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 analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.

Delayed graft function in kidney transplant recipients is one of the common early complications after kidney transplantation,which is an independent risk factor affecting the short-term and long-term survival of renal allografts.Branch of Organ Transplantation of Chinese Medical Association and Branch of Kidney Transplantation of China International Exchange and Promotive Association for Medical and Health Care organized well-known Chinese experts in organ transplantation and related disciplines to formulate and discuss the determination of the scope and clinical problems,evidence retrieval and screening,and the formation of recommendations based on"Technical Specification for the Diagnosis and Treatment on Delayed Graft Function After Renal Transplantation(2019 edition)".After two rounds of collective examination and approval by Chinese Medical Association and China International Exchange and Promotive Association for Medical and Health Care,"Guidelines for Clinical Diagnosis and Treatment of Delayed Graft Function in Kidney Transplant Recipients in China"was finally formulated.This guideline puts forward recommendations and explanations regarding 21 clinical problems including the concept,mechanism,risk factors,diagnosis,prevention,treatment and application of immunosuppressive drugs for delayed graft function in kidney transplant recipients,aiming to standardize the diagnosis,prevention and treatment of delayed graft function in kidney transplant recipients,enhance clinical efficacy of kidney transplantation,prolong short-term and long-term survival of kidney transplant recipients and renal allografts and promote the development of the discipline of transplantation.

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 analyze the changes in lung function and inflammatory indicators such as eosino-phils(EOS),Creola bodies and exhaled nitric oxide(FeNO),and to explore their value in early diagnosing asthma. Methods One hundred and thirty-five infants with high-risk asthma were selected as an observation group who were admitted to Department of Respiratory,Childrenˊs Hospital of Soochow University from April 2016 to August 2017 due to asthmatic bronchitis and asthmatic bronchopneumonia,and a total of 200 non -asthmatic and non -allergic healthy children who were screened and followed up at the Department of Cardiology in the same period were selected as a healthy control group for the measurement of moist respiratory lung function and FeNO. In the observation group,the bronchial dilation test(BDT),EOS and Creola bodies were performed simultaneously. Classification of lung function:23%≤time to peak ratio(TPTEF/Te)<28% had mild obstruction,15%≤TPTEF/Te<23% had moderate obstruc-tion,and TPTEF/Te<15% showed severe obstruction. Results The TPTEF/Te[17. 20%(8. 10%)],volume to peak ratio(VPEF/Ve)[21. 20%(6. 20%)],tidal volume per kilogram of body weight(VT/kg)[7. 80(3. 70)]and ratio of tidal expiratory flow 25% to peak tidal expiratory flow(25/PF)[0. 54(0. 20)]in the observation group were signifi-cantly lower than those in the healthy control group[22. 30%(9. 22%),27. 15%(7. 10%),8. 90(3. 17),0. 60 (0. 18)],and the differences were statistically significant(Z＝ -6. 81,-9. 35,-3. 16,-3. 52,all P<0. 05). BDT positive rate in the mild obstruction group was 20. 00%(3/15 cases),BDT positive rate in the moderate obstruction group was 26. 56%(17/64 cases),and BDT positive rate in the severe obstruction group was 48. 72%(19/39 cases). The higher the degree of obstruction,the higher the value of BDT positive diagnosis(F＝6. 353,P<0. 05). BDT of VPEF/Ve,25/PF and TPTEF/Te were consistent and statistically significant(Kappa＝0. 78,0. 49,all P<0. 001). Ti-dal expiratory flow 50% -remaining(TEF50% -r)[(117. 86 ± 42. 16)mL/s],tidal expiratory flow 25% -remai- ning(TEF25% -r)[(82. 82 ± 35. 44)mL/s]in the second wheezing group were higher than those in the first whee-zing group[(92. 81 ± 28. 40)mL/s,(65. 22 ± 24. 93)mL/s],and the differences were statistically significant( t＝3. 34,2. 77,all P <0. 05). There was no statistically significant difference in sputum EOS,FeNO and Creola body scores among wheezing children between the first and second groups(all P>0. 05). FeNO in the observation group [3. 80(5. 43)μg/L]was significantly lower than that in the healthy control group[9. 60(11. 3)μg/L],and the diffe-rence was statistically significant(Z＝14. 56,P<0. 05). Sputum EOS had a positive correlation with blood EOS and Creola bodies(r＝0. 20,0. 21,all P<0. 05);there was no correlation between lung function parameters and inflamma-tory indices(all P>0. 05). Conclusions In the acute phase of infant asthma attack,the pulmonary function presents different degrees of obstructive ventilation dysfunction,the higher the degree of obstruction,the higher the diagnostic value of BDT. The value of single FeNO measurement is limited,and continuous dynamic monitoring may be more mea-ningful in predicting the occurrence of asthma. Detection of Creola bodies may be helpful in predicting asthma.

