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

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective:To express prokaryotically GII.4 human norovirus (HuNoV) VP2 protein and to prepare polyclonal antibody against VP2.Methods:Design specific primers to amplify the VP2 gene of GII.4 HuNoV, digest and connect to the prokaryotic expression vector pGEX-6P-1, transform the correctly identified recombinant plasmid into BL21 ( DE3) competent cells.Pick out and shake the monoclonal bacteria, and add IPTG to induce recombinant GST-VP2. The fusion protein was expressed, purified by GST affinity chromatography and digested to obtain GII.4 HuNoV VP2 protein. The relative molecular mass (Mr.×10 3) of the purified HuNoV VP2 protein was analyzed by SDS-PAGE. BALB/c mice were immunized with purified GII.4 HuNoV VP2 protein (0.5 mg/ml) to prepare polyclonal antibodies. Results:The VP2 protein of GII.4 HuNoV was successfully expressed and purified, with a relative molecular mass (Mr.×10 3) of about 29; the VP2 polyclonal antibody of GII.4 HuNoV was successfully prepared and its titer was as high as 1∶1 280 000. Western blot and indirect ELISA analysis showed that the polyclonal antibody could specifically bind to the VP2 antigen of GII.4 HuNoV. Conclusions:The purified GII.4 HuNoV VP2 after prokaryotic fusion expression can be used to prepare high titer polyclonal antibody.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

Objective To investigate the effects of leuprolide acetate microspheres (Evan Bayh) in the treatment of adenomyosis with infertility by IVF-ET.Methods From January 2012 to May 2016 ,122 cases of adenomyosis combined with infertility were selected in the reproductive medicine center of the hospital as the research subjects ,all the patients were randomly divided into experimental group and control group with 61 patients in each group according to the order of admission ,the experimental group was received injection of Evan Bayh ,the control group was given injection of triptorelin acetate treatment ,and then all patients were given the in IVF-ET treatment ,investigation and prognosis.Results The dosage of gonadotropins(Gn) in the experimental group was less than that in the control group ,and the use time of Gn was lower than that of the control group ,and the differences between the two groups were statistically significant (P＜0.05).The lutein-izing hormone(LH) in the experimental group was significantly higher than that in the control group at the human chorionic gonadotropin(HCG) injection time ,while the estradiol(E2) ,progesterone(P) and endometri-um thickness were significantly lower than those of the control group (P＜ 0.05).The number of retrieved eggs and the number of transplantable embryos in experimental group were lower than those in control group (P＜0.05) ,the rate of cycle cancellation was higher than that of control group (P＜0.05) ,and there was no significant difference in clinical pregnancy rate compared between the two groups (P＞0.05).Conclusion The application of Evan Bayh in adenomyosis combined with infertility patients in the treatment of IVF-ET can re-duce the dose of Gn and the use of time ,promote normal hormone secretion ,improve the patient's oocyte num-ber ,the number of embryos ,reduce the cycle cancellation rate ,and has good application value.

Objective To establish a SYBR Green real-time PCR detection method with tissue-specific miRNAs and explore a novel approach for forensic body fluid identification. Methods The frequently reported 6 standard miRNAs were synthesized to establish a SYBR Green method, and verify with body fluid. The relative expression data for the 6 miRNAs were obtained using SYBR Green real-time PCR method in peripheral blood, menstrual blood, saliva and semen. Results The assays showed that miRNA205 permitted the unequivocal identification among different fluids. miRNA451 and miRNA144 could be used to distinguish blood from non-blood. Menstrual blood or peripheral blood could be identified through miRNA214. miRNA888 and miRNA891 was highly expressed in semen. Conclusion The results of this study indicate that miRNA SYBR Green profiling may provide a feasible and effective approach to body fluid identification for forensic casework.

Objective To explore the role of beta-2 adrenergic receptor in the pathogenesis of infantile hemangioma.Methods In vitro cultured infantile hemangioma endothelial cells were divided into propranolol and isoproterenol groups.The propranolol groups were further classified into 5 groups to be treated with propranolol solutions at concentrations of 10,15,20 μg/ml,EGM-2 medium (blank control group 1),and EGM-2 medium containing 0.16％ DMSO (DMSO group) respectively,while the isoproterenol groups were classified into 4 groups to be treated with isoproterenol solutions at concentrations of 5,10,20 μg/ml and EGM-2 medium (blank control group 2) respectively.After 24-and 48-hour treatment,enzyme-linked immunosorbent assay (ELISA) was performed to measure the expression of beta-2 adrenergic receptor in cell culture supernatants in the above groups.Results After 24-hour treatment,15-μg/ml and 20-μg/ml propranolol groups showed significantly decreased expression of beta-2 adrenergic receptor compared with blank control group 1 and DMSO group (all P ＜ 0.05).After 48-hour treatment,all the propranolol groups showed significantly decreased expression of beta-2 adrenergic receptor compared with the blank control group 1 (all P ＜ 0.05).However,the expression of beta-2 adrenergic receptor was significantly higher in the 10-and 20-μg/ml isoproterenol groups than in the blank control group 2 after 24-hour treatment (all P ＜ 0.05),and higher in the 20-μg/ml isoproterenol group than in the blank control group 2 after 48-hour treatment (P ＜ 0.05).Conclusion Propranolol can down-regulate the expression of beta-2 adrenergic receptor on the surface of vascular endothelial cells,while isoproterenol can up-regulate its expression.

