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

Objective This paper aims to explore patient satisfaction with mobile medical payments in ethnic minority areas and its influencing factors.Methods From May to August 2023,565 ethnic minority patients from 6 villages in 4 ethnic minority autonomous counties in Dehong Prefecture and Pu'er City,Yunnan Province,were selected as research subjects,and 186 Han patients in Kunming were selected as controls.The general information questionnaire,the mobile medical payment will-ingness and attitude survey scale,and the medical cost mobile payment satisfaction survey scale were used to investigate their sat-isfaction with actual situation of medical mobile payment.Additionally,this paper discussed influencing factors affecting satisfac-tion.Results The ethnic minority patients exhibited a significantly lower level of satisfaction compared to the Han patients(39.65±10.43 vs.49.54±7.88,P＜0.05).ethnic minority patients scored significantly lower on the dimensions of satisfac-tion,such as perceived safety,ease of use and usefulness of mobile medical payment compared to the group of Han patients(all P＜0.05).Additionally,they ethnic minority patients showed significantly lower level of willingness and attitude to use mobile medical payment compared to the group of Han patients(P＜0.05).The main factors influencing the significant difference in satisfaction with mobile medical payment were ethnic group,number of hospital visits in previous year,first-time use of mobile medical payment,and educational background(P＜0.05).Conclusion Ethnic minority patients have a low perception of secur-ity,ease of use,and usefulness of mobile medical payments,as well as a low willingness and characteristics for mobile medical payment.Therefore it is necessary to further enhance their experience and satisfaction.In the development of mobile medical pay-ment services hospitals should fully consider the current situation of"illiteracy""semi-illiteracy"and"lack of resources"in re-mote ethnic areas.They should actively develop service platforms and applications suitable for mobile medical payment in ethnic minority areas to continuously enhance service efficiency and quality.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR. METHODS: IUGR models were established in Sprague-Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1-4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1-4 binding sites were studied by pyrosequencing. RESULTS: The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1-4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05). CONCLUSION The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Objective:To investigate the clinical effect of Ilizarov technique with compression and distraction osteogenesis in treatment of traumatic femoral shaft defects.Methods:A retrospective case series study was conducted to analyze the clinical data of 52 patients with traumatic femoral shaft defects admitted to West China Hospital of Sichuan University from September 2015 to September 2019，including 32 males and 20 females at age of 19-60 years［（40.3 ± 12.1）years］. There were 15 patients with fractures at the proximal 1/3，20 at middle 1/3 and 17 at distal 1/3 part of femoral shaft. Types of bone defects were bone defect after open fracture in 2 patients，infectious nonunion in 29 and atrophic nonunion in 21. Length of bone defects after debridement and osteotomy was 3.0-5.8 cm［（4.2 ± 0.8）cm］. A total of 24 patients underwent primary direct shortening and compression as well as re-lengthening of the broken ends；28 patients were operated by osteotomy and compression，and then by re-lengthening of the broken ends at Ⅱ stage with the average interval of 2.8 months. Postoperative wound healing，bone healing time，external fixation index（EFI）and complications were observed. Preoperative and postoperative levels of white blood cell count（WBC），C-reactive protein（CRP）and erythrocyte sedimentation rate（ESR）were measured. Association for the study and application of the method of Ilizarov（ASAMI）score was used to evaluate bone healing and functional recovery at the latest follow-up.Results:All patients were followed up for 20-60 months［（36.5 ± 10.3）months］. All wounds were healed at Ⅰ stage，with no infection or sinus tract recurrence. Bone healing time was 9-20 months［（14.5 ± 3.8）months］，and EFI was 1.2-1.9 months/cm［（1.5 ± 0.2）months/cm］. Nail tract infection was found in 14 patients，with the infection rate of 27%. Poor healing of broken ends fracture occurred in 4 patients，out of which 3 with infectious nonunion and 1 with atrophic nonunion. Axial deviation was observed in 2 patients and poor mineralization was observed in 1 patient. In 2 patients，the affected side was shortened by 1.8 cm and 2.0 cm when compared to the healthy side. At the latest follow-up，levels of WBC［（6.0 ± 1.4）× 10 9/L］，CRP［（6.8 ±1.7）mg/L］and ESR［（10.5 ± 6.1）mm/h］were lower than those before surgery［（9.2 ± 2.2）× 10 9/L，（31.7 ± 22.1）mg/L，（45.8 ± 31.3）mm/h］（ P < 0.01）. At the latest follow-up，bone healing rated on ASAMI score was excellent in 31 patients，good in 13 and fair in 8，with the excellent and good rate of 85%；limb function rated on ASAMI score was excellent in 28 patients，good in 14，fair in and good in 3，with the excellent and good rate of 81%. Conclusions:For traumatic femoral shaft defects，Ilizarov technique with compression and distraction osteogenesis can fully remove infection or ischemic bone lesions. Distraction osteogenesis technology can complete continuous compression of broken ends to further promote healing of broken ends and limb lengthening and attain limb reconstruction and bone healing and functional recovery.

