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

Human parainfluenza virus（HPIV）is one of the important causes of respiratory infections in children，and it can occur year-round.There are four serotypes of HPIV，each with both similarities and certain differences.HPIV is associated with various diseases，but currently there are no effective therapeutic drugs or targeted vaccines on the market，mainly focusing on symptomatic supportive treatment.This review summarized the epidemiology，risk factors，pathogenic mechanisms，clinical characteristics，laboratory diagnosis，treatment，and prevention of HPIV，providing a basis for the early diagnosis，treatment，and prevention of HPIV.

Objective:To explore the clinical features and risk factors of systemic lupus erythematosus(SLE) concomitant with interstitial lung disease(ILD) in children.Methods:A retrospective analysis was performed.A total of 111 hospitalized children diagnosed with SLE in the Department of Rheumatology and Immunology, Children′s Hospital of Soochow University from February 2016 to November 2018 were selected as the research subjects and divided into the SLE-ILD group(18 cases) and the SLE-non-ILD group(93 cases)according to the lung high-resolution CT manifestations. T-test and Wilcoxon rank sum test were used to compare and analyze the general situation, clinical manifestations and laboratory results.Multivariate Logistic regression was used to analyze the risk factors of SLE-ILD. Results:The prevalence of SLE-ILD was 16.2%(18/111 cases). There were significant differences between the SLE-ILD group and the SLE-non-ILD group in the course of disease [14.00 (12.00-24.25) months vs.1.00(1.00-2.00) months], the incidence of serositis [55.6%(10/18 cases) vs.8.6%(8/93 cases)], post-activity shortness of breath [83.3%(15/18 cases) vs.25.8%(24/93 cases)], nervous system damage [27.8%(5/18 cases) vs.6.5%(6/93 cases)], cardiovascular system damage [38.9%(7/18 cases) vs.9.7%(9/93 cases)], the occu-rrence of increased erythrocyte sedimentation rate [66.7%(12/18 cases) vs.31.2%(29/93 cases)], the decreased C 3[88.9%(16/18 cases) vs.62.4%(58/93 cases)], positive anti neutrophil cytoplasmic antibody (ANCA) [88.9%(16/18 cases) vs.18.3%(17/93 cases)], positive anti-Sm antibody [61.1%(11/18 cases) vs.15.1%(14/93 cases)] and anti ribonucleoprotein antibody (anti RNP antibody)[66.7%(12/18 cases) vs.16.1%(15/93 cases)](all P<0.05). Logistic regression analysis demonstrated that serositis( OR=30.535, 95% CI: 2.167-430.336, P=0.011), shortness of breath after exercise( OR=55.115, 95% CI: 1.117-2 579.852, P=0.041), positive ANCA( OR=65.090, 95% CI: 4.488-944.071, P=0.002) and positive anti-RNP antibody( OR=10.007, 95% CI: 1.362-73.500, P=0.024) were risk factors for SLE-ILD. Conclusions:The longer the course of SLE, the higher the incidence of ILD; serositis, shortness of breath after exercise, positive ANCA and positive anti RNP antibody may be risk factors for SLE-ILD.