Objective To investigate the risk factors of single and multiple bronchoscopic lavage therapy in children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods Retrospective analysis was conducted of the clinical data of 332 RMPP children at Department of Respiratory Disease,Children's Hospital of Soochow University from January 2011 to December 2016.The patients were divided into the single group and the multiple group (≥2 times),and the correlative index were compared between the 2 groups.Logistic regression analysis was performed to analyze the risk factors of multiple bronchoscopic lavage therapy in RMPP patients.Results Among 332 children,223 cases were in the single group and 109 cases in the multiple group.Children undergoing multiple bronchoscopy had the fever duration ≥ 10 days before the bronchoscopy and course of disease ≥ 10 days before the bronchoscopy,more than those in the single group [118 cases (52.9％) vs.71 cases (65.1％),69 cases (29.6％) vs.45 cases(41.3％)],and the differences were statistically significant(all P ＜ 0.05).At the same time,the use of glucocorticoid,macrolide,glucocorticoid combined with macrolide antibiotics in the first week of illness were significantly lower in the multiple groups than those in the single group,and the differences were statistically significant (all P ＜ 0.05).In the multiple group,the percentage of neutrophils (N),C-reactive protein (CRP),CRP ＞ 44 mg/L,lactate dehydrogenase (LDH) and LDH ＞ 480 U/L were higher than those in the single group,and the differences were significant (all P ＜ 0.05).In addition,the mixed infection and pleural effusion of multiple group were higher than those of the single group.The proportion of bronchoscopy in the multiple group was higher than that of the single group.In bronchoscopy,the mucus plug blocking and mucosal erosion were more than those of the single group,and the differences were statistically significant (x2 =5.397,13.31,all P ＜ 0.05).After adjusted by multiple regression analysis,6 factors were independent risk factors for multiple bronchoscopic procedures.They were the fever duration before the bronchoscopy ≥ 10 days[odds ratio (OR) =19.504,95 ％ confidence interval (CI):7.350-51.754,P =0.000],the unuse of macrolide antibiotics in the first week of illness (OR =5.072,95％ CI:2.230-11.537,P =0.000),the unuse of glucocorticoid in the first week of illness (OR =14.051,95 ％ CI:4.755-41.522,P =0.000),CRP ＞ 44 mg/L (OR =2.638,95 ％ CI:1.356-5.133,P =0.004),LDH ＞ 480 U/L(OR =2.326,95％ CI:1.302-4.157,P =0.004) and mucosal erosion (OR =11.15,95％ CI:2.503-49.715,P =0.002).Conclusion Severe inflammatory reaction and whether or not to actively resist infection and inflammation in the early stage,were important risk factors for multiple bronchoscopic procedures.

Objective: To investigate the antiviral effect of hepatitis B virus (HBV) S gene-specific anti-gene locked nucleic acid (LNA) in transgenic mice. Methods: A total of 30 HBV transgenic mice were randomly divided into blank control group (5% glucose + liposome), unrelated sequence control group, lamivudine control group, antisense LNA control group, and anti-gene LNA group, with 6 mice in each group. The mice in the lamivudine group were given lamivudine by gavage, and LNA was injected via the caudal vein. Quantitative real-time PCR was used to measure serum HBV DNA, ELISA was used to measure serum HBsAg, RT-PCR was used to measure HBV S mRNA level in the liver, and immunohistochemistry was used to measure the level of HBsAg in hepatocytes. Results: At 3, 5, and 7 days after treatment, there were significant changes in the inhibition rates of HBV DNA (37.18%, 50.27%, and 61.46%, respectively) and HBsAg (30.17%, 44.00%, and 57.76%, respectively) achieved by anti-gene LNA (P < 0.01), and there were significant differences between the anti-gene LNA group and the other four control groups (P < 0.05). In the anti-gene LNA group, the relative mRNA expression of HBV S gene was 0.33 and the percentage of HBsAg-positive hepatocytes was 31%, which were significantly different from these two indices in the control groups (P < 0.05). There were no abnormal changes in liver/renal biochemical parameters and HE staining results. Conclusion Anti-gene LNA targeting at HBV S gene has a strong antiviral effect in transgenic mice, which provides theoretical and experimental bases for gene therapy for HBV.

