1.Construction and Validation of A Nomogram Prediction Model of Febrile Seizure in Children
Cheng WANG ; Xingfu WEI ; Meitao ZHAO
Journal of Medical Research 2025;54(3):73-79
Objective To investigate the risk factors of febrile seizures(FS)in children,construct a visualization nomogram predic-tion model of FS and verify its effectiveness.Methods A retrospective analysis was conducted on the clinical data of 1320 children with fever admitted to the Gansu Provincial Maternity and Child-care Hospital(Gansu Provincial Central Hospital)from January 2019 to De-cember 2022.The samples were randomly divided into the training set and the validation set at a ratio of 7∶3.The clinical characteristics and laboratory examination of the two groups were compared.LASSO regression was used to select the risk factors for FS,and multivariate Logistic regression analysis was performed on the predictors,and construction a prediction mode,and the discrimination,calibration and clinical applicability of the model were evaluated.Results The results showed that age,low body weight,peak temperature,diurnal changes in onset,upper respiratory tract infection,serum sodium,serum calcium,white blood cell,procalcitonin were independent risk factors for FS in children.A predictive model was constructed and a nomogram was developed with these factors.The area under the re-ceiver operating characteristic(ROC)curve of the training set and the validation set were 0.870(95%CI:0.847-0.893)and 0.855(95%CI:0.817-0.894),respectively.The calibration plots and Hosmer-Lemeshow goodness-of-fit test showed its satisfactory cali-bration.The decision curve analysis(DCA)curve showed that the model provided a good net benefit with threshold probabilities when training set was>5%,while in the validation set it was>8%.Conclusion The risk prediction model based on LASSO-Logistic re-gression analysis can provide reference for early risk assessment of children with FS.
2.Correlation between p53 immunohistochemistry and TP53 mutations in gliomas
Xuefang LIN ; Chengcong HU ; Pingling WANG ; Xiaoli SU ; Jingjing WU ; Saifan ZENG ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Pathology 2025;54(4):375-380
Objective:To evaluate the accuracy of p53 immunohistochemistry for predicting the mutational status of TP53 in gliomas.Methods:A retrospective study was conducted on 242 diffuse gliomas diagnosed at the Department of Pathology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2022 to March 2023. All cases underwent next-generation sequencing (NGS) and p53 immunohistochemical staining. The best threshold in the percentage of p53 immunohistochemical expression was assessed as an alternative to testing for TP53 mutation.Results:Among the 242 diffuse gliomas (WHO grade 2-4), 94 cases had a TP53 mutation. The p53 immunohistochemistry results revealed a significantly increased probability of TP53 mutation when the p53 immunohistochemical positivity rate (based on strongly positive cell count) was ≥20% ( P<0.05). The sensitivity and specificity of p53 immunohistochemistry for predicting TP53 gene mutations were 75.6% and 90.4%, respectively. When p53 immunohistochemical stain was totally negative, the probability of TP53 mutation increased significantly, and the mutation ratio of TP53 gene was 6/17 in all negative cases. Conclusions:When the percentage of p53 positive cells (based on strongly positive cell count) in glioma is ≥20%, p53 immunohistochemistry can be used as a reliable alternative method for TP53 mutation detection. When p53 immunohistochemistry is completely negative, the mutation rate of TP53 gene is higher, and further gene sequencing is recommended to determine the mutation status.
3.Correlation between p53 immunohistochemistry and TP53 mutations in gliomas
Xuefang LIN ; Chengcong HU ; Pingling WANG ; Xiaoli SU ; Jingjing WU ; Saifan ZENG ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Pathology 2025;54(4):375-380
Objective:To evaluate the accuracy of p53 immunohistochemistry for predicting the mutational status of TP53 in gliomas.Methods:A retrospective study was conducted on 242 diffuse gliomas diagnosed at the Department of Pathology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2022 to March 2023. All cases underwent next-generation sequencing (NGS) and p53 immunohistochemical staining. The best threshold in the percentage of p53 immunohistochemical expression was assessed as an alternative to testing for TP53 mutation.Results:Among the 242 diffuse gliomas (WHO grade 2-4), 94 cases had a TP53 mutation. The p53 immunohistochemistry results revealed a significantly increased probability of TP53 mutation when the p53 immunohistochemical positivity rate (based on strongly positive cell count) was ≥20% ( P<0.05). The sensitivity and specificity of p53 immunohistochemistry for predicting TP53 gene mutations were 75.6% and 90.4%, respectively. When p53 immunohistochemical stain was totally negative, the probability of TP53 mutation increased significantly, and the mutation ratio of TP53 gene was 6/17 in all negative cases. Conclusions:When the percentage of p53 positive cells (based on strongly positive cell count) in glioma is ≥20%, p53 immunohistochemistry can be used as a reliable alternative method for TP53 mutation detection. When p53 immunohistochemistry is completely negative, the mutation rate of TP53 gene is higher, and further gene sequencing is recommended to determine the mutation status.
