1.Construction and evaluation of a novel KPC mouse model of type 2 diabetes mellitus comorbid with spontaneous pancreatic cancer
Xuehuan HUANG ; Caihui ZHAO ; Yongning XU ; Haochang YANG ; Wen QIN
Journal of Clinical Hepatology 2026;42(4):908-917
ObjectiveTo construct a novel KPC mouse model of type 2 diabetes mellitus (T2DM) comorbid with spontaneous pancreatic cancer based on the gene editing-metabolic intervention dual-driven strategy, and to compare it with traditional models. MethodsA total of 14 male KPC mice were randomly divided into novel model group (T2DM-KPC group with 7 mice) and control group (KPC group with 7 mice), and 14 male BALB/c-nu nude mice were randomly divided into traditional model group (T2DM-pancreatic cancer group with 7 mice) and control group (pancreatic cancer group with 7 mice). The mice in the KPC group and the pancreatic cancer group were fed with normal diet, and those in the T2DM-KPC group and the T2DM-pancreatic cancer group were fed with a high-fat diet. After 4 weeks, the mice in the T2DM-KPC group and the T2DM-pancreatic cancer group were given intraperitoneal injection of streptozotocin. Subsequently, the mice in the KPC group and the T2DM-KPC group developed primary pancreatic tumor spontaneously over time, while those in the T2DM-pancreatic cancer group and the pancreatic cancer group were inoculated with tumor cells to form subcutaneous tumor xenograft at 2 weeks after stabilization of blood glucose. The 4 groups were observed in terms of tumor formation rate, tumor formation time, body weight, and the change in blood glucose; RNA sequencing was performed for tumors from the KPC group and the T2DM-KPC group, and then molecular subtyping was performed; HE staining, Masson staining, and immunohistochemical staining were used to assess the histopathological features and tumor microenvironment of pancreatic tumor from the T2DM-KPC group, which were compared with those of the T2DM-pancreatic cancer group. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Fisher’s exact test was used for comparison of categorical data between multiple groups. ResultsThe T2DM-KPC group had a tumor formation rate of 85.71% and a tumor formation time of 104.40±2.87 days, while the T2DM-pancreatic cancer group had a tumor formation rate of 71.43% and a tumor formation time of 95.20±9.47 days, and there were no significant differences between the two groups in tumor formation rate, tumor formation time, body weight, and blood glucose (all P>0.05). Molecular subtyping showed that the model in the KPC group highly resembled the pancreatic progenitor subtype of human pancreatic ductal adenocarcinoma (PDAC), and the model in the T2DM-KPC group highly resembled the immunogenic subtype of PDAC. HE staining showed that tumor cells in the T2DM-KPC group were arranged into glandular tubular structures of varying shapes, exhibiting significant cellular atypia, and this model faithfully recapitulated the pathological features of primary pancreatic cancer and showed greater invasiveness than the KPC group. Immunohistochemical staining and Masson staining showed that compared with the T2DM-pancreatic cancer group, the T2DM-KPC group had significantly higher degrees of tumor proliferation (assessed by Ki-67 expression) and fibrosis (assessed by α-SMA and Masson) (all P<0.05), suggesting that the mouse model in the T2DM-KPC group could better recapitulate the features of hyperproliferation and pronounced desmoplasia in human pancreatic cancer. ConclusionA novel KPC mouse model of T2DM comorbid with spontaneous pancreatic cancer is successfully constructed in this study. This model can accurately mimic the histopathological architecture and stromal microenvironment of T2DM comorbid with pancreatic cancer, realize the longitudinal simulation of the progression of pancreatic tissue from intraepithelial neoplasia to invasive carcinoma and metastasis in the presence of T2DM, and support the translational research on immunotherapy, thereby providing a novel experimental carrier for in vivo studies on spontaneous pancreatic cancer in T2DM.
2.MRI combined with serum carbohydrate antigen 125 and human epididymis protein 4 for differential diagnosis of type Ⅰ and Ⅱ epithelial ovarian cancers
Xuehuan ZHAO ; Qiumei LIU ; Jie DING ; Zhenzhen WANG ; Jianli LIU ; Yinghui LIU
Chinese Journal of Interventional Imaging and Therapy 2024;21(9):549-552
Objective To observe the value of MRI combined with serum carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)for differential diagnosis of type Ⅰ and Ⅱ epithelial ovarian cancers(EOC).Methods Totally 87 EOC patients were retrospectively enrolled.According to pathology,35 cases of type Ⅰ EOC were taken as type Ⅰ group,while 52 cases of type Ⅱ EOC were taken as type Ⅱ group.Conventional MRI manifestations and apparent diffusion coefficient(ADC)value of lesions,as well as CA125 and HE4 were compared between groups,and their efficacy for differential diagnosis of type Ⅰ and Ⅱ EOC were analyzed.Results Significant differences of conventional MRI manifestations of lesions,including composition,mural nodules,peritoneal diffusion and lymph node metastasis,of ADC value of lesions,also of patients'CA125 and HE4 were found between groups(all P<0.05).The area under the curve(AUC)of conventional MRI manifestations and ADC value of lesions,patients'CA125 and HE4 for distinguishing typeⅠ and type Ⅱ EOC was 0.694,0.730,0.670 and 0.708,respectively,while of the combination of the above four was 0.865,higher than that of each one alone(Z=3.008,2.138,3.005,2.746,all P<0.05).Conclusion MRI combined with CA125 and HE4 was helpful for differential diagnosis of type Ⅰ and Ⅱ EOC.
