1.Evaluation of colistin sulfate administration regimen based on PK/PD theory and Monte Carlo simulation
Yingchao MA ; Xia WU ; Yongjing WANG ; Jianjun GU ; Xiuling YANG
China Pharmacy 2025;36(4):459-463
OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics (PK)/pharmacodynamics (PD) theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration (MIC) data of colistin sulfate against Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC (fAUC0-24 h/MIC) ≥15 as the target value, the probabilities of target attainment (PTA) of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC; and the expected population PTA, specifically the cumulative fraction of response (CFR), for each regimen within a specific bacterial population was further calculated, to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL, PTA of all colistin sulfate regimens (500 000 IU, q12 h; 500 000 IU, q8 h; 750 000 IU, q12 h; 750 000 IU, q8 h; 1 000 000 IU, q12 h) were all more than 90%. When bacterial MIC=1 µg/mL, PTA for regimen (750 000 IU, q8 h) against A. baumannii, K. pneumoniae, P. aeruginosa, E. coli and E. cloacae, and for regimen (1 000 000 IU, q12 h) against the other four bacterial species (excluding P. aeruginosa) remained above 90%. When bacterial MIC≥2 µg/mL, PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli, the CFR of only colistin sulfate regimen (500 000 IU, q12 h) was less than 90%; for K. pneumoniae, the CFR of only colistin sulfate regimen (750 000 IU, q8 h and 1 000 000 IU, q12 h) was greater than 90%; for the other three bacteria, CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL, colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL, an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.
2.Computational Modeling of the Prefrontal-Cingulate Cortex to Investigate the Role of Coupling Relationships for Balancing Emotion and Cognition.
Jinzhao WEI ; Licong LI ; Jiayi ZHANG ; Erdong SHI ; Jianli YANG ; Xiuling LIU
Neuroscience Bulletin 2025;41(1):33-45
Within the prefrontal-cingulate cortex, abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions, contributing to the development of mental disorders such as depression. Despite this understanding, the neural circuit mechanisms underlying this phenomenon remain elusive. In this study, we present a biophysical computational model encompassing three crucial regions, including the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and ventromedial prefrontal cortex. The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes. The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks. Furthermore, our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex, and network functionality was restored through intervention in the dorsolateral prefrontal cortex. This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.
Prefrontal Cortex/physiology*
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Humans
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Emotions/physiology*
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Cognition/physiology*
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Gyrus Cinguli/physiology*
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Computer Simulation
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Models, Neurological
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Neural Pathways/physiology*
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Nerve Net/physiology*
3.Application of multidisciplinary family empowerment mode in home care for patients after percutaneous endoscopic gastrostomy
Yu LI ; Zhicheng HUANG ; Haili FANG ; Jing YANG ; Caixia MOU ; Lijuan WANG ; Yanjiang LIU ; Xiuling ZHOU
Journal of Interventional Radiology 2024;33(11):1234-1238
Objective To discuss the effect of multidisciplinary family empowerment mode in home care for patients after receiving percutaneous endoscopic gastrostomy(PEG).Methods A total of 86 patients,who received initial PEG at the Jilin Provincial Cancer Hospital of China from January 2021 to July 2023,were selected for this study.The patients were randomly divided into observation group.The patients of the control group received routine nursing guidance for gastrostomy,while the patients of the observation group received multidisciplinary family empowerment nursing mode.The self-care ability[using self-care ability scale of the elderly(SASE)score],health behavior ability[using self-rating scale of health behavior ability(SRAHP)score],incidence of complications,and healing time of complications were compared between the two groups.Results In the observation group the SASE[(129.48±5.48)points vs.(73.05±12.04)points]and the SRAHP[(80.14±1.00)points vs.(70.25±7.92)points]were significantly higher than those in the control group(all P<0.05),the incidence of complications was lower than that in the control group,and the healing time of complications was shorter than that in the control group.Conclusion The implementation of multidisciplinary family empowerment nursing mode can improve the self-care ability and health behavior ability of patients after receiving PEG,reduce postoperative complications,as well as shorten the healing time of complications,therefore,this nursing mode is suitable for home patients after receiving PEG.
