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

As a famous acupuncturist in the world, professorbelieves the key of acupuncture technique is the use of force, and the understanding of the "concentrating the force into needle body" is essential to understand the essence of acupuncture technique. With deep study of Huangdi Neijing () and(), the author further learned professor's theory and operation specification of "concentrating force into needle body, so the force arriving before and together with needle". The whole-body force should be subtly focused on the tip of needle, and gentle force at tip of needle could get significant reinforcing and reducing effect. In addition, proper timing at tip of needle could start reinforcing and reducing effect, leadto disease location, and achieve superior clinical efficacy.

OBJECTIVETo investigate the differential gene expression profile of the lung tissues in experimental silicosis rats and to screen for and identify the key signal transduction pathways in pulmonary silicotic fibrosis.

METHODSA total of 80 rats were randomly divided into control group (n = 40) and silica-instilled group (n = 40). Each group was equally divided into five subgroups, and each subgroup was treated at 1, 7, 14, 21, or 28 d. Intratracheal instillation was used to give 1 ml of silica suspension (50 mg/ml) in the silica-instilled group and normal saline in the control group. Silicotic nodules and type I and III collagen were observed through hematoxylin and eosin staining and Sirius red staining, respectively. Differentially expressed genes in pulmonary silicotic fibrosis were selected by the rat whole-genome gene expression RatRef-12 BeadChip (Illumina, USA), and a fold change cutoff was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) was also used to verify differentially expressed genes. Through bioinformatics databases such as Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG), preliminary research was performed on the biological pathways of differential genes, key biological signal transduction pathways were identified, and key differentially expressed genes in each pathway at different time points were searched for.

RESULTSA total of 2694 genes were differentially expressed and changed dynamically. The KEGG pathway analysis showed that 141 signal transduction pathways were involved in the development and progression of pulmonary silicotic fibrosis, among which 48 pathways were more significant than others (P < 0.01), with the mitogen-activated protein kinase (MAPK) pathway exceptionally significant. The differentially expressed genes interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and transforming growth factor beta (TGF-β) in the MAPK pathway were up-regulated at different time points after silica instillation. The results of real-time PCR showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was over-expressed at 4 time points and under-expressed at 1 time point compared with the control group.

CONCLUSIONThe MAPK signal transduction pathway plays a very important role in the development of pulmonary silicotic fibrosis. Both IL-1R and TNFR may play major roles during inflammation phase through the P38/Jun N-terminal kinase (JNK) pathway, and TGF-β may have important function through the extracellular-signal-regulated kinase (ERK) pathway in the formation of fibrosis.

Animals ; Gene Expression ; Lung ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; genetics ; metabolism ; pathology ; Rats ; Rats, Wistar ; Signal Transduction ; Silicosis ; genetics ; metabolism ; pathology

Objective To induce and identify the differentiation of rat bone marrow mesenchymal stem cells(MSCs)into cardiomyocytes in vitro,and observe the expression of Nesprin protein during the differentiation. Methods Rat MSCs were isolated and purified by Ficoll density gradient centrifugation,and adhered for serial subcultivation.Surface-associated antigens of MSCs of the second passage were dedected by flow cytometry.MSCs of the second passage were induced by 10μmol/L 5-azacytidine(5-Aza)to differentiate into cardiomyocytes,and the morphological changes were observed.The expression of Desmin,α-sarcomeric actin and cardiac Troponin I(cTnI) mRNA and protein was detected by RT-PCR,immunocytochemistIv and immunofluorescence staining, and the expression of Nesprin protein was detected by Western blotting. Results The morphology of MSCs induced by 5-Aza was bigger and longer,and the nuclei became bigger,exhibiting more consistent patterns.The expression of Desmin,α-sarcomeric actin and cTnI mRNA and protein of MSCs was positive.Immunofluorescence staining revealed that Nesprin protein positioned in the nuclear membrane,and Western blotting detection demonstrated that the expression of Nesprin protein significantly increased after differentiation(P<0.05).Conclusion MSCs may be successfully induced to differentiate into cardiomyocytes.The expression of Nesprin protein in the differentiated MSCs may significantly increase,indicating Nesprin may play a role in the differentiation from MSCs to cardiomyocytes.

objective To explore the indication of mechanical ventilation and evaluate the effects of mechanical ventilation with the least delay on the Severe cases of hand-foot-mouth disease(HFMD).Methods Retrospective cohort study was conducted among the severe HFMD cases(n=66)admitted to pediatric intensive care unit(PICU)between July 2008 and september 2009.Sixty-six cases were divided into two groups:42 cases(group A,July 5 to October 31,2008)were ventilated with the common mechanical ventilation,24 cases(group B,April 21 to september 30,2009)were ventilated at least delay when the symptoms of neurogenic pulmonary edema appeared.Then the diffcrences on the survival rate and the mortality in the group A and group B were investigated.Results Twenty out of 42 patients died(47.6%),eighteen were cured(42.6%) and four showed improved signs(9.5%)in group A.Twenty-two out of 24 patients were cured(91.7%),two showed improved signs(8.3%)and no death in group B.The clinical effect of group B was much better tllan group A(P<0.001).Conclusion Early mechanical ventilation would improve the survival rate and decrease the mortality of severe hand-foot-mouth disease.

