hospital during the period between April 2014 and April 2017.All samples were tested with chemiluminescent immunoassay(CLIA)and enzyme linked immunosorbent assay(ELISA)for AMA-M2, meanwhile the detection on anti-gp210 and anti-sp100 were compared between CLIA and Line Immunoassay(LIA).The Kappa coefficient were used to measure the level of qualitative agreement between different assays.The diagnostic accuracy of AMA-M2 detected with CLIA and ELISA were compared by receiver operating characteristic curve(ROC).Results The overall qualitative agreement between CLIA and ELISA for the detection to AMA-M2 is 88.4%(Kappa =0.765, P<0.01).Excellent qualitative agreement between CLIA and LIA for the detection to anti-gp210 and anti-sp100 was also found with overall agreement as 96.5%(Kappa=0.852,P<0.01)and 98%(Kappa=0.884,P<0.01), respectively.The ROC analysis also showed similar area under the curve(AUC)for CLIA(0.965, P<0.01)and ELISA (0.928,P<0.01)on detection to AMA-M2.Conclusions CLIA and ELISA showed excellent agreement for the detection to AMA-M2.High qualitative agreement between CLIA and LIA was also found when testing anti-gp210 and anti-sp100.

Objective To produce the biological calcium citrate cement with fresh oyster shells, and investigate its compressive strength and biocompatibility so as to provide the experimental basis for clinical application of the material.Methods The compressive strength of biological calcium citrate cement was measured and its surface morphology was observed by SEM.The calcium release curve and pH value were measured in the simulated body fluid.Last, its biocompatibility was detected by cytotoxicity test.Results Biological calcium citrate cement produced by 0.33mL/g liquid solid ratio had the maximum compressive strength, and the crystal structure of the material was uniform and orderly.The determination of pH value showed that the degradation and absorption of biological calcium citrate cement did not significantly change the pH value of the body fluid.With gradual degradation of the material, the concentration of Ca2+ in the solution increased gradually.Cytotoxicity test showed that this material had good biocompatibility and no cytotoxicity.Conclusion Biological calcium citrate cement possesses strong compressive strength and good biocompatibility, and it can form a microenvironment with low in alkaline and high in calcium.

After a description of the demand for medical information in grass-root PLA health units, the experiences of Medical Library of Chinese PLA in providing medical information service for grass-root PLA health units were summarized, and suggestions were proposed for medical library and information institutions to provide information service for them.

OBJECTIVETo investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai, and to provide a scientific basis for developing prevention and treatment measures.

METHODSFrom April 2005 to September 2014, 5,146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study. Clinical data of the 4,660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN. The incidence rate of cholestasis was assessed for relation to age, sex, etiology, and type of liver disease, and statistically compared to the general clinical data and specific biochemical indicators with potential sex-related differences. T-test and chi-square test were performed for the statistical analyses.

RESULTSOf the 4,660 study participants, 10.26% had cholestasis; the prevalence of cholestasis increased with increasing age in male patients. The distribution of the cholestasis incidence according to the type of chronic liver disease was: 75.00%, primary sclerosing cholangitis; 42.86%, primary biliary cirrhosis; 35.97%, hepatic tumor; 30.77%, autoimmune hepatitis; 28.31%, drug-induced liver disease; 16.46%, alcoholic hepatitis; 13.98%, cryptogenic cirrhosis; 12.99%, schistosomal cirrhosis; 7.53%, alcoholic cirrhosis; 7.32%, mixed cirrhosis; 5.94%, viral liver cirrhosis; 2.70%, nonalcoholic fatty liver disease. There was no significant difference in the prevalence of cholestasis between the two sexes. In the patients with cholestasis, the levels of GGT and total bilirubin were significantly different between the two sexes.

CONCLUSIONThe incidence rate of cholestasis in first-hospitalized patients with chronic liver disease was 10.26%, and the rate increased with increased age. Patients with primary sclerosing cholangitis or primary biliary cirrhosis had higher incidence rates of cholestasis. Incidence rates of cholestasis of the various chronic liver diseases were not related to sex.

Bilirubin ; China ; Cholestasis ; Chronic Disease ; Humans ; Incidence ; Liver Diseases ; Male ; Prevalence ; Retrospective Studies ; gamma-Glutamyltransferase

Humans ; Hydroxycholecalciferols ; blood ; Pneumoconiosis ; blood