4.Effects of lung rehabilitation based on Spiro-tiger training apparatus on respiratory mechanics and airway remodeling in stable COPD patients
Jie DING ; Wenhai XIANG ; Qixing WANG ; Xiuling GONG ; Yang YANG ; Guili WANG ; Wei XIAO
Chinese Journal of Medical Physics 2023;40(12):1558-1563
Objective To explore the effects of lung rehabilitation using Spiro-tiger training apparatus on the respiratory mechanics and airway remodeling in patients with chronic obstructive pulmonary disease(COPD)in stable stage.Methods Ninety-three stable COPD patients admitted to Nanxiang Branch of Shanghai Ruijin Hospital were randomly divided into control group(46 cases)and observation group(47 cases).Control group was treated with the training for pursed lips breathing and abdominal breathing,and observation group was trained with Spiro-tiger training apparatus in addition to the treatment given to control group.Both groups were intervened continuously for 9 weeks.The two groups were compared in terms of respiratory mechanics(respiratory frequency,tidal volume,minute ventilation,and peak respiratory pressure),airway remodeling[matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),and transforming growth factor-β1(TGF-β1)],and lung function[forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),and FEV1/FVC],blood gas analysis indexes[arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2)],6-minute walking distance(6MWD)and health status[Borg scale and St.George's respiratory questionnaire(SGRQ)].The patients were followed up for 6 months,and the incidence of acute exacerbation of COPD was recorded.Results After 9 weeks of intervention,compared with control group,observation group had lower peak respiratory frequency and respiratory pressure,and higher tidal volume(P<0.05).There was no significant difference in minute ventilation between two groups(P>0.05).The levels of MMP-9,VEGF,TGF-β1 and PaCO2 were lower,and FVC,FEV1,FEV1/FVC and PaO2 were higher in observation group than in control group(P<0.05).Observation group had longer 6MWD,and lower Borg score and SGRQ score as compared with control group(P<0.05).After 6-month follow-up,the incidence of COPD acute exacerbation in observation group was lower than that in control group(4.26%vs19.57%,P<0.05).Conclusion Lung rehabilitation using Spiro-tiger training apparatus can effectively improve respiratory mechanics,lung function,blood gas analysis indexes and health status in stable COPD patients,alleviate airway remodeling,and avoid acute exacerbation of COPD.
5.Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.
Xinyan WANG ; Xiuling XU ; Ting ZHANG ; Yang JIN ; Sheng XU ; Lifeng CHEN ; Yucheng LAI ; Ling ZHANG ; Ruolang PAN ; Yan YU
Journal of Zhejiang University. Science. B 2023;24(3):262-268
Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.
Female
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Humans
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Proto-Oncogene Proteins c-akt
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Phosphatidylinositol 3-Kinases
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Endometrial Neoplasms
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Estrogens
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Breast Neoplasms
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DNA Helicases
6.The key mechanism underlying resistance to anti-angiogenic therapy in liver cancer: vessel co-option
Dan YANG ; Xiangming DING ; Dongxiao LI ; Shumin DANG ; Yujin PAN ; Xiuling LI ; Deyu LI
Chinese Journal of Digestive Surgery 2023;22(S1):112-116
The growth of solid tumors rely on angiogenesis to establish blood supply, and inducing neovascularization is a necessary condition for the growth of solid tumors. Anti-angiogenic therapies have been developed for tumors based on this theory. Although liver cancer is considered as a highly angiogenic tumor, the effectiveness of these drugs in anti-angiogenic therapies on liver cancer has not met expectations. In recent years, vessel co-option, as a long-standing but overlooked mechanism of vascularization of non-angiogenic tumors, has gradually attracted attention. Tumor tissue can promote its own growth by "hijacking" existing blood vessels in the para-carcinoma tissue instead of inducing angiogenesis, known as vessel co-option or vascular hijacking. Vessel co-option has been observed in a variety of tumors, both primary and metastatic, and is believed to be a key mechanism of anti-angiogenic resistance. The authors systematically examine the evidence, clinical prognosis, and molecular mechanisms of vessel co-option in liver cancer, and discuss its potential role in anti-angiogenic therapeutic resistance and alternative anti-tumor strategies for liver cancer.
7.Clinical significance and prognostic value of fibrinogen in the treatment of locally advanced head and neck squamous cell carcinoma treated with induction chemotherapy combined with radiotherapy
Xiaoyan WANG ; Yuanyuan LI ; Yang YANG ; Feng JIN ; Weili WU ; Jinhua LONG ; Xiuling LUO ; Xiuyun GONG ; Xiaoxiao CHEN
Chinese Journal of Radiological Medicine and Protection 2022;42(12):935-942
Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.
