Objective: This study investigated the effect of applying different torque values on the sagittal displacement tendency of mandibular incisors during intrusion using clear aligners, with the aim of providing a reference for achieving true vertical intrusion (intrusion without labiolingual movement) of mandibular incisors in clear aligner therapy. Methods: This study was approved by the institutional ethics committee. A volunteer with an incisor mandibular plane angle of 94° was selected. Using cone-beam computed tomography and intraoral scan data, a high-precision three-dimensional finite element model was established. An intrusion amount of 0.2 mm was set for the mandibular incisors, and four simulation groups were defined by applying 0°, 1°, 2°, and 3° of root labial torque. The displacement tendency of the incisors and the stress distribution within the periodontal ligament were analyzed. Results: When 0° of root labial torque was applied, the mandibular incisors exhibited intrusion accompanied by crown-labial, root-lingual inclination. When 1°-3° of root labial torque was applied, the mandibular incisors exhibited intrusion accompanied by the inclination gradually shifted from crown-labial, root-lingual towards crown-lingual, root-labial. Based on the line graph of sagittal displacement, the central incisors and lateral incisors approximated true vertical intrusion when 1.8° and 2.5° of root labial torque was applied, respectively. The mandibular canines consistently exhibited extrusion accompanied by labial crown inclination. Stress within the periodontal ligament of the incisors and canines was primarily concentrated at the root apex and cervical region. After applying root labial torque, the area of stress concentration in the incisors cervical periodontal ligament shifted from the labial side to the lingual side. The stress in the periodontal ligament at the cervical region of the canines is predominantly concentrated on the labial side. Conclusion Applying appropriate torque control during mandibular incisor intrusion with clear aligners facilitates true vertical intrusion, thereby enhancing the efficiency of the intrusion.

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 explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

This report describs 2 domestic cases of tacrolimus poisoning in kidney transplant recipients due to overexposure of tacrolimus caused by nirmatrelvir/ritonavir for SARS-CoV-2 infection.Phenytoin sodium is prescribed for inducing CYP3A enzyme.It is intended for providing references for formulating and adjusting treatment protocols for tacrolimus overexposure and related toxicity in kidney transplant recipients caused by nirmatrelvir/ritonavir.

Objective:To explore the clinical characteristics and outcomes of pediatric kidney transplantations at a single center and discuss the related clinical issues.Methods:From January 1990 to October 2019, clinical data were analyzed retrospectively for 244 pediatric renal transplants. The youngest recipient was aged 1.8 years and the median age of pediatric recipients was 12.2 years. The major disease was primary or hereditary glomerulonephritis ( n=160, 69.0%), congenital anomalies of kidney and urinary tract (CAKUT), cystic renopathy and other hereditary nephropathies ( n=55, 23.7%). The donor sources included traditional deceased donor ( n=42, 17.2%), living-related donor ( n=19, 7.8%) and organ donation ( n=183, 75.0%). The median age of donors was 2 years (0-51) and the median weight 12.0(2.7-72.0) kg. From January 2013 to October 2019, 170 cases), the major induction immunosuppression regimen was anti-thymocyte globulin (ATG) ( n=110, 64.7%) or basiliximab ( n=58, 34.1%). The maintenance regimen was tacrolimus + mycophenolic acid (MPA) + glucocorticosteroids. Finally the outcomes and the complications were analyzed. Results:The survival rates of 244 kidney allograft recipients were 98.1%, 94.5% and 93.4% and the graft survival rates 92.6%, 84.2% and 82.0% at 1/3/5 years respectively. Ten recipients died of accident ( n=2, 20.0%), pneumonia after transplantation ( n=2, 20.0%) and intracranial hemorrhage ( n=2, 20.0%). Thirty-three recipients lost their allografts mainly due to intravascular thrombosis in graft ( n=5, 14.3%), acute rejection ( n=5, 14.3%) and death ( n=9, 25.7%). Besides, among 109 deceased donor allograft recipients, the postoperative outcomes were delayed graft function recovery (DGF) ( n=27, 24.8%), arterial thrombosis ( n=6, 5.5%), venous thrombosis ( n=1, 0.9%), graft perirenal hematoma ( n=6, 5.5%), raft artery stenosis ( n=10, 9.2%) and graft ureteral fistula ( n=1, 0.9%). The incidence of acute rejection was 17.5% and 23.2% at 1/3 year respectively. The recurrent rate of primary disease was 6.9%, including primary FSGS ( n=3, 42.9%) and IgA nephropathy ( n=2, 28.6%). At 1/3 year post-operation, the incidence of pulmonary infection was 16.9% and 22.4% and the incidence of urinary tract infection 26.9% and 31.7%. Excluding recipients with graft failure, the estimated glomerular filtration rate (eGFR) at 1/2/3 year postoperatively was (80.3±25.2), (81.4±27.8) and (71.8±27.6) ml/(min·1.73 m 2)respectively. Conclusions:The outcomes of pediatric renal transplantations are excellent at our center. Future efforts shall be devoted to optimizing the strategies of donor kidney selection and strengthening preoperative evaluations, perioperative and postoperative managements for improving the long-term outcomes of pediatric renal transplantations.