Objective To study the effect of different approach on myocardial contractile force, angiogenesis and collagen renovation in acute myocardial infarct site by implantation of bone marrow mesenchymal stem cells (MSCs). Methods 32 Gui-zbou Xiang porcine were randomly divided into control group (group C), intra-coronary arterial injection group (group A) ,topical injection group (group T) and intra-coronary arterial + topical injection group( group A + T). 3 ml bone marrow was extracted. MSCs were cultured according to the methods of Wakitani's. After being co-cultured with 5-azacytidine for 24 hours, these cells were labelled with bromodeoxyuridine ( BrdU ). Autologus MSCs were implanted into the acute myocardial infarct site via the distal segment of the ligated left anterior descending artery (LAD) ,topical injection and both. Specimens and muscle strip were harvested in 3 and 6 weeks after MSCs implantation for microvessel count, P Ⅲ NP activity and contractile force measurement. Results The contractile force(48.6±5.9) %, (42.1±6.2 ) %, ( 56.9±5.1 ) %, microvessel count ( 19.6±4.3,17.1±4.0, 23.2±5.5 ) and collagen renovation (4.6±0.5 ) μg/L, ( 5.9±0.7 ) μg/L, ( 3.9±0.3 ) μg/L in the cell implant groups was better than that in the control group(37.9±5.4)% ,13.2±3.8,(8.7±0.8) μg/L,(P <0.01) ,espe-cially in group A + T. Conclusions Implantation of MSCs through intra-coronary arterial plus topical injection of MSCs maybe an ideal approach for infracted myocardium.

Objective To retrospectively analyse the clinical data of off-pump coronary artery bypass grafting surgery(OPCAB)in our department and summarize the clinical experience of peri-operative management.Methods From January 2007 to May 2008,253 patients underwent OPCAB.Seventy-six cases with left main disease(including 18 cases of single left main lesion and 58 cases of complex lesion);13 cases had single vessel disease;32 cases had double vessels disease and 190 cases had triple vessels disease.Eighteen cases received emergency OPCAB.All vessel anastomosis were performed with coronary artery stablizer and shunt through median sternotomy.Resuits Three cases died after operation(1.2%).Intra-aortic balloon pump was used in 11 cases.Mechanical ventilation time was 3-168 h[(24.1±22.3)h],and ICU stay time was 1-14 day[(2.8±2.0)d].Postoperative hospital stay time was 8-42 days[(15.6±6.3)d].Conclusion OPCAB is reliable for most bypass cases.With appropilate peri-operative management,a satisfied result will be acceptable.

Objective To summarize the clinical experiences of 1386 patients undergoing off-pump coronary artery bypass grafting(OPCAB)during Jan 2002 to Mar 2008.Methods OPCAB was done through midsternumtomy under ordinary-temperature anesthesia after radial artery,left breast artery and vena saphena magna were taken.Patients over 70 years old accounted for 32.35%,and the oldest was 99 years old.Emergency and subemergency OPCAB was done in 111 cases,re-do CABG with off-pump technique was done in 52 patients.Results 24 cases died during perioperation,with mortality of 1.73%and all other patients discharged from the hospital.Following operation,the symptoms of angina pectoris were relieved and the life quality was much beaer than that before operation.Conclusion OPCAB is feasible for older patients,who are complicated with other chronic diseases for elder patients.Skillful technique of surgeon,right indications for OPCAB and management of peri-and postoperation are key to success of operation.

Objective To summarize the clinical experiences and early-to median effect of coronary artery bypass grafting(CABG)in patients aged 70 years or above.Methods From Dec.2006 to Dec.2007,86 patients aged 70 or above underwent CABG,of whom 71 cases underwent off-pump coronary artery bypass grafting(OPCAB),15 cases had CABG with cardiopulmonary bypass(CPB).5 cases underwent mitral valve replacement,3 underwent aortic valve replacement besides CABG,and one case underwent removal of ventricular aneurysm.Their clinical data were retrospectively analyzed.Results There was one case who died of enterobrosis after operation.The average ICU stay time was(77.4±49.6)h,the average postoperative stay time was 15 d,and the average drainage was 530 ml.22 postoperative complications were found.76 cases were followed up for 10-22 months.Follow up effect was better showing cardiac classification I-II and no angina pectoris,myocardial infarction and late death.Conclusion Patients with coronary heart disease in good condition will have not remarkable improvement in mortality as compared with ordinary patients but attention should be paid to their preoperative pulmonary function and angina pectoffs.OPCABG would have encouraging result in reducing the rate of postoperative complications and hospital death,which should be recommended as the first choice for the elderly patients.