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
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
2.Application of subcutaneous tunneling in drainage of chronic subdural hematoma
Junjun LI ; Luoning SHI ; Yi XIAO ; Mei WANG ; Yalin YANG ; Changwang DU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):280-284
Objective To explore the clinical value of subcutaneous tunneling in the management of chronic subdural hematoma.Methods A retrospective analysis was conducted on 279 cases of unilateral chronic subdural hematoma treated at the Neurosurgery Department of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019.The patients were randomly assigned to subcutaneous tunnel group(n=164)and control group(n=115)through double-blind randomization.In the subcutaneous tunnel group,the intraoperative drainage tube was extracted through a subcutaneous tunnel,while in the control group,the drainage tube was removed directly from the incision.We analyzed the hematoma clearance rate,complications,and hematoma recurrence rate after 6 months.Results There was no statistical significance in age,sex,comorbidities,hematoma side or hematoma volume between the two groups(P>0.05).Subcutaneous tunnel group and control group did not significantly differ in operation time[(27.68±4.1)min vs.(27.50±4.02)min],hospital stay[(7.39±1.04)d vs.(7.42±1.04)d],tube removal time[(24.30±4.82)h vs.25.37±5.02)h],or other clinical features(all P>0.05).The clearance rate of hematoma was significantly higher in subcutaneous tunnel group than in control group(97.6%vs.95.7%,Z=-3.897,P<0.001).There were 6 cases(3.7%)of hematoma recurrence in the subcutaneous tunnel group and 11 cases(9.6%)in the control group.The subcutaneous tunnel group had significantly lower recurrence of hematoma than the control group(x2=4.122,P=0.042).Conclusion Subcutaneous tunneling for drainage in the treatment of chronic subdural hematoma can increase the hematoma clearance rate and reduce the rates of complications and recurrence.This technique is simple and worthy of broad clinical application.
3.Consistency analysis of IHC and PCR-CE in the detection of microsatellite insta-bility in 735 tumor cases
Ying GUO ; Yalin CHENG ; Xiangyu ZHAO ; Xinxin YANG ; Hongxue MENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(8):1050-1056
Purpose To investigate the consistency and reliability of immunohistochemistry(IHC)staining and polymerase chain reaction-capillary electrophoresis(PCR-CE)in the detection of microsatellite instability.Methods The clinical data of 735 patients with solid tumors who underwent biopsy or surgical resection were collected,and the microsatellite status of tissue samples was detected by IHC and PCR-CE.Results Among the 344 cases of colorectal cancer(CRC),IHC results showed that 290 cases(84.3%)had proficient mismatch repair(pMMR),and 54 cases(15.7%)had deficient mismatch repair(dMMR).The results of PCR-CE showed that 53 patients(15.4%)had high microsatellite instability(MSI-H),and 291 patients(84.6%)had microsatellite stable(MSS).The consistency analysis of IHC and PCR-CE results showed that the Kappa value was 0.923(P<0.001).Among the 168 cases of en-dometrial cancer(EC),IHC results showed that 42 cases(25.0%)had dMMR and 126 cases(75.0%)had pMMR;The results of PCR-CE showed that 39 cases(23.2%)had MSI-H and 129 cases(76.8%)had MSS.The consisten-cy analysis of the two methods showed that the Kappa value was 0.854(P<0.001).Among the 165 cases of gastric cancer,IHC results showed that 22(13.3%)had dMMR and 143(86.7%)had pMMR;The results of PCR-CE showed that 22 cases(13.3%)had MSI-H and 143 cases(86.7%)had MSS/low microsatellite instability(MSI-L).The consistency analysis of IHC and PCR-CE results showed that the Kappa value was 0.843(P<0.001).Among the 58 cases of head and neck squamous cell carcinoma(HNSCC),IHC results showed that 3 cases(5.2%)had dMMR and 55 cases(94.8%)had pMMR;The results of PCR-CE showed that 3 cases(5.2%)had MSI-H and 55 cases(94.8%)had MSS.The consistency analysis of the two methods showed that the Kappa value was 1.000(P<0.001).Conclusion IHC and PCR-CE have high consistency and reliability in detecting MSI status in patients with CRC,EC,gastric cancer and HNSCC,and their combined application is helpful to improve the accuracy of MSI detec-tion in patients with solid tumors.