8.Study of hospitalization risk indicators for intensive care unit patients evaluated by intelligent calculation method
Xiaoming HOU ; Xiaoyu CHEN ; Wanjie YANG ; Bo KANG ; Xiangfei MENG ; Senle ZHANG ; Qingguo FENG ; Xiaozhi LIU ; Haiyan ZHANG ; Junfei WANG ; Ying SONG ; Xiuling CHENG ; Hongyun TENG
Chinese Critical Care Medicine 2022;34(12):1315-1319
Objective:To explore the characteristics of the changes in risk score for intensive care unit (ICU) patients during hospitalization by the intelligent calculation method, and to provide evidence for the risk prevention.Methods:In this retrospective study, ICU patients of the Fifth Central Hospital in Tianjin from November 3, 2021 to March 28, 2022 were enrolled and divided into ≥ 14 days group, 10-13 days group, 7-9 days group, and 3-6 days group according to the ICU length of stay. Risk scores assessed by the intelligent calculation method of the ICU patients were collected, including nutritional risk screening 2002 (NRS 2002), Caprini score and Padua score. NRS 2002 score for all patients, Caprini score for surgical patients and Padua score for internal medicine patients were selected. Trends in change of each score were compared between patients admitted to ICU 1, 3, 7 (if necessary), 10 (if necessary), and 14 days (if necessary).Results:A total of 138 patients were involved, including 79 males and 59 females, with an average age of (61.71±18.86) years and an average hospital stay of [6.00 (4.00, 9.25)] days. ① in the group with ICU length of stay ≥ 14 days (21 cases): there was no significant change in the NRS 2002 scores of the patients within 10 days, but the NRS 2002 score was significantly decreased in 14 days as compared with 1 day [3.00 (2.50, 3.50) vs. 4.00 (3.00, 5.00), P < 0.05]; both Caprini and Padua score were increased with prolonged hospital stay and compared with 1 day, the scores at the other time points were significantly increased, especially at 14 days [Caprini score: 5.00 (3.25, 7.00) vs. 2.50 (1.25, 5.50), Padua score: 6.00 (6.00, 7.00) vs. 3.00 (1.00, 3.00), both P < 0.05].② in the group with ICU length of stay from 10-13 days (15 cases): with the prolonged hospital stay, there was no significant change in NRS 2002 score, but both Caprini and Padua score were increased at 3, 7, 10 days, especially at 10 days [Caprini score: 3.00 (2.00, 4.75) vs. 2.00 (0.25, 2.75), Padua score: 5.00 (3.50, 6.00) vs. 2.00 (0.50, 4.00), both P < 0.05].③ in the group with ICU length of stay from 7-9 days (23 cases): compared with 1 day, the NRS 2002 score at 3 days and7 days were decreased, but the Caprini and Padua score were increased, especially at 7 days [NRS 2002 score: 2.00 (1.00, 4.00) vs. 2.00 (2.00, 4.00), Caprini score: 3.00 (2.00, 5.50) vs. 2.00 (0.25, 3.00), Padua score: 5.00 (4.00, 6.00) vs. 2.00 (0, 2.00), all P < 0.05]. ④ in the group with ICU length of stay from 3-6 days (79 cases): compared with 1 day, the NRS 2002 score at 3 days was decreased [NRS 2002 score: 2.00 (1.00, 3.00) vs. 2.00 (1.00, 3.00), P < 0.05], Caprini and Padua score were significantly increased [Caprini score: 3.00 (2.00, 4.00) vs. 2.00 (1.00, 3.00), Padua score: 5.00 (4.00, 5.00) vs. 2.00 (1.00, 3.00), both P < 0.05]. Conclusion:Based on dynamic assessment of intelligent calculation methods, the risk of thrombosis in ICU patients increased with hospital length of stay, and the nutritional risk was generally flat or reducing in different hospitalization periods.