Objective This study was to evaluate the safety of 640 corneal donors by analysing the serological testing results.Methods We retrospectively analyzed the serological testing results from Changsha Aier Eye Bank and Chengdu Kangqiao Aier Eye Bank from January 2011 to December 2015,hepatitis B virus surface antigen (HBsAg),hepatitis C virus (HCV),treponema pallidum (TP) and human immunodeficiency virus (HIV) were detected by colloidal gold or enzyme-linked immunosorbent assay (ELISA).Results There were 83 out of 640 serum samples showed positive immuno-reaction assayed markers,the positive rate was 12.97％,including HBsAg(n=60,9.38％),HCV(n=3,0.47％),TP(n=11,1.72％) and HIV(n=2,0.31％).Moreover,3 corneal donors were both positive against HBsAg and HCV,2 donors positive against HCV and TP,1 donor positive against HBsAg and HIV,1 donor positive against HBsAg and TP.Conclusions There is a high proportion of positive results of blood-borne diseases in cornea donors,which is a potential threat to corneal receptors and eye bank workers.Therefore,it is very important to detect serological test strictly for corneal donors.

Objective:To compare the proliferation and osteoblastic differentiation of dental pulp stem cell (DPSC)isolated from normal and inflamed pulps of different degrees in Beagle immature premolars, and provide evidence for the use of inflammatory DPSC (IDPSC).Methods:This study evaluated 14 Beagle’s young premolars (21 roots).In the experiment group,irreversible pulpitis was induced by pulp exposure and the inflamed pulps were extracted 2 weeks and 6 weeks after the pulp chamber opening.For the control group,normal pulps were extracted immediately after the exposure.HE staining and real-time PCR were performed to confirm the inflammation.The cells were isolated from the inflamed and normal pulps (IDPSC and DPSC).Cell proliferation and osteoblastic differentiation potentials of the two cells were compared.Results:Inflammation cells infiltration was observed in the inflamed pulps by HE stai-ning.The expression of inflammatory factor was much higher in the 6 week inflamed pulp.IDPSC had higher potential of cell proliferation and osteoblastic differentiation potentials.Furthermore,the osteoblas-tic differentiation potentials of IDPSC from 2 week inflamed pulp were higher than those from 6 week in-flamed pulp.Conclusion:The potential of cell proliferation and osteoblastic differentiation of DPSC was enhanced at early stage of irreversible pulpitis,and reduced at late stage in Beagle immature premolars.

Objective:To compare the effects of stromal cell-derived factor-1 (SDF-1 )and granulocyte colony-stimulating factor (G-CSF)on proliferation,migration,and odontoblastic differentiation of human dental pulp stem cell (DPSC)in vitro.Methods:DPSCs were cultured in vitro and treated with either 1 00 μg/L SDF-1 or 1 00 μg/L G-CSF.Cell counting kit-8 (CCK-8 )and colony-forming unit (CFU ) were used to detect the effect of SDF-1 and G-CSF on the proliferation ability of DPSC.Cell migration of DPSC was determined by wound healing assay and Transwell migration assay.The effects of SDF-1 and G-CSF on odontoblastic differentiation of DPSC were evaluated by alkaline phosphatase (ALP)staining, ALP activity and alizarin red S staining.The expression of odontoblastic-related genes such as dentin ma-trix protein 1 (DMP-1 )and dentin sialophosphoprotein (DSPP)were quantified by real-time RT-PCR. Results:SDF-1 and G-CSF promoted the proliferation of DPSC slightly,but the difference was not statis-tically significant.Wound healing assay showed that SDF-1 and G-CSF promoted cell migration of DPSC significantly (P<0.01 ),but there was no significant difference between the two factors.In Transwell migration assay,the number of migrated cells of the control group was 5 .0 ±1 .4 per sight,while the SDF-1 group was 24.3 ±6.8 per sight and the G-CSF group was 1 1 .8 ±3.3 per sight,suggesting that cell migration of DPSC was improved significantly after being treated with SDF-1 or G-CSF,and SDF-1 was more effective than G-CSF (P<0.05 ).Significantly greater odontoblastic differentiation potential was found in SDF-1 group and G-CSF group based on the ALP staining.Higher ALP activity,more mineralization nodule formation and higher expressions of DMP-1 and DSPP were also found after SDF-1 or G-CSF treatment.Conclusion:SDF-1 had no significant effect on the proliferation of DPSC,but could significantly promote cell migration and odontoblastic differentiation of DPSC.Its effect on DPSC was bet-ter than G-CSF.

