1.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
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*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
;
Immunosuppressive Agents/administration & dosage*
;
Delphi Technique
2.Tear film stability and tarsal gland morphological characteristics in myopic children
Peiyan SHI ; Jinfeng LI ; Dandan ZHANG ; Xiaoman MA ; Zhaoxia ZHAI ; Zheng SUN ; Jinling GE
Recent Advances in Ophthalmology 2024;44(2):139-142
Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25%)and 21 females(43.75%).The aver-age TMH was(0.19±0.04)mm(95%CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95%CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P<0.001).In all subjects,49 eyes(53.85%)had tarsal gland atrophy,and 37 eyes(40.66%)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged<12 years and children aged ≥12 years(both P<0.05).There was a significant difference in TMH between children with an OSDI score<13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.
3.Protein expression and clinical significance of KCTD8 gene in ductal carcinoma of the breast
Ying-Ge LIU ; Hui-Jie YANG ; Xiao-Yu ZHAI ; Ji-Min HE ; Hong-Chao LI ; Ying-Li ZHANG
Chinese Journal of Current Advances in General Surgery 2024;27(2):117-121
Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P<0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P<0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.
4.Analysis on clinical efficacy of ureteroscope-assisted laparoscopic ureteroplasty at lying and running position of healthy side in the treatment of postoperative ureteral stenosis
Hua CHEN ; Tairong LIU ; Qiuhua ZHU ; Leming SONG ; Qiliang ZHAI ; Jiaqi GE ; Jiansheng XIAO
Chinese Journal of Urology 2024;45(1):29-33
Objective:To explore the safety and efficacy of ureteroscopy-assisted laparoscopic ureteroplasty in the healthy side-lying running position for the treatment of ureteral stenosis after pelvic surgery.Methods:The data of 92 patients with ureteral stenosis after surgery admitted to Ganzhou People’s Hospital from June 2017 to February 2023 were retrospectively analysed. There were 31 male patients and 61 female patients, with an average age of (46.4±23.3) years. Of the 92 patients, 53 patients had previously undergone stone fragmentation or stone retrieval surgery for urinary system stones, 35 patients had undergone gynecologic laparoscopic surgery for gynecologic diseases, 2 patients had previous intestinal surgery, and 2 patients had undergone laparoscopic ureteral reconstruction surgery. The mean preoperative serum creatinine was (120.33±16.52) μmol/L, the mean blood urea nitrogen was (14.28 ± 2.47) mmol/L, and the mean renal pelvis dilation was (3.23±2.47) cm. All patients were placed in healthy side-lying running position with general anesthesia. The patient's lower limbs were in the oblique supine position, and the angle of the lower limbs was 60-80°. By using a transabdominal approach, the narrow section of the ureter was mobilized and excised under the guidance of ureteroscopy. The posterior wall of the ureter was sutured and a zebra guidewire was placed into the renal pelvis. An F7 double-J stent was then retrogradely advanced over the guidewire. Then the anterior wall of the ureter was anastomosed to complete the surgery. The operation time, average length of hospital stay, perioperative complications, preoperative and postoperative pyelectasis and renal function changes were recorded, and the clinical efficacy were evaluated by comparative analysis.Results:Of the 92 patients, 90 patients were successfully treated with ureterovesical anastomosis. Two patients underwent ureterovesical reimplantation because of the low position and heavy adhesion of the stenosis segment. There were no cases of conversion to open surgery or intraoperative death. The mean surgery duration was (121.52±22.35) min, the mean drainage tube indwelling time was (3.16±1.23) d, and the mean hospital stay was (6.46±2.37) d. A patient with moderate hydronephrosis exhibited postoperative urinary leakage. Two patients developed symptoms of hematuria after ambulation. Following treatment with bed rest, adequate drainage, and appropriate hemostatic medication, all patients recovered smoothly and were discharged. The double J tube was removed 3 months after operation, and the CT reexamination after extubation showed that the degree of pyelectasis was (2.52±1.54) cm, the average serum creatinine was (89.64±15.21) μmol/L, and urea nitrogen was (9.42±1.36) mmol/L, which was all significantly different from that before operation ( P<0.05). The patients were followed up for 6 to 12 months, and there was no ureteral restenosis. Conclusions:Ureteroscopic-assisted laparoscopic ureteroplasty in the healthy side-lying running position is a safe and effective surgical method for the treatment of short segment (narrow segment <3 cm) ureteral cicatrix stenosis after surgery. And this surgical method has the advantages of accurate positioning of the narrow segment, safe and convenient ureteral free, exact ureteral anastomosis, and easy placement of double J tube.
