1.Establishment of genomic detection system for Alzheimer′s disease risk based on time-of-flight mass spectrometry
Yuyan KUANG ; Ting ZHANG ; Wenyan GE ; Huimin GUO ; Qingmin RAO ; Yongyin HE ; Qiang WANG ; Xiaomei ZHONG ; Yuping NING ; Yulong LIN ; Haiying LIU
Chinese Journal of Laboratory Medicine 2025;48(12):1571-1580
Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.
2.Establishment of genomic detection system for Alzheimer′s disease risk based on time-of-flight mass spectrometry
Yuyan KUANG ; Ting ZHANG ; Wenyan GE ; Huimin GUO ; Qingmin RAO ; Yongyin HE ; Qiang WANG ; Xiaomei ZHONG ; Yuping NING ; Yulong LIN ; Haiying LIU
Chinese Journal of Laboratory Medicine 2025;48(12):1571-1580
Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.
3.Impact of a modified CARG model guiding anticancer drug dose adjustments on adverse events in elderly cancer patients
Yuping GE ; Yuwei HUA ; Lina WANG ; Xiufeng HOU ; Hua SONG ; Xinying GUO ; Yuan ZHANG ; Yanan WANG ; Mei GUAN
Basic & Clinical Medicine 2025;45(10):1277-1283
Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P>0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.
4.Advances in pharmacotherapy for angiosarcoma
Yuping GE ; Ying LIU ; Lin ZHAO
Basic & Clinical Medicine 2024;44(10):1363-1367
Angiosarcoma(AS)is a rare soft tissue sarcoma originating from vascular or lymphatic endothelial cells,accounting for less than 1% of soft tissue sarcomas.It is most common in skin and surface of soft tissue.The diagno-sis of AS is based on pathology,and the expression of CD31,ERG and CD34 is commonly positive in immuno-his-tochemistry.Staging is performed according to the American Joint Committee on Cancer(AJCC)criteria for soft tis-sue sarcoma.Radical surgery is the primary therapy for locally confined disease.For un-resectable or metastatic an-giosarcoma,chemotherapy is the main treatment method.Targeted therapy and immunotherapy have developed rap-idly in recent years,and the combined therapy of different types of chemotherapy drug has been the focus of optimi-zation in the future.
5.Investigation on Clinical Oncology Teaching Among Medical Students
Zhiyang ZHANG ; Lin ZHAO ; Yajuan SHAO ; Xiang WANG ; Ningning LI ; Xiaohong NING ; Yuping GE
Medical Journal of Peking Union Medical College Hospital 2024;15(1):223-228
6.Preparation of N- 18F-fluoroethyl-tofacitinib and its application in the imaging of rheumatoid arthritis
Yixiang ZHOU ; Ge YAN ; Donghui PAN ; Yuping XU ; Junjie YAN ; Xinyu WANG ; Min YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(4):231-236
Objective:To synthesize N- 18F-fluoroethyl-tofacitinib, and explore its feasibility in the diagnosis of rheumatoid arthritis (RA). Methods:The " two-step method" was used to modify tofacitinib with 18F-fluoroethyl, and the labeling rate and radiochemical purity of the probe were measured by high performance liquid chromatography (HPLC), and the stabilities of the probe in vivo and in vitro were investigated. BALB/c mice (normal group; n=3) and collagen-induced arthritis (CIA) model mice (CIA group; n=3) were injected with N- 18F-fluoroethyl-tofacitinib and CIA model mice injected with tofacitirrib and N- 18F-fluoroethyl-tofacitinib were as blocking group ( n=3). All mice underwent microPET imaging and the percentage injection dose per gram of tissue (%ID/g) and the uptake ratio of inflamed joints to muscle (T/M) were calculated. One-way analysis of variance and the least significant difference (LSD) t test were used to analyze the data. Results:The synthesis time of N- 18F-fluoroethyl-tofacitinib was about 120 min, with the yield approximately 1%, the specific activity >13.6 GBq/μmol, and the radiochemical purity >99%. After the probe incubated with PBS, plasma or in vivo for 2 h, the radiochemical purity was still more than 95%. MicroPET imaging showed that 30 min after injection, the uptake of N- 18F-fluoroethyl-tofacitinib in the inflamed joints of CIA group was higher than that of normal group and blocking group ((10.22±1.64), (2.71±0.26) and (2.81±0.33) %ID/g; F=58.26, t values: 7.83, 7.67, P values: 0.001, 0.002). The T/M of CIA group was also higher than that of normal group and blocking group (24.73±5.77, 2.75±1.36 and 2.89±0.54; F=40.64, t values: 6.42, 6.53, P values: 0.003, 0.003). Conclusions:N- 18F-fluoroethyl-tofacitinib is successfully prepared and it is stable in vitro with good imaging performance in vivo. It may be used in clinic for the diagnosis of RA.