4.Clinicopathological and molecular genetic heterogeneity of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young
Xiaoli SU ; Jiawen WU ; Pingling WANG ; Liwen HU ; Yupeng CHEN ; Caihong REN ; Fangling SONG ; Hangrui LIN ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Pathology 2025;54(11):1163-1171
Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.
5.Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis
Xiaoling LI ; Hua ZHANG ; Chengcong HU ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Liwen HU ; Yupeng CHEN ; Qian HUANG ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Oncology 2025;47(3):275-282
Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P<0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.
6.Clinicopathological features and molecular phenotypes of pleomorphic xanthoas-trocytoma:an analysis of 79 cases
Yu ZHANG ; Weiwei FU ; Yupeng CHEN ; Hong LI ; Weiping SHI ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(2):221-227,232
Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1%),and CDKN2A homozygous deletion(36.8%)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.
7.Clinicopathological and molecular genetic heterogeneity of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young
Xiaoli SU ; Jiawen WU ; Pingling WANG ; Liwen HU ; Yupeng CHEN ; Caihong REN ; Fangling SONG ; Hangrui LIN ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Pathology 2025;54(11):1163-1171
Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.
8.Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis
Xiaoling LI ; Hua ZHANG ; Chengcong HU ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Liwen HU ; Yupeng CHEN ; Qian HUANG ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Oncology 2025;47(3):275-282
Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P<0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.
9.Clinicopathological features and molecular phenotypes of pleomorphic xanthoas-trocytoma:an analysis of 79 cases
Yu ZHANG ; Weiwei FU ; Yupeng CHEN ; Hong LI ; Weiping SHI ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(2):221-227,232
Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1%),and CDKN2A homozygous deletion(36.8%)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.
10.Construction and Validation of A Nomogram Prediction Model of Febrile Seizure in Children
Cheng WANG ; Xingfu WEI ; Meitao ZHAO
Journal of Medical Research 2025;54(3):73-79
Objective To investigate the risk factors of febrile seizures(FS)in children,construct a visualization nomogram predic-tion model of FS and verify its effectiveness.Methods A retrospective analysis was conducted on the clinical data of 1320 children with fever admitted to the Gansu Provincial Maternity and Child-care Hospital(Gansu Provincial Central Hospital)from January 2019 to De-cember 2022.The samples were randomly divided into the training set and the validation set at a ratio of 7∶3.The clinical characteristics and laboratory examination of the two groups were compared.LASSO regression was used to select the risk factors for FS,and multivariate Logistic regression analysis was performed on the predictors,and construction a prediction mode,and the discrimination,calibration and clinical applicability of the model were evaluated.Results The results showed that age,low body weight,peak temperature,diurnal changes in onset,upper respiratory tract infection,serum sodium,serum calcium,white blood cell,procalcitonin were independent risk factors for FS in children.A predictive model was constructed and a nomogram was developed with these factors.The area under the re-ceiver operating characteristic(ROC)curve of the training set and the validation set were 0.870(95%CI:0.847-0.893)and 0.855(95%CI:0.817-0.894),respectively.The calibration plots and Hosmer-Lemeshow goodness-of-fit test showed its satisfactory cali-bration.The decision curve analysis(DCA)curve showed that the model provided a good net benefit with threshold probabilities when training set was>5%,while in the validation set it was>8%.Conclusion The risk prediction model based on LASSO-Logistic re-gression analysis can provide reference for early risk assessment of children with FS.

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