Objective:To compare the clinical characteristics and etiology changes of patients with bronchiolitis before the pandemic of coronavirus disease 2019(COVID-19)with those after the pandemic, and to provide a basis for the clinical diagnosis, treatment and prevention of bronchiolitis.Methods:Retrospective analysis were made on the clinical characteristics and etiological changes of patients who were hospitalized with bronchiolitis in the Department of Pulmonology, Children′s Hospital of Soochow University before COVID-19 pandemic(from February 1, 2019 to January 31, 2020, called as Group 2019-2020)and after COVID-19 pandemic(from February 1, 2020 to January 31, 2021, called as Group 2020-2021). Medical records were reviewed to compare general conditions, clinical manifestations, and laboratory tests.Nasopharyngeal secretion examination results were collected to compare the differences in pathogenic composition.Results:A total of 285 patients were enrolled in the Group 2019-2020, while 190 patients in the Group 2020-2021.There were no significant differences in gender, age, symptom duration prior to admission and length of stay between the two groups( P>0.05). The proportion of moderate/severe cases in the Group 2020-2021 was lower than that in the Group 2019-2020[10.53%(20/190)vs 21.75%(62/285)]and the difference was statistically significant( χ2=10.062, P<0.05). The proportion of stuffy nose rhinorrhea in the Group 2020-2021 was higher than that in the Group 2019-2020, while the proportion of gastrointestinal symptoms(vomiting and diarrhea)in the Group 2020-2021 was lower than that in the Group 2019-2020 [57.37%(109/190)vs 47.37%(135/285)and 15.79%(30/190)vs 24.56 %(70/285)]and the differences were statistically significant( χ2 were 4.563 and 5.278 respectively, all P<0.05). There were no significant differences in the proportions of fever, dyspnea, shortness of breath and cyanosis between the two groups(all P>0.05). The creatine kinase isoenzyme(CK-MB)in the Group 2020-2021 was lower than that in the Group 2019-2020[4.15(2.90~5.60)vs 6.70(4.20~22.10)]and the difference was statistically significant( Z=-8.757, P<0.05). There were no statistically significant differences in white blood cell count(WBC), percentage of neutrophil(N%), blood platelet count(PLT), percentage of eosinophil(EOS%), C-reactive protein(CRP), alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)between the two groups(all P>0.05). The total pathogen detection rate, positive rate of respiratory syncytial virus(RSV), positive rate of mycoplasma pneumoniae(MP)and mixed infection rate in the Group 2020-2021 were lower than those in the Group 2019-2020[65.26%(124/190)vs 75.09%(214/285), 14.21%(27/190)vs 30.18%(86/285), 6.32%(12/190)vs 15.09%(43/285), 16.84%(32/190)vs 25.61%(73/285)], with statistically significant differences( χ2 were 5.361, 16.026, 8.568 and 5.094 respectively, all P<0.05). The positive rate of rhinovirus in the Group 2020-2021 was higher than that in the Group 2019-2020[13.16%(25/190)vs 4.91%(14/285)]and the difference was statistically significant( χ2=10.285, P<0.05). There were no significant differences in the positive rates of human metapneumovirus, Boca virus and parainfluenza virus 3 between the two groups(all P>0.05). Conclusion:The clinical characteristics and etiology of patients with bronchiolitis have changed after the COVID-19 pandemic.The quarantine and protection measures reduce the transmission of associated pathogens and the severity of the disease.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:To investigate the clinical characteristics and risk factors of bronchiolitis obliterans (BO) after adenovirus pneumonia.Methods:Clinical data of 266 children with adenovirus pneumonia hospitalized in Children′s Hospital of Soochow University from January 2011 to December 2017 were retrospectively analyzed.Accor-ding to whether they developed BO, children with adenovirus pneumonia were divided into the BO group and the non-BO group.Clinical features of the BO group and the non-BO group were compared by t test, rank sum test or chi square test.Risk factors were analyzed by Logistic regression approach. Results:Among 266 children with adenovirus pneumonia included, 37 patients were developed into BO group, and their age was