4.Effect of pneumatic and electric hand training system with multiple sensory stimulation modalities combined with low-frequency repetitive transcranial magnetic stimulation on hand movement and tactile pressure sensation in patients with stroke
Pengcheng LIU ; Mengjian QU ; Liping LONG ; Yalin WANG ; Mingzhu YANG ; Peiyong LIU ; Jun ZHOU ; Jing LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(4):458-465
Objective To explore the effect of the pneumatic and electric hand training system with multiple sensory stimulation mo-dalities combined with low-frequency repetitive transcranial magnetic stimulation on hand movement and tactile pressure sensation in patients with stroke.Methods From May,2023 to October,2024,62 stroke patients from the First Affiliated Hospital of University of South China were randomly divided into control group(n=31)and experimental group(n=31).Both groups received conventional rehabilitation,and 1 Hz low-frequency repetitive transcranial magnetic stimulation in the primary cerebral motor cortex on the unaffected side,while the experimental group received the pneumatic and electric hand training system with multiple sensory stimulation modalities in addition,for four weeks.They were as-sessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),Motor Assessment Scale(MAS),Semmes Weinstein Monofilament Test(SWMT)and modified Barthel index(MBI)before and after treatment.Results One case dropped out in control group and one in the experimental group.After treatment,the scores of FMA-UE,MAS,SWMT and MBI increased in both groups(|t|>5.464,P<0.001),expect the score of SWMT in the control group(P>0.05),and all scores were better in the experimental group than in the control group(|t|>2.195,P<0.05).Conclusion The pneumatic and electric hand training system with multiple sensory stimulation modalities combined with low-frequency repetitive transcranial magnetic stimulation can improve the motor and tactile pressure func-tion of stroke patients,and improve their activity of daily living.
5.Advances in the application of artificial intelligence in the pathological practice of head and neck squamous cell carcinoma
Yalin CHENG ; Ying GUO ; Xinxin YANG ; Hongxue MENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(4):498-503
Head and neck squamous cell carcinoma(HNSCC)is the most common pathological subtype of head and neck malignancies.The majority of patients are diagnosed at an advanced stage,losing the opportunity for curative surgery,and overall prognosis remains poor.With its exceptional capabilities in image analysis and powerful data pro-cessing,artificial intelligence(AI)has the potential to become a valuable tool in precision pathology,offering new op-portunities to improve the diagnosis and treatment of head and neck cancer.This article provides a systematic review of the current research status on AI-assisted pathological image analysis in the diagnosis,treatment strategy selection,and prognosis prediction of HNSCC,while also discussing future research directions.
6.Application of subcutaneous tunneling in drainage of chronic subdural hematoma
Junjun LI ; Luoning SHI ; Yi XIAO ; Mei WANG ; Yalin YANG ; Changwang DU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):280-284
Objective To explore the clinical value of subcutaneous tunneling in the management of chronic subdural hematoma.Methods A retrospective analysis was conducted on 279 cases of unilateral chronic subdural hematoma treated at the Neurosurgery Department of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019.The patients were randomly assigned to subcutaneous tunnel group(n=164)and control group(n=115)through double-blind randomization.In the subcutaneous tunnel group,the intraoperative drainage tube was extracted through a subcutaneous tunnel,while in the control group,the drainage tube was removed directly from the incision.We analyzed the hematoma clearance rate,complications,and hematoma recurrence rate after 6 months.Results There was no statistical significance in age,sex,comorbidities,hematoma side or hematoma volume between the two groups(P>0.05).Subcutaneous tunnel group and control group did not significantly differ in operation time[(27.68±4.1)min vs.(27.50±4.02)min],hospital stay[(7.39±1.04)d vs.(7.42±1.04)d],tube removal time[(24.30±4.82)h vs.25.37±5.02)h],or other clinical features(all P>0.05).The clearance rate of hematoma was significantly higher in subcutaneous tunnel group than in control group(97.6%vs.95.7%,Z=-3.897,P<0.001).There were 6 cases(3.7%)of hematoma recurrence in the subcutaneous tunnel group and 11 cases(9.6%)in the control group.The subcutaneous tunnel group had significantly lower recurrence of hematoma than the control group(x2=4.122,P=0.042).Conclusion Subcutaneous tunneling for drainage in the treatment of chronic subdural hematoma can increase the hematoma clearance rate and reduce the rates of complications and recurrence.This technique is simple and worthy of broad clinical application.