Objective To explore the pathological features of Aβ1-42 deposition and its correlation with Apolipoprotein E in brain of streptozotocin (STZ)-induced type Ⅱ diabetic rats.Methods High fat diet combined with small dose of STZ induced diabetic rats were adopted as experiment rats,and randomly divided into 3 months old diabetes mellitus group and 6 months old diabetes mellitus group (n=15).Healthy Wistar rats were adopted as control rats,and divided 3 months old control group and 6 months old control group (n=15).The Aβ1-42 and ApoE location and expressions were detected by immtmohistochemistry.Real-time fluorogenic quantitative-PCR and Westem blotting were used to detect the mRNA and protein levels of ApoE in each group.Results Immunohistochemical results showed that Aβ1-42 in the brain of the diabetic rats gathered around the vessel wall and blood vessel.The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group as compared with those in the 3 months old diabetes mellitus group (P＜0.05).The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old control groupas compared with those in the 3 months old control group (P＜0.05).As compared with that in the 6 months old control group,the number of Aβ11-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group (P＜0.05).As compared with that in the 3 months old control group,the number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions was significantly increased in the 3 months old diabetes mellitus group (P＜0.05).Person correlation coefficient indicated that the number of positively-stained cells of Aβ-42 was positively correlated to ApoE protein expression level (r=0.9755,P=0.000).Conclusions Aβ1-42 in the brain of type Ⅱ diabetic rats expresses both in blood vessel wall and around blood vessel.Age and duration of diabetes can increase the deposition of A3 and ApoE in brain tissues,and there is a positive correlation between them.

Objective To explore the influence of structured lipid emulsion on acute phase protein and acute inflammatory reaction in gastrointestinal cancer patients after operation.Methods Eighty postoperative patients with gastrointestinal caner from July 2010 to February 2012 were randomly divided into observation group and control group,and 40 cases for each group.Patients in observation group were given structured lipid emulsion,while in control group were given physic mixture of medium-chain/long-chain triglycerides group.Meanwhile patients in both groups were received isonitrogenous and isocaloric parenteral nutrition for 6 days after operation.The general conditions after operation were recorded.Acute phase protein and acute inflammatory reaction were measured before operation,the 1 st day and 7th day after operation.Results After 6 days parenteral nutrition,the vital sign data,blood routine indices,liver and renal function,blood fat were back to normal values in two groups.There was no significant difference in the incidence of postoperative infection complication and hospitalization duration between observation group and control group (12.5％ (5/40) vs.25.0％ (10/40) ; (12.9 ± 0.7) d vs.(13.1 ± 0.9) d; P ＞ 0.05).The serum levels of Albumin (ALB),Prealbumin(PAB) and Transferrin(TRF) on the 1st day after operation in two groups were significantly lower than those before operation,while the serum levels of C reactive protein (CRP) and fibrinogen (Fib) were significantly higher,then gradually recovering.The serum levels of ALB,PAB,TRF,CRP,Fib on the 7th day after operation in observation group were (37.11 ± 3.30) g/L,(0.25 ± 0.08) g/L,(2.35 ± 0.49) g/L,(21.84±16.76) mg/L,(3.95 ± 1.23) g/L,significant different from those on the 1st day before nutrition therapy ((31.52±2.92) g/L,(0.15 ±0.02) g/L,(1.90 ±0.54) g/L,(83.80 ±47.13) mg/L,(4.35 ±0.98) g/L) and control group ((34.50 ±2.71) g/L,(0.18 ±0.05) g/L,(2.00 ±0.52) g/L,(41.36 ±23.49) mg/L,(4.76 ± 2.35) g/L; P ＜ 0.05).The serum levels of interleukin (IL)-1,IL-2,IL-6,tumor necrosis factor (TNF)-α decreased on the 1st day after operation of two groups,then gradually increasing.The serum levels of IL-2,IL-6 on the 7th day after operation in observation group were (987 ±203) ng/L) and (277 ± 107) ng/L,significant different from those on the 1st day before nutrition therapy ((890 ± 197) ng/L and (355 ± 107) ng/L;P ＜0.05),and lower than those in control group ((1 347 ± 195) ng/L,(752 ± 187) ng/L; P ＜0.05).The serum levels of TNF-α on the 7th day after operation in observation group was (197 ±98) ng/L,which was as same as that on the 1 st day before nutrition therapy ((167 ± 79) ng/L,P ＞ 0.05) and lower than this in control group((342 ± 106) ng/L;P ＜0.05).Conclusion Structured lipid emulsion can effectively improve the synthesis of acute phase protein in gastrointestinal cancer patients after operation,regulate the inflammatory cell factors producing and releasing,which is benefit to smoothly through stress reaction period.