significantly younger than that of the non-BO group [12.0(8.0, 17.5) months vs.32.0(13.0, 48.0) months, P<0.001]. Compared with the non-BO group, there were more proportion of preterm infants[10.8%(4/37 cases) vs.3.1%(7/229 cases), P=0.028], more instances of comorbidities [21.6%(8/37 cases) vs.4.4%(10/229), P<0.001] and more children with allergic diseas[35.1%(13/37 cases) vs.20.1%(46/229 cases), P=0.041] in the BO group, and the difference was statistically significant.The duration of fever in the BO group was significantly longer than that of the non-BO group [10(4.0, 13.5) d vs.6(4.0, 9.0) d, P=0.011] children with symptoms of wheezing, shortness of breath, and hypoxemia in the BO group were significantly more than the non-BO group[81.1%(30/37 cases) vs.27.9%(64/229 cases), P<0.001; 64.9%(24/37 cases) vs.5.7%(13/229 cases), P<0.001; 59.5%(22/37 cases) vs.6.6%(15/229 cases), P<0.001]. The platelet count, IgG level, and CD3 -CD 19+ lymphocyte percentage were significantly higher in the BO group than the non-BO group [(364±104)×10 9/L vs.(297±105)×10 9/L, P=0.001; 6.74(4.92, 10.16) g/L vs.5.93(1.00, 8.04) g/L, P=0.016; (33.5±15.3)% vs.(26.1±10.2)%, P=0.008]. In contrast, the percentage of CD3 + CD4 + lymphocytes in the BO group was lower than the non-BO group[(29.1±8.0)% vs.(32.5±9.4)%, P=0.044], the difference was statistically significant.The BO group had a higher rate of mixed bacterial infection than the non-BO groups[37.8%(14/37 cases) vs.16.6%(38/229 cases), P=0.003]. An age<26 months, comorbidities, premature birth history, wheezing, shortness of breath, and hypoxemia were independent risk factors for BO after adenovirus pneumonia( OR=4.808, 30.667, 7.558, 3.909, 8.842, 8.607, all P<0.05). Conclusions:An age of less than 26 months, a history of premature delivery comorbidities, wheezing, shortness of breath and hypoxemia, are independent risk factors for BO after adenovirus pneumonia.Children with above manifestations should receive high resolution CT as soon as possible to determine whether it is BO.

Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and its risk factors in children. Methods: This study was conducted on patients with bronchiolitis admitted to the Department of Respiratory Disease, Children′s Hospital of Soochow University between November 2016 and March 2017.Nasopharyngeal secretions were taken from all patients and assessed for respiratory pathogens.After discharge, the patients were followed up every 3 months by outpatient visit or telephone call for 1 year. Results: Eighty-nine patients with bronchiolitis were enrolled in this study.Among those 89 patients, respiratory syncytial virus(RSV) infection accounted for 46.1%(41/89 cases), Mycoplasma pneumonia(MP) for 5.6%(5/89 cases), rhinovirus(RV) for 4.5%(4/89 cases), and human bocavirus(hBoV) for 2.2%(2/89 cases). Eighty-three patients were successfully followed up.At the 3, 6, 9, and 12 months of follow-up, the occurrence of wheezing episodes for only once happened in 20 cases(24.1%), 27 cases(32.5%), 35 cases (42.2%), and 38 cases(45.8%), respectively.At 12 months after initial bronchiolitis, the occurrence of wheezing episodes for only once happened in 21 cases(25.3%), 2 episodes of wheezing in 10 cases(12.0%), and 7 cases (8.4%) had more than 3 episodes of wheezing, and 6 cases lost follow-up.The proportion of eczema and milk-protein allergy in post-bronchiolitis recurrent wheezing group was significantly higher than that of the group with not post-bronchiolitis recurrent wheezing patients (χ²=6.219, 4.855, all P<0.05). Logistic regression analysis showed eczema was the independent risk factor for post-bronchiolitis recurrent wheezing(OR=0.189, 95%CI: 0.047-0.765). There were no significant difference in gender, age, premature birth, birth weight, feeding pa-tterns, family history of asthma, pet contact history, severity of disease, course of disease, total immunoglobulin E of serum and the species of virus infected between 2 groups(all P>0.05). Conclusions The incidence of recurrent wheezing among post-bronchiolitis patients is higher during one-year follow-up period.Eczema is the independent risk factor for post-bronchiolitis recurrent wheezing.The specific pathogens and severity of disease have no correlation with post-bronchiolitis wheezing.