5.Current Status and Prospect of PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy in Elderly Patients with Advanced NSCLC
MAO YUNYE ; SHENG SHU ; WANG AN ; ZHAI JINZHAO ; GE XIANGWEI ; LU DI ; WANG JINLIANG
Chinese Journal of Lung Cancer 2024;27(5):367-375
The incidence of cancer is closely correlated with age,as 75%of non-small cell lung cancer(NSCLC)patients are aged at least 65 years.The availability of immune checkpoint inhibitors(ICIs)has altered the available NSCLC therapeutic pattern.Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial ben-efits for patients aged 65-75 years,showing no significant difference compared to younger patients.This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy.For individuals older than 75 years,the survival effect was not evident,though.Immune-related adverse events(irAEs)with ICIs alone were similar in incidence across age catego-ries.Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone,and patients ≥75 years of age were more likely to experience higher-grade irAEs.Besides the fact that immunosenescence in older patients influ-ences the immune milieu in a multifaceted manner,which in turn impacts the effectiveness of immunotherapy,the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status(ECOG PS)score,among other factors.For certain individuals aged ≥75 years or in poor physical health,immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option.However,there are fewer related studies,so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment op-tions.To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new thera-peutic perspectives in combination with their characteristics,this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors in these patients.
6.A Comparative Study of the Efficacy and Safety of Immune Monotherapy versus Immunotheray Combined with Chemotherapy in Elderly Patients Aged 75 Years and Above with Advanced Non-small Cell Lung Cancer
MAO YUNYE ; WANG AN ; SHENG SHU ; JIA YANGYANG ; GE XIANGWEI ; ZHAI JINZHAO ; WANG JINLIANG
Chinese Journal of Lung Cancer 2024;27(9):665-673
Background and objective The malignant tumor that has the highest global morbidity and death rate is lung cancer,which primarily affects the elderly.The therapy landscape for non-small cell lung cancer(NSCLC)has trans-formed with the introduction of immune checkpoint inhibitors(ICIs).The purpose of this study was to compare the safety and efficacy of immune monotherapy and immunotheray combined with chemotherapy in patients with advanced NSCLC aged 75 years and above.Methods This study retrospectively analyzed 111 patients with advanced NSCLC who were at least 75 years old and received treatment at the First or Fifth Medical Centers of the People's Liberation Army General Hospital from January 2018 to October 2022.These patients underwent first-line or second-line treatment,with 70 receiving immunotherapy combined with chemotherapy and 41 receiving immunotherapy alone.Propensity score matching(PSM)was used to match the baseline characteristics of the patients,including age,Eastern Cooperative Oncology Group performance status(ECOG PS)score,and the number of treatment lines.The study endpoints included objective response rate(ORR),progression-free survival(PFS),overall survival(OS),and safety assessment.Results The median OS for the immunotherapy combined with chemother-apy group was 27.87 months,and the median PFS was 11.50 months.The median OS for the immune monotherapy group was 34.93 months,and the median PFS was 17.00 months.There were no significant differences in OS(P=0.722)and PFS(P=0.474)between the two groups,but a significant difference was observed in ORR(P=0.025).After PSM matching,each group comprised 27 patients.The median OS for the immunotherapy combined with chemotherapy group was 17.70 months,the median PFS was 8.97 months.The median OS for the immune monotherapy group was 17.87 months,and the median PFS was 11.53 months.No significant differences were observed in OS(P=0.635),PFS(P=0.878)and ORR(P=0.097).In terms of safety,the overall inci-dence of adverse events(AEs)before matching was 62.86% in the immunotherapy combined with chemotherapy group,which was higher than 41.46% in the immune monotherapy group(P=0.029),while there was no difference in the incidence of AEs of grade 3 or above between the two groups(P=0.221).After matching,AEs occurred in 17(62.96% )patients in the immunotherapy combined with chemotherapy group and 13(48.15% )in the immune monotherapy group.There were no significant differences in the overall incidence of AEs(P=0.273)or the incidence of grade 3 or above(P=0.299)between the two groups.Conclusion Im-munotherapy combined with chemotherapy does not significantly improve OS or PFS in patients with NSCLC aged 75 years and above when compared to immunotherapy alone,and this conclusion was further validated by the analysis after PSM.The safety assessment suggests that before matching,the incidence of AEs of any grade in the immunotherapy combined with chemotherapy group was higher.Still,the two groups had no difference in the incidence of AEs of grade 3 or above.Following matching,the tol-erability of the treatment was similar in both groups.According to the safety assessment,the unique circumstances and course of treatment for geriatric patients with advanced NSCLC should be considered.