7.Preliminary study on prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on cranial radiomics
Chuan Ding ; Xiaohu Li ; Jun Wang ; Hongwen Li ; Yuping Wang ; Changliang Yu ; Yaqiong Ge ; Haibao Wang ; Bin Liu
Acta Universitatis Medicinalis Anhui 2022;57(1):161-164
Objective :
To study the best machine learning method for early prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on head CT plain scan.
Methods :
The CT images of 130 patients with cerebral hemorrhage were retrospectively analyzed , and the texture features of the head CT plain scan were extracted. The classifier was trained by selecting the features , and the six classic machine learning methods were crossvalidated to evaluate the stability and performanceof predicting cerebral hemorrhage hematoma expansion.
Results:
The prediction performance of support vector machine (SVM⁃Radial) (AUC 0. 714 ± 0. 144 , accuracy 0. 723 ± 0. 109) , generalized linear model ( GLM) prediction performance ( AUC 0. 643 ± 0. 125 , accuracy 0. 587 ± 0. 136) , random forest (RF) prediction performance (AUC 0. 686 ± 0. 128 , accuracy 0. 680 ± 0. 130) , k ⁃nearest neighbor (kNN) prediction performance ( AUC 0. 657 ± 7C 15 , accuracy 0. 639 ± 39 performance 19) , gradient boosting tree algorithm (GBM) Prediction performance ( AUC 0. 718 ± 0. 141 , accuracy 0. 670 ± 0. 126) , neural network (NNet) prediction performance (AUC 0. 659 ± 0. 162 , accuracy 0. 680 ± 0. 130) , in which support vector machines showed high prediction performance , generalized linear model showed low predictive performance.
Conclusion
Among the six machine learning methods based on cranial CT radiomics to predict early hematoma expansion in hypertensive intracerebral hemorrhage , support vector machine (SVM⁃Radial) has the best predictive performance and has potential clinical application value.
8.Ovarian metastases of pancreatic ductal adenocarcinomas: the clinicopathological characteristics and outcomes of 10 cases
Xiang WANG ; Yan YOU ; Yuping GE ; Hongyan YING ; Yuejuan CHENG ; Chunmei BAI
Chinese Journal of Oncology 2020;42(4):331-335
Objective:To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma.Methods:Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed.Results:The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months.Conclusions:Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.
9.Ovarian metastases of pancreatic ductal adenocarcinomas: the clinicopathological characteristics and outcomes of 10 cases
Xiang WANG ; Yan YOU ; Yuping GE ; Hongyan YING ; Yuejuan CHENG ; Chunmei BAI
Chinese Journal of Oncology 2020;42(4):331-335
Objective:To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma.Methods:Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed.Results:The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months.Conclusions:Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.
10. Association between atherogenic index of plasma and renal function impairment in patients with gout
Ruirui SONG ; Kahaer MAYNA ; Bei ZHANG ; Xiaobo ZHANG ; Ying LU ; Ge TIAN ; Shanshan YANG ; Yuping SUN
Chinese Journal of Endocrinology and Metabolism 2019;35(12):1043-1049
Objective:
To study the relationship between atherogenic index of plasma (AIP)and renal impairment in male patients with gout.
Methods:
A retrospective analysis of 821 male subjects was conducted to measure the relevant biochemical indicators and to calculate the AIP, endogenous creatinine-clearance rate (Ccr), and estimated glomerular filtration rate (eGFR). EpiData 3.1 software was used for data entry, SPSS21.0 was used for statistical analysis, and GraphPad Prism 6.0 software was used for charts.
Results:
Compared with control group, AIP, serum uric acid, triglyceride in gout group were significantly higher (all


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