7.Advances in the application of artificial intelligence in the pathological practice of head and neck squamous cell carcinoma
Yalin CHENG ; Ying GUO ; Xinxin YANG ; Hongxue MENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(4):498-503
Head and neck squamous cell carcinoma(HNSCC)is the most common pathological subtype of head and neck malignancies.The majority of patients are diagnosed at an advanced stage,losing the opportunity for curative surgery,and overall prognosis remains poor.With its exceptional capabilities in image analysis and powerful data pro-cessing,artificial intelligence(AI)has the potential to become a valuable tool in precision pathology,offering new op-portunities to improve the diagnosis and treatment of head and neck cancer.This article provides a systematic review of the current research status on AI-assisted pathological image analysis in the diagnosis,treatment strategy selection,and prognosis prediction of HNSCC,while also discussing future research directions.
8.Consistency analysis of IHC and PCR-CE in the detection of microsatellite insta-bility in 735 tumor cases
Ying GUO ; Yalin CHENG ; Xiangyu ZHAO ; Xinxin YANG ; Hongxue MENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(8):1050-1056
Purpose To investigate the consistency and reliability of immunohistochemistry(IHC)staining and polymerase chain reaction-capillary electrophoresis(PCR-CE)in the detection of microsatellite instability.Methods The clinical data of 735 patients with solid tumors who underwent biopsy or surgical resection were collected,and the microsatellite status of tissue samples was detected by IHC and PCR-CE.Results Among the 344 cases of colorectal cancer(CRC),IHC results showed that 290 cases(84.3%)had proficient mismatch repair(pMMR),and 54 cases(15.7%)had deficient mismatch repair(dMMR).The results of PCR-CE showed that 53 patients(15.4%)had high microsatellite instability(MSI-H),and 291 patients(84.6%)had microsatellite stable(MSS).The consistency analysis of IHC and PCR-CE results showed that the Kappa value was 0.923(P<0.001).Among the 168 cases of en-dometrial cancer(EC),IHC results showed that 42 cases(25.0%)had dMMR and 126 cases(75.0%)had pMMR;The results of PCR-CE showed that 39 cases(23.2%)had MSI-H and 129 cases(76.8%)had MSS.The consisten-cy analysis of the two methods showed that the Kappa value was 0.854(P<0.001).Among the 165 cases of gastric cancer,IHC results showed that 22(13.3%)had dMMR and 143(86.7%)had pMMR;The results of PCR-CE showed that 22 cases(13.3%)had MSI-H and 143 cases(86.7%)had MSS/low microsatellite instability(MSI-L).The consistency analysis of IHC and PCR-CE results showed that the Kappa value was 0.843(P<0.001).Among the 58 cases of head and neck squamous cell carcinoma(HNSCC),IHC results showed that 3 cases(5.2%)had dMMR and 55 cases(94.8%)had pMMR;The results of PCR-CE showed that 3 cases(5.2%)had MSI-H and 55 cases(94.8%)had MSS.The consistency analysis of the two methods showed that the Kappa value was 1.000(P<0.001).Conclusion IHC and PCR-CE have high consistency and reliability in detecting MSI status in patients with CRC,EC,gastric cancer and HNSCC,and their combined application is helpful to improve the accuracy of MSI detec-tion in patients with solid tumors.
