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

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the effects of external application of Sanying Plaster on the size of thyroid nodules and the states of depression and anxiety in patients with benign thyroid nodules.Methods:A randomized controlled trial was conducted. A total of 120 patients with benign thyroid nodules from the outpatient clinic of the Department of Thyroid Diseases at Shanghai Traditional Chinese Medicine Hospital from June to December 2022 were selected as the subjects of the study. They were divided into two groups using the random number table method, with 60 patients in each group. The control group received lifestyle intervention treatment, while the treatment group received Sanying Ointment in addition to the treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were measured before and after treatment; the maximum diameter of thyroid nodules was measured using a color Doppler ultrasound transverse section; the quality of life was assessed using the short form 36 (SF-36); the degree of anxiety and depression was evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS); adverse reactions during the treatment period were recorded, and the clinical efficacy was evaluated.Results:During the treatment period, 4 cases in the treatment group and 3 cases in the control group did not complete the treatment. Finally, 56 cases in the treatment group and 57 cases in the control group entered the efficacy evaluation. The total effective rate of the treatment group was 71.4% (40/56), and that of the control group was 14.0% (8/57), with a statistically significant difference between the two groups ( χ2=26.82, P<0.001). After treatment, the TCM syndrome score of the treatment group (10.02±3.65 vs. 16.65±3.44, t=-10.24) was lower than that of the control group ( P<0.001); the maximum diameter of thyroid nodules [11.00 (4.65, 19.93) mm vs. 15.00 (7.15, 28.50) mm, Z=-2.43] was lower than that of the control group ( P<0.05); the SF-36 score [121.83 (117.00, 130.00) vs. 114.42 (104.25, 127.50), Z=-2.62] was higher than that of the control group ( P<0.01); the SDS (46.72±4.59 vs. 57.02±5.99, t=14.80) and SAS (42.25±5.72 vs. 50.60±7.12, t=10.04) scores were lower than those in the control group ( P<0.001). The incidence of adverse reactions during the treatment period in the treatment group was 3.5% (2/57), and no adverse reactions occurred in the control group. Conclusion:The external application of Sanying Ointment helps to reduce the size of thyroid nodules in patients with benign thyroid nodules, improve the quality of life and anxiety and depression, and increase clinical efficacy with good safety.

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

Objective: To investigate adolescent haze weather health protection behavior, and to provide scientific basis for behavioral intervention and health guidance for adolescents in haze weather. Methods: From June 2015 to April 2016, 1 025 adolescents were selected from 22 classes in two middle schools of Baoding City, Hebei Province, by stratified cluster sampling method. General information questionnaire and the Brief Haze Weather Health Protection Behavior Assessment Scale Adolescent Version (BHWHPBAS AV) were used. Multiple linear regressions were conducted to explore factors affecting adolescent haze weather health protection behavior. Different models were used to confirm associations between influencing factors and BHWHPBAS AV scores. Results: Adolescents had a low overall score of BHWHPBASAV (45.81±13.16). The score rate of self adjustment after haze weather was the highest (64.54%). The score rate of obtaining relevant knowledge before haze weather was the lowest (50.28%). Compared with adolescents in urban area, rural adolescents had a lower BHWHPBAS AV score ( β=-3.20, P <0.01). Compared with students (living with parents), those living without parents had a lower BHWHPBAS AV score ( β=-4.16, P =0.01). Compared with students never receive physical examination,those had received physical examination during the past years had a higher BHWHPBAS AV score ( β=4.44，5.66，9.04, P <0.01). Compared with students with no knowledge of respiratory system diseases, those with moderate to sufficient knowledge had a higher BHWHPBAS AV score ( β=9.34，12.19，P <0.01). These associations were stable and consistent.Multiple linear regression analysis showed that residence, residence with parents, physical examination and knowledge of respiratory diseases were the relevant factors of BHWHPBAS AV score ( P <0.05). Conclusion Adolescent haze weather health protection behavior level is low and is affected by many factors. Cooperation should be strengthened to conduct behavioral interventions and health guidance on haze health protection for adolescents, so as to promote healthy growth of adolescents.

Objective:To investigate the clinical characteristics and possible mechanisms of remote intracranial hematoma (RIH) in patients with intracranial aneurysm after interventional embolization.Methods:Six patients with RIH from a series of 58 consecutive patients with intracranial aneurysm, admitted to and performed interventional embolization in our hospital from January 2016 and December 2018, were chosen in our study. Their clinical data were analyzed retrospectively and compared with those without RIH at the same period.Results:In these 6 patients, 4 had history of hypertension, 5 had aneurysm located in the internal carotid artery, 5 were treated with stents combined with postoperative routine anticoagulation treatment. The remote intracranial hematoma occurred within 7 d of interventional embolization, and the hematoma was located in the cerebral hemisphere on the same side of the aneurysm; 4 patients underwent intracranial hematoma puncture catheter drainage; 1 patient was treated conservatively, and one was treated by craniotomy. After treatment, 1 patient recovered (modified Rankin scale [mRS] score of 1), 1 patient had poor prognosis (mRS scores of 5) and discharged automatically, and the rest 4 patients (mRS scores of 3-5) left some degrees of neurological dysfunction. As compared with 52 patients without RIH, 6 patients with RIH had significantly higher percentages of patients used stents and postoperatively used anticoagulation, and higher percentages of patients with poor clinical outcomes at discharge ( P<0.05). Conclusion:Stent-assisted coil embolization in patients with internal carotid artery aneurysm combined with hypertension should be highly vigilant about the possibility of RIH.

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

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 evaluate the clinical effect of fire needle in treating vitiligo and the characteristics of vitiligo image by the confocal laser scanning microscope(CLSM).Methods The randomized self-controlled experiment design was adopted.Each patient selected two symmetric or adjacent white patches and randomly received the fire needle treatment or tacrolimus treatment. The duration of treatment was 3 months.The CLSM images of white patches were recorded before treatment and after 3,6 times of fire needle treatment.Results Among 41 cases of stable stage vitiligo,The effective rates of the fire needle group and tacrolimus group were 82.9% and 78.0% respectively,and the difference was not statistically significant(P>0.05).After fire needle treat-ment,dentritic melanin cells appeared,the pigment granules gradually appeared around the basal layer and corpora papillare,and formed the pigment ring.Conclusion Fire needle and tacrolimus have the similar effect in treating vitiligo,moreover CLSM can be used as the non-invasive,objective and reliable detection means of the recovery of vitiligo melanocyte.