OBJECTIVE: To explore association of the expression levels of adenylate cyclase-associated protein 2 (CAP2) in gastric cancer tissues with the histopathology and long-term prognosis of the malignancy. METHODS: This study was conducted among a total of 105 patients with gastric cancer undergoing radical gastrectomy in our hospital between January, 2010 and October, 2013. Immunohistochemistry was used to quantitatively assess the expression of CAP2 in gastric cancer tissues and the adjacent tissues. Based on the median relative expression level of CAP2 of 3.5, the patients were divided into low CAP2 expression group (=52) and high CAP2 expression group (=53). The Cox regression model was used to analyze the effect of CAP2 expression on the 5-year survival rate of the patients, and ROC curve analysis was used to assess the predictive value of CAP2 expression for the patients' long-term survival. RESULTS: Immunohistochemical analysis showed that the expression levels of CAP2 ( < 0.01) and Ki67 ( < 0.01) were significantly higher in gastric cancer tissues than in the adjacent tissues, and the expression level of CAP2 was positively correlated with Ki67 ( < 0.01), peripheral blood CEA ( < 0.01) and CA19-9 ( < 0.01). The percentages of patients with CEA≥5 μg/L, CA19-9≥37 kU/L, pathological grade of G3-G4, T stage of 3-4, and N stage of 2-3 were significantly higher in patients with high CAP2 expression than in those with low CAP2 expression ( < 0.05). Kaplan- Meier survival analysis showed that the 5-year survival rate was significantly lower in patients with a high CAP2 expression ( < 0.01). A high expression level of CAP2, CEA≥5μg/L, CA19-9≥37 and pathological grades G3-G4 were all independent risk factors for shortened 5-year survival after radical gastrectomy ( < 0.01). With the relative expression level of 3.45 as the cut-off value, the sensitivity of CAP2 was 70.15% for predicting death 5 years after the surgery, with a specificity of 71.05% and an area under the curve of 0.779 ( < 0.01). CONCLUSIONS CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer and can be of clinical value in prognostic evaluation of the patients.
Adaptor Proteins, Signal Transducing ; metabolism ; Gastrectomy ; Humans ; Immunohistochemistry ; Membrane Proteins ; metabolism ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; metabolism ; pathology ; Survival Rate

OBJECTIVE: To investigate the protective effect of procyanidin B2 (PCB2) on the intestinal barrier and against enteritis in mice with trinitrobenzene sulphonic acid (TNBS)-induced colitis and explore the possible mechanism. METHODS: A mouse model of TNBS-induced colitis was established in male Balb/c mice aged 6-8 weeks. The successfully established mouse models were randomly divided into PCB2 treatment group (=10) and model group (=10) and were treated with daily intragastric administration of PCB2 (100 mg/kg, 0.2 mL) and 0.2 mL normal saline, respectively. After 4 weeks, the disease symptoms, intestinal inflammation, intestinal mucosal cell barrier function and the changes in PI3K/AKT signaling were evaluated using HE staining, immunofluorescence assay and Western blotting. RESULTS: The disease activity index of the mice was significantly lower and the mean body weight was significantly greater in PCB2 group than in the model group in the 3rd and 4th weeks of intervention ( < 0.05). The levels of colonic inflammation and intestinal mucosal inflammatory mediators IL-1β and TNF-α were significantly lower while IL-10 was significantly higher in PCB2 group than in the model group ( < 0.05). Compared with those in the model group, the mice in PCB2 treatment group showed a significantly lower positive rate of bacterial translocation in the mesenteric lymph nodes and a lower thiocyanate-dextran permeability of the intestinal mucosa ( < 0.05). Western blotting showed that PCB2 treatment significantly increased the expressions of claudin-1 and ZO-1 ( < 0.05) and significantly lowered the expression levels of p-PI3K and p-AKT in the intestinal mucosa as compared with those in the model group ( < 0.05). CONCLUSIONS PCB2 suppresses intestinal inflammation and protects intestinal mucosal functions and structural integrity by inhibiting intestinal PI3K/AKT signaling pathway, suggesting the potential of PCB2 as a new drug for Crohn's disease.
Animals ; Biflavonoids ; Catechin ; Colitis ; chemically induced ; Colon ; Enteritis ; Intestinal Mucosa ; Male ; Mice ; Phosphatidylinositol 3-Kinases ; Proanthocyanidins ; Trinitrobenzenesulfonic Acid