7.Glutathione peroxidase 3-modified mesenchymal stem cells attenuate radiation-induced lung injury by reducing oxidative damage
Rui ZHAI ; Fumin TAI ; Kexin DING ; Changhui GE ; Xiaofei ZHENG ; Hanjiang FU
Military Medical Sciences 2024;48(7):487-494
Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.
8.Research progress in estrogen as an adjunctive therapy for schizophrenia.
Yanyu GE ; Shungeng ZHANG ; Xinbin GE ; Ranran LI ; Jinguo ZHAI ; Yan GAO
Journal of Central South University(Medical Sciences) 2024;49(11):1849-1860
Schizophrenia is a chronic psychiatric disorder with complex etiology and diverse clinical manifestations, whose pathogenesis and triggering factors remain incompletely understood. Numerous studies have demonstrated significant gender differences in the age of onset, clinical presentation, disease progression, treatment efficacy, and prognosis among patients with schizophrenia. These differences are largely attributed to variations in sex hormone levels, with estrogen emerging as a key focus of research. Some studies suggest that adjunctive estrogen therapy during schizophrenia treatment not only alleviates symptoms but also reduces the required dosage of antipsychotic medications. A systematic review of research on estrogen as an adjunctive treatment for schizophrenia may provide new perspectives and references for future therapeutic strategies.
Humans
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Schizophrenia/drug therapy*
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Estrogens/therapeutic use*
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Antipsychotic Agents/administration & dosage*
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Male
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Female
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Sex Characteristics
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Clinical Trials as Topic
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Estrogen Replacement Therapy
9.Characteristics of Syndrome Differentiation and Immune Imbalance in Children with Atopic Dermatitis
Panpan ZHAI ; Yanjie HUANG ; Xiaofeng MEI ; Jiajia LI ; Xiumin LI ; Xia ZHANG ; Wensheng ZHAI ; Xianqing REN ; Ying DING ; Chenhong XUE ; Ge QIAN ; Mingsan MIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(6):2168-2173
Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.
10.Effect of injury degree of osteoporotic vertebral compression fracture on bone cement cortical leakage after percutaneous kyphoplasty.
Xubing HUANG ; Wei JIAO ; Yunlei ZHAI ; Wei ZHANG ; Haitao LU ; Jishi JIANG ; Yu GE ; Haiyang YU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(4):452-456
OBJECTIVE:
To analyze the correlation between bone cement cortical leakage and injury degree of osteoporotic vertebral compression fracture (OVCF) after percutaneous kyphoplasty (PKP), and to provide guidance for reducing clinical complications.
METHODS:
A clinical data of 125 patients with OVCF who received PKP between November 2019 and December 2021 and met the selection criteria was selected and analyzed. There were 20 males and 105 females. The median age was 72 years (range, 55-96 years). There were 108 single-segment fractures, 16 two-segment fractures, and 1 three-segment fracture. The disease duration ranged from 1 to 20 days (mean, 7.2 days). The amount of bone cement injected during operation was 2.5-8.0 mL, with an average of 6.04 mL. Based on the preoperative CT images, the standard S/H ratio of the injured vertebra was measured (S: the standard maximum rectangular area of the cross-section of the injured vertebral body, H: the standard minimum height of the sagittal position of the injured vertebral body). Based on postoperative X-ray films and CT images, the occurrence of bone cement leakage after operation and the cortical rupture at the cortical leakage site before operation were recorded. The correlation between the standard S/H ratio of the injured vertebra and the number of cortical leakage was analyzed.
RESULTS:
Vascular leakage occurred in 67 patients at 123 sites of injured vertebrae, and cortical leakage in 97 patients at 299 sites. Preoperative CT image analysis showed that there were 287 sites (95.99%, 287/299) of cortical leakage had cortical rupture before operation. Thirteen patients were excluded because of vertebral compression of adjacent vertebrae. The standard S/H ratio of 112 injured vertebrae was 1.12-3.17 (mean, 1.67), of which 87 cases (268 sites) had cortical leakage. The Spearman correlation analysis showed a positive correlation between the number of cortical leakage of injured vertebra and the standard S/H ratio of injured vertebra ( r=0.493, P<0.001).
CONCLUSION
The incidence of cortical leakage of bone cement after PKP in OVCF patients is high, and cortical rupture is the basis of cortical leakage. The more severe the vertebral injury, the greater the probability of cortical leakage.
Male
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Female
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Humans
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Aged
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Kyphoplasty/methods*
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Bone Cements
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Fractures, Compression/surgery*
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Spinal Fractures/surgery*
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Retrospective Studies
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Osteoporotic Fractures/etiology*
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Treatment Outcome
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Vertebroplasty/methods*

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