Objective To explore the febrile response and placental pathological inflammation of pregnant rats exposed to intrauterine infection in late gestation.Methods Pregnant Sprague-Dawley rats at gestational day 18 were randomly divided into control group and intrauterine-infected group with six rats in each.The intrauterine-infected group was intraperitoneally injected with 350 μ g/kg lipopolysaccharide to establish a rat model of intrauterine infection,while the control group was injected with sterile saline of the same dose.Core temperature was measured every 1 h after intraperitoneal injection of lipopolysaccharide or saline for 8 h.At gestational day 19,after anesthesia,the placentas were taken and stained with HE.The expression levels of tumor necrosis factor-α,interleukin-6,and interleukin-1β in the placenta were determined by enzyme linked immunosorbent assay.Student t test was used for statistical analysis.Results (1) There was no temperature difference between the two groups before experimental treatment (P ＞ 0.05).Core temperature was increased 1 h after the lipopolysaccharide injection,reaching (37.67 ±0.08) ℃.The increase of temperature was significant compared with the control group [(37.13 ± 0.08) ℃,t=10.178,P ＜ 0.01].Fever was lowered 2 h later and the rats became hypothermic with body temperature below 37 ℃ in the intrauterine-infected group.The body temperature in the intrauterine-infected group after 2-6 h was (37.70 ± 0.10),(37.23 ± 0.05),(36.57 ± 0.06),(36.60 ± 0.10) and (36.57 ± 0.08) ℃,respectively,compared with the control group [(36.83 ±0.12),(36.63 ± 0.12),(36.71 ± 0.07),(36.87±0.12),and (36.77±0.08) ℃,respectively],the differences being all statistically significant (t=11.402,11.163,-4.025,-4.000 and-4.243,all P ＜ 0.01).(2) HE staining revealed large amounts of neutrophils infiltration,vascular enlargement and congestion in the placenta of the intrauterine-infected rats.No inflammatory cell infiltration was observed in the control placentas.(3) The expression levels of proinflammatory cytokine tumor necrosis factor-α [(0.62 ± 0.02) ng/g],interleukin-6 [(66.12 ± 5.11) ng/g],and interleukin-1β [(7.09± 1.23) ng/g] in the intrauterine-infected group were higher than those in the control group [(0.27±0.01),(16.71 ±1.55) and (2.86 ± 0.38) ng/g,respectively].The differences were all statistically significant (t=-26.608,-18.749 and-5.714,all P ＜ 0.01).Conclusion After exposure to lipopolysaccharide in late gestation,pregnant rats show significant inflammatory response in the placenta,with suppression of febrile response and presence of hypothermia.

BACKGROUNDCesarean scar pregnancy (CSP) is a very rare but life-threatening entity and there is no optimal management strategy. Here we report a successfully conservative treatment of CSP.

METHODSWe retrospectively analyzed the clinical data of 54 women with CSP, who underwent uterine artery embolization between January 2007 and September 2012 at the Peking University People's Hospital. We evaluated the clinical outcomes, the technique and the complications of uterine artery embolization.

RESULTSOf the 54 patients, 2 patients with hemorrhage after induced abortion received bilateral uterine artery embolization treatment alone, and 52 patients underwent suction curettage after bilateral uterine artery embolization. All 54 women were successfully cured, without any severe complications, and uterine function was restored. During the follow-up, one patient had accidental normal interuterine pregnancy and received induced abortion during the first trimester.

CONCLUSION[corrected] Uterine artery embolization combined with suction curettage is an effective and safe conservative treatment for cesarean scar pregnancy.