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 study the protective effect of shenfu injection on cerebral ischemia reperfusion injury in rats.Methods 120 male Sprague Dawley (SD) rats(320-350 g) were randomly divided into sham operation group,model control group,Nimodipine injection group,low,medium and high dose group of shenfu injection according to gender weight.20 males in each group were given medicine once a day for 7 days before operation.The cerebral ischemia model was established by thread embolization after 5 days of administration.In the sham operation group,the other operations were the same as those in the model group except for carotid artery ligation and thread insertion.After 24 hours of perfusion,the neurological score,abdominal aorta blood flow,malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione (GHS) levels in brain tissues were measured.Triphenyltetrazolium chloride (TTC) staining was used to calculate the area of cerebral infarction and pathological examination of brain tissues.Results Compared with the model control group,the middle and high dosage of shenfu injection could obviously improve the nerve function and increase the percentage of cerebral infarction area (P ＜ 0.05);the high dosage group of shenfu injection could obviously decrease the whole blood viscosity (P ＜ 0.01);the middle and high dosage of shenfu injection could obviously reduce the level of MDA in rat brain tissue (P ＜ 0.01) while increasing the levels of SOD and GSH (P ＜0.01),finally could significantly improve the pathological changes of brain tissues such as mild swelling of nerve fibers,mild neuronal degeneration,inflammatory interstitial edema and inflammation.Conclusions Shenfu injection has obvious protective effect on cerebral ischemia reperfusion model in rats.

Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t-test or the Mann-Whitney test. χ ²-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD (HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD (HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.

Objective To study the correlation between non-alcoholic fatty liver disease (NAFLD)and glycosylated hemoglobin (HbA1 c) in middle-aged and aged population.Methods A total of 4 127 inservice workers and retirees aged 45 years old or above from one petrochemical enterprise in Ningbo were enrolled in our study.The waistline,body mass index,blood pressure,fasting blood-glucose,blood lipid profile,glutamyltranspeptidase,HbA1c and epigastrium B ultrasound were investigated.According to the quartile of HbA1c level,participants were divided into four groups,namely,Q1 group ≤5.2％,Q2 group ＞ 5.2％-5.4％,Q3 ＞ 5.4％-5.6％ and Q4 group ＞ 5.6％.The prevalence of NAFLD and clinical characteristics of each group were analyzed.Logistic regression was used to predict independent risk factors of NAFLD.Results The morbidity of NAFLD was 27.2％ with 31.9％ in male and 21％ in female,which was significantly higher in men.In Q1,Q2,Q3 and Q4 group,the prevalence of NAFLD were 18.5％ (178/961),22.8％ (185/812),25.6％ (280/1 095),38.1％ (480/1 259) respectively.With the increase of HbA1 c level,the morbidity of NAFLD increased synchronously.The age,systolic pressure,total cholesterol,low densitylipoprotein cholesterin and fasting blood-glucose were all elevated according to the increase of HbA1 c in 1 123 NAFLD patients.Multi-factor logistic regression analysis indicated that high HbAlc level was the risk factor of NAFLD (OR =1.67,95％ CI 1.15-2.43,P =0.007).Conclusion HbA1c is an independent risk factor of NAFLD and both of these are closely related to blood lipid metabolism disorder.

Objective To explore the relationship between thyroid hormone and colorectal adenomatous polyps (CAP) in middle-aged and elderly people.Methods We surveyed 3 042 middle-aged employees and retirees aged 45 years and over at a petrochemical enterprise of Ningbo.Their colonoscopic findings,body mass index,waist circumference and thyroid function were analyzed.Results Age and serum free triiodothyronine (FT3) of females with CAP were higher than those of the corresponding non-CAP group,so were age and waist circumference of males with CAP (P ＜ 0.05).Furthermore,these differences were statistically significant.The detection rate of CAP was significantly higher in males than in females (x2 =49.418,P ＜ 0.01).The detection rate of CAP was higher in females with higher levels of FT3.Multivariate unconditional logistic regression analyses showed the effects of thyroid hormone on the CAP differed by gender.Age and FT3 (OR =1.60,95％ CI:1.12-2.28,P =0.01) were correlated with CAP in females.However,only age and waist circumference were correlated with CAP in males.Conclusion Elevated FT3 may be a risk factor of CAP in elderly females.The detection rate of CAP may not be affected by FT3 levels in males.