3.Pathogenesis Analysis of Type-B Aortic Dissection Based on Morphological and Hemodynamic Parameters
Xuehuan ZHANG ; Zhenfeng LI ; Huanming XU ; Yuqian MEI ; Tianyang ZHAO ; Sida BAO ; Jiang XIONG ; Duanduan CHEN
Journal of Medical Biomechanics 2020;35(3):E271-E275
Objective To investigate the pathogenesis of type-B aortic dissection by using morphological analysis and computational fluid dynamics (CFD) method, so as to provide evidence for the effective prediction of type-B aortic dissection. Methods Six primary type-B dissection cases scanned by CT (dissection group) and six normal cases applied to black-blood MRI (control group) were included in this study and patient-specific three-dimensional (3D) models of aorta were established through image segmentation and 3D reconstruction. The pre-type-B dissection aortas were constructed by applying the scaling algorithm to shrink the dissection and then compared with subjects in control group. The differences between morphological parameters and hemodynamic parameters of the two groups were compared. Results Compared with the normal cases, the area of the descending aorta increased dramatically in dissection group [(892.03±263.78) mm2 vs (523.67±64.10) mm2, P=0.036]. A significant decrease in angle of the left subclavian artery occurred (66.62°±20.11° vs 100.40°±15.35°, P=0.036). The tortuosity of the aorta also had an obvious increase (0.37°±0.07° vs 0.21°±0.51°, P=0.011). The time-averaged wall shear stress (TAWSS) in dissection group was obviously higher than that in control group; the flow in the dissection region was vortex flow at low speed and the oscillating shear index (OSI) was higher. Conclusions The results of this study can be used to provide guidance for the early diagnosis and treatment of type-B aortic dissection.
4.High resolution CT in evaluation of anatomic relationship between labyrinth segment of facial canal and cochlea
Heyu DING ; Pengfei ZHAO ; Han LYU ; Xuehuan LIU ; Peng ZHANG ; Zheng WANG ; Mei JIN ; Hao WANG ; Zhenghan YANG ; Shusheng GONG ; Zhenchang WANG
Chinese Journal of Medical Imaging Technology 2018;34(3):331-334
Objective To investigate the value of high resolution CT (HRCT) in displaying the anatomic relationship between labyrinth segment of facial canal and cochlea.Methods Totally 110 patients (220 ears) who underwent HRCT were collected.The original images were transferred to workstation for image processing.MPR images were acquired.The anatomic relationship between labyrinth segment of facial canal and cochlea was observed in oblique coronal MPR images.The bony septum between labyrinth segment of facial canal and cochlea was assessed as definite defect (Type Ⅰ),doubtful defect (Type Ⅱ) or complete (Type Ⅲ),respectively.Results There were 71 ears (71/220,32.27%) of Type Ⅰ,diameters of bone fissure ranged from 0.3-1.3 mm (average diameters [0.64±0.26]mm),86 ears (86/220,39.09%) of Type Ⅱ and 63 ears (63/220,28.64%) of Type Ⅲ,with bony septum thickness ranged from 0.3-1.0 mm (average thickness [0.68±0.15]mm).No statistical difference of rates of the above three types was found between different genders,among age groups and between both side of ears (all P>0.05).Conclusion HRCT is a reliable method to show the anatomic relationship between labyrinth segment of facial canal and cochlea.
5. Review on methods in the disease burden assessment attributable to household air pollution
Xuehuan GAO ; Renjie CHEN ; Haidong KAN ; Wei LIU ; Furong DENG ; Jingguang LI ; Yinping ZHANG ; Yihan LU ; Zhuohui ZHAO
Chinese Journal of Preventive Medicine 2018;52(12):1315-1320
In the past decades, people's work and life styles have dramatically changed during the rapid economic development and urbanization in China. A national survey reported that Chinese adults spend an average of 81% of daily time in indoor environment. Exposure to indoor air pollution plays key roles for human health but is likely to be neglected due on the relatively lower concentration levels and lower awareness among common people. Till now, published studies focus more on the pollution levels or the toxicological effects of indoor air pollutants but there is a lack of disease burden assessment attributable to indoor air pollution. In this review, several international studies were introduced on the disease burden estimation attributable to indoor air pollution, as well as the estimation methods. The current situation of national study was also reviewed. The strengths and limitations of the representative international studies were discussed. This review is helpful in providing data to guide the research on disease burden assessment attributable to indoor air pollution in China, and further helps to prioritize the indoor air pollution control based on disease burden ranking among pollutants and motivate public policies to protect the public health.

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