9.Effect of pneumatic and electric hand training system with multiple sensory stimulation modalities combined with low-frequency repetitive transcranial magnetic stimulation on hand movement and tactile pressure sensation in patients with stroke
Pengcheng LIU ; Mengjian QU ; Liping LONG ; Yalin WANG ; Mingzhu YANG ; Peiyong LIU ; Jun ZHOU ; Jing LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(4):458-465
Objective To explore the effect of the pneumatic and electric hand training system with multiple sensory stimulation mo-dalities combined with low-frequency repetitive transcranial magnetic stimulation on hand movement and tactile pressure sensation in patients with stroke.Methods From May,2023 to October,2024,62 stroke patients from the First Affiliated Hospital of University of South China were randomly divided into control group(n=31)and experimental group(n=31).Both groups received conventional rehabilitation,and 1 Hz low-frequency repetitive transcranial magnetic stimulation in the primary cerebral motor cortex on the unaffected side,while the experimental group received the pneumatic and electric hand training system with multiple sensory stimulation modalities in addition,for four weeks.They were as-sessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),Motor Assessment Scale(MAS),Semmes Weinstein Monofilament Test(SWMT)and modified Barthel index(MBI)before and after treatment.Results One case dropped out in control group and one in the experimental group.After treatment,the scores of FMA-UE,MAS,SWMT and MBI increased in both groups(|t|>5.464,P<0.001),expect the score of SWMT in the control group(P>0.05),and all scores were better in the experimental group than in the control group(|t|>2.195,P<0.05).Conclusion The pneumatic and electric hand training system with multiple sensory stimulation modalities combined with low-frequency repetitive transcranial magnetic stimulation can improve the motor and tactile pressure func-tion of stroke patients,and improve their activity of daily living.
10.Phylogenetic analysis and pathogenesis study of a new deletion mutation causing inherited FⅩ deficiency
Dongyan FU ; Xiaomei LU ; Yalin YU ; Lidong ZHAO ; Lei WANG ; Jia YANG ; Jiawei ZHENG ; Duanyang WANG ; Linhua YANG ; Gang WANG
Chinese Journal of Hematology 2024;45(10):902-908
Objective:To analyze the F10 gene mutations in a Chinese pedigree affected with the deficiency of the hereditary coagulation factor X (FX), resulting from a new deletion mutation, and to study the associated molecular pathogenesis.Methods:Next generation sequencing (NGS) was performed to screen the genetic mutations in the proband which were then verified by Sanger sequencing. The FX activity (FX∶C) of probands and their family members was detected using the blood clotting method, and the mutation sites of the family members were analyzed using Sanger sequencing. The pathogenicity of the mutation site was predicted by using the online bioinformatics software, Mutation Taster. The SWISS-MODEL software was used for stimulating the three-dimensional models of the wild-type and mutant proteins for analyzing the influence of the mutation site on the structure and function of the proteins, and for analyzing the difference between the catalytic residues of the wild-type and the mutant proteins. The level of the F10 gene mRNA was quantitatively analyzed by qRT-PCR (quantitative reverse transcription polymerase chain reaction) method by constructing plasmids, transfecting human embryonic kidney 293T cells (HEK 293T), and analyzing the splicing of the mutated site by RT-PCR method. The levels of FⅩ∶Ag in cell lysates and cell culture media (both inside and outside the cells) were detected by the ELISA (enzyme linked immunosorbent assay) method.Results:A medium-grade factor X deficiency with a 36.42% FⅩ∶C ratio was detected in the proband by the coagulation method. NGS analysis demonstrated a heterozygous deletion mutation in exon 8:c.902_919del (p.Ala301_Glu306del) in the proband. Sanger sequencing analysis indicated that some members of the family (mother and grandfather) were also carriers of the corresponding deletion mutation. Online bioinformatics software predicted the pathogenic nature of the c.902_919del mutation, with a pathogenic score of 0.999. The 3D protein structure model analysis indicated that the c.902_919del mutation resulted in the disappearance of a segment of β-fold in the protein structure, thereby shortening the preceding segment of the β-fold and a subsequent loss of hydrogen bonds between adjacent amino acids with no significant difference in the side chain conformation of the key catalytic residues compared to the wild-type. mRNA splicing analysis indicated the absence of alternative splicing changes in the mutation, and qRT-PCR results indicated the absence of a statistically significant difference between the mRNA levels of F10 gene and wild-type mRNA in cells expressing c.902_919del mutant. The ELISA results indicated that there was no statistically significant difference in the FX∶Ag levels of the mutant cell culture medium and the lysate.Conclusions:In this pedigree, the heterozygous mutation in exon 8 of F10 gene (c.902_919del, p.Ala301_Glu306del) caused the hereditary factor Ⅹ deficiency.

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