OBJECTIVE:To evaluate the stability of 12 kinds of submicro emulsion in market,and screen the test method for the stability. METHODS:12 kinds of submicro emulsion in market were selected,high pressure sterilization (121 ℃,30 min), high speed centrifugation(4000 r/min,15 min),accelerated test [placing 6 months under temperature of(40±2)℃,relative hu-midity of (75 ± 5)%] were conducted to investigate the pH,particle size and other indexes,and SPSS 22.0 was used to analyze the distribution variance and chi-square test,and investigate the correlation of 3 evaluation methods. RESULTS:In terms of stabili-ty investigation,the pH value of 12 kinds of submicro emulsion decreased to some extent after accelerated test,average particle size of 6 kinds of submicro emulsion samples were greater than 300 nm,the variance of the particle size distribution of 9 kinds ap-peared in 0.05-0.15,the chi-square test results of 8 kinds distributed below 1. The average particle size of 4 kinds of submicro emul-sions changed more than 10 nm after accelerated test. In terms of stability test method,Pearson chi-square progressive significance of high pressure sterilization and accelerated test was 0.665,which was higher than 0.05,indicating there was no correlation (no significance),the stability results of high pressure sterilization can not represent the results of accelerated test;that of high speed centrifugation and accelerated test was 0.004,which was lower than 0.05,indicating stability results between high speed centrifuga-tion and accelerated test results were significantly correlated. CONCLUSIONS:The submicro emulsion in market can meet the re-quirements of stability. To a certain extent,high speed centrifugation can replace the acceleration test.

Objective To establish a method for simultaneously measuring L-citrulline and L-arginine concentration in plasma using reversed-phase high performance liquid chromatography (RP-HPLC)with ultraviolet detection,and the novel method is applied to the patients with digestive system tumor.Methods Plasma samples were deproteinized by trichloroacetic acid with heating method.Phenylisothiocyanate (PITC)was used as derivatization reagent and a gradient elution was adopted. The feasibility verification of method was carried out by detecting plasma L-citrulline and L-arginine acid concentration in 21 cases of advanced digestive tract malignant tumor patients,21 cases of non malignant tumor patients and 39 cases of healthy people.Results The linearity for L-citrulline and L-arginine ranged from 0 to at least 1 000 μmol/L.r=0.999 95 for both. The lower limits of quantification for L-citrulline and L-arginine were 0.240 μmol/L and 0.448 μmol/L respectively.The in-traday and interday coefficients of variation (CVs)were less than 3.4% and 7.2%,respectively.The average recovery rate was from 95.2% to 104.1%.The ratio of plasma L-citrulline/L-arginine in patients with digestive cancar was significantly higher than that in the healthy control group,t-test,P =0.009.The sensitivity and specificity of plasma L-citrulline/L-argi-nine ratio in the malignant tumor of digestive system were 81% and 71.4% respectively.Conclusion This method can pro-vide a reliable and efficient method for the clinical determination of the L-citrulline and L-arginine concentration in plasma. The ratio of plasma citrulline/arginine increased obviously in patients with digestive cancer,suggesting that this ratio is a more sensitive index than single concentration of L-citrulline or L-arginine when evaluating patients with digestive tumor.

Objective To explore the mediating effects of college students＇ online social support on the relationship between online self-disclosure and internet altruistic behavior.Methods Using cluster random sampling,the self-disclosure questionnaire for Chinese undergraduates with their internet friend,the online social support scale of adolescence and the internet altruistic behavior scale of undergraduates were applied to 351 college students.Results The score of college students＇ online self-disclosure,online social support and internet altruistic behavior were respectively(2.22±0.45),(2.93±0.59) and (2.04±0.46).The college students＇ online self-disclosure,online social support and internet altruistic behavior were positively correlated with each other (P＜0.01).College students＇ online self-disclosure not only predicted internet altruistic behavior directly,but also predicted internet altruistic behavior indirectly through online social support.The direct effects and indirect effects were 0.200 and 0.265.The ratio of the mediating effect on the total effect was 57％.The fit index of mediation model was x2/df=2.87,RMSEA =0.07,CFI =0.94,TLI =0.93,GFI=0.92,IFI=0.94,NFI=0.91.Conclusion The college students＇ online self-disclosure not only affects the interuet altruistic behavior directly,but also can take the same effect on online social support indirectly.