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:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Fiber photometry is a sensitive and easy way to detect changes in fluorescent signals. The combination of fiber photometry with various fluorescent biomarkers has substantially advanced neuroscience research over the last decade. Despite the wide use of fiber photometry in biomedical fields, the lack of a detailed and comprehensive protocol has limited progress and sometimes complicated the interpretation of data. Here, we describe detailed procedures of fiber photometry for the long-term monitoring of neuronal activity in freely-behaving animals, including surgery, apparatus setup, data collection, and analysis.
Animals ; Brain ; metabolism ; Calcium Signaling ; Female ; Male ; Mice ; Neurons ; metabolism ; Neurosurgical Procedures ; Optical Fibers ; Optical Imaging ; instrumentation ; methods ; Photometry ; instrumentation ; methods

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.

Objective To compare the safety and efficacy of minimally-access percutaneous nephrolithotomy (Mini-PCNL) in modified lateral position and prone position in high-risk patients with upper urinary tract stones and explore the clinical value of the modified lateral position. Methods We retrospectively analyzed 82 cases of high-risk patients underwent ultrasound-guided percutaneous nephrolithotomy from June 2010 to December 2015. 43 cases in group of modified lateral position and 39 case in group of prone position. The mean operating time, the success rate of stone fragmentation, hospitalization days, the value of postoperative hemoglobin decline and complication rate of patients were record and compared between the two groups. Results There was no statistical significance between the modified lateral position group and prone position group (P > 0.05) in gender, age, stone type, BMI, the score of ASA and preoperative complication. There was statistical significance in found access time, (7.88 ± 0.82) min in the modified lateral position group and (8.50 ± 0.80) min in the prone position group (P < 0.01). The stone free rate in the modified lateral position group (95.35 %) was higher than that in prone position group (74.36 %), the value of postoperative hemoglobin decline were (9.33 ± 2.49) g/L and (10.90 ± 3.54) g/L, respectively (P < 0.05); Two groups of the pleural damage rate had significant difference (P < 0.05); the hospitalization days and operating time were no statistical difference between the two groups (P > 0.05). Conclusions The Mini-PCNL in modified lateral position for high-risk patients had advantages of found access time, stone clearance rate, pleural injury, blood loss, comfort degree and security and worthy of clinical promoting.

Objective To investigate the hemodynamic parameters to stabilize cerebral blood flow within limits of cerebral autoregualtion. Methods We assessed the flow velocity of middle cerebral artery using transcranial Doppler and recorded invasively the blood pressure simultaneously. We then analyzed the curves of cerebral blood flow autoregulation (CBFA) and calculated upper limit of autoregulation (ULA) and lower limit of autoregulation (LLA). The values of critical closing pressue (CCP) and resistance area product (RAP) were calculated according to previous theory. The relationship between CCP, RAP and MABP were analyzed. Results In the process of increasing or decreasing blood pressure, ULA and LLA of normal rats were 148.12 ± 7.49 mmHg or 62.96 ± 3.34 mmHg, respectively. When mean artery blood pressue (MABP) changed within limits of cerebral autoregulation, the cerebral blood flow velocity changed little (increasing:0.65± 0.27 cm/s/10mmHg MABP, decreasing:0.43±0.23cm/s/10 mmHg MABP), while CCP and RAP changed significantly (in?creasing: 4.60 ± 1.06 mmHg/10mmHg MABP and 0.11 ± 0.04/10 mmHg MABP, decreasing: 6.74 ± 0.59 mmHg/10 mmHg MABP and 0.09 ± 0.02/10mmHg MABP). After fixing change of blood flow velocity, CCP and RAP were correlated with MABP more remarkablely, although all blood flow velocity, CCP and RAP were significantly correlated with MABP. Conclusion Within limits of cerebral autoregulation, stable cerebral blood flow is mainly achieved by the change of CCP and RAP against blood pressure changing on normal rats, especially the increasing or de?creasing of CCP.

Objective To observe the effects of electroacupuncture on the expressions of autophagy related protein Beclin-1 and apoptosis related protein p53 of hippocampus in rats;To explore the mechanism of electroacupuncture on Alzheimer's disease (AD).Methods The rats were randomly divided into the normal group, the sham-operation group, the model group, and the electroacupuncture treatment group. “Baihui” and “Yongquan” points were taken for electroacupuncture treatment and the treatment course was 7 days. The rats were treated once a day for 4 courses. Changes in morphology and number of Nissl positive cells were examined by Nissl staining in hippocampal CA1 regions. Expressions of Beclin-1 and p53 protein were determined by Western blot analysis.Results Number of Nissl positive cells in CA1 region of the model group was significantly less than that of normal group (P<0.01). After electroacupuncture treatment, number of pyramidal cells and expression of Nissl body significantly increased (P<0.05). Expression of Beclin-1 decreased, while expression of p53 increased in the hippocampus of the model group, compared with that in the normal group (P<0.05). However, electroacupuncture treatment could significantly upregulate the expression of Beclin-1 protein (P<0.01), but downregulate the level of p53 (P<0.05).Conclusion Electro-acupuncture treatment could fight against Aβ-induced neuronal apoptosis, and improve the morphological changes of AD’s hippocampus.