9.Control study of the intelligent calculation method and the traditional calculation method in risk assessments of hospitalization
Wanjie YANG ; Xiaoming HOU ; Xiangfei MENG ; Bo KANG ; Xiaozhi LIU ; Haiyan ZHANG ; Junfei WANG ; Ying SONG ; Senle ZHANG ; Xiuling CHENG
Chinese Critical Care Medicine 2022;34(5):533-537
Objective:To explore the accuracy of intelligent calculation (IC) method for risk assessment of hospitalization for patients, aiming to build a more advantageous risk assessment system.Methods:The "Search Engine" program was developed based on hospital information system (HIS) of the Fifth Center Hospital in Tianjin, which automatically captured patient information and generated nutritional risk screening 2002 (NRS 2002) score, Caprini thrombosis risk assessment model and Padua thrombosis risk assessment model for venous thromboembolism (VTE), the CHA 2DS 2-VASc for predicting stroke risk stratification in atrial fibrillation and the HAS-BLED for predicting bleeding risk in anticoagulated patients with atrial fibrillation. A randomized controlled trial was conducted. According to the applicable conditions of each risk assessment, 100 risk scores from "Search Engine" program belonged to each risk assessment were randomly selected, defined as the IC group. Manual scoring with the data of the same case at the same time, defined as the traditional calculation (TC) group, compared the consistency of the scores and the difference in time-consuming between the two groups. Results:The Bland-Altman plots showed that the 95% limits of agreement (95% LoA) of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score was -0.46 to 0.41, -0.49 to 0.52, -0.50 to 0.41, -0.67 to 0.60, -0.44 to 0.43, respectively, all P > 0.05. In this study, the Bland-Altman plot showed that 95%, 96%, 97%, 97%, 95% plots fell within the 95% LoA in NRS 2002 score, Caprini score, Padua score, wwCHA 2DS 2-VASc score and HAS-BLED score by the two methods, respectively. The all plots of 95% LoA were within the clinically acceptable range (-0.5 to 0.5 scores). The time-consuming of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score in IC group were significantly shorter than those in TC group [0.72 (0.71, 0.73) seconds vs. 361.02 (322.41, 361.02) seconds, 0.72 (0.72, 0.73) seconds vs. 196.68 (179.99, 291.20) seconds, 0.72 (0.72, 0.73) seconds vs. 105.75 (92.32, 114.70) seconds, 0.72 (0.71, 0.72) seconds vs. 72.66 (56.24, 84.20) seconds, 0.72 (0.71, 0.72) seconds vs. 51.30 (38.88, 57.15) seconds, respectively, all P < 0.001]. Conclusion:For the above five risk assessments, the TC method and IC method has good consistency in scores, and the IC method is faster, which has good application prospect for clinical application.
10.Atypical magnetic resonance imaging findings, misdiagnosis analysis and functional imaging value of primary central nervous system lymphoma
Lei GENG ; Yi SUN ; Rui WANG ; Jinxin WAN ; Fumeng YANG ; Xiuling WANG ; Kai XU
Journal of Chinese Physician 2022;24(11):1649-1654,1660
Objective:To observe and analyze the atypical magnetic resonance imaging (MRI) findings and misdiagnosis reasons of primary central nervous system lymphoma (PCNSL), and to explore the value of conventional MRI signs combined with minimum apparent diffusion coefficient value (ADCmin) and imaging features of magnetic resonance spectroscopy (MRS) in the diagnosis and differentiation of atypical PCNSL.Methods:The clinical and imaging data of 15 patients with atypical PCNSL confirmed by clinical and pathological findings from Lianyungang Second People′s Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2020 was collected. All cases were examined by plain MRI, enhanced and diffusion weighted imaging (DWI), and 3 cases were examined by MRS. The conventional MRI features, DWI signal features and MRS imaging features of 15 cases of atypical PCNSL were observed and analyzed, and the MRI findings of atypical PCNSL and the causes of misdiagnosis were summarized and analyzed. The ADCmin of tumor parenchyma, the mean ADC values of proximal peritumor, distal peritumor and contralateral white matter were detected and compared to explore the variation rules of ADC values in different regions.Results:Of the 15 cases of PCNSL, 14 cases were single and 1 case was multiple, with a total of 21 lesions. (1) Single lesions in rare sites: 4 cases in the superficial part of the brain, 1 case in the bridge arm, 1 case in the cerebellar hemisphere, 1 case in the suprasellar saddle, and 1 case in the third ventricle. (2) Atypical MRI findings: cystic degeneration or necrosis in 5 lesions (5/21), accompanied by hemorrhage in 1 lesion (1/21); There were 3 isosensitive lesions on DWI, and isosensitive lesions on ADC false color images. There were 5 ring enhancement lesions and 3 sheet enhancement lesions. (3) Multi-center growth pattern: 1 case with a total of 7 lesions, located in the right thalamus, basal ganglia and corona radiata, showing multiple nodules and ring enhancement. 1H-MRS examination showed that choline (Cho) peak increased, creatine (Cr) peak decreased, N-acetyl aspartate (NAA) peak decreased, and obvious Lip peak appeared in all the 3 cases with single lesions. 2 cases showed high Lip peak as the first peak. The ADCmin values of tumor parenchyma, proximal peritumor, distal peritumor and contralateral white matter showed a parabola pattern of first rise and then decline, as follows: (0.54±0.06)×10 -3 mm 2/s, (1.55±0.10)×10 -3 mm 2/s, (1.45±0.09)×10 -3 mm 2/s, (0.85±0.03)×10 -3 mm 2/s, overall difference was statistically significant ( F=630.570, P<0.001). The pairwise comparison was statistically significant (all P<0.05). Conclusions:Atypical PCNSL is easy to be misdiagnosed. Conventional MRI feature analysis combined with DWI and MRS imaging features and comparison of ADC values in different tumor areas are helpful for the diagnosis and differentiation of PCNSL and are expected to improve diagnostic accuracy.

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