1.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.Application of color doppler flow imaging in the diagnosis of ocular toxocariasis in children
Wei CHEN ; Wenli YANG ; Jinghua LIU ; Dongjun LI ; Ziyang WANG ; Qi ZHAO ; Yifeng LI ; Rui CUI ; Lin SHEN ; Qian LIU
Chinese Journal of Ocular Fundus Diseases 2024;40(1):39-43
Objective:To summarize the characteristics of color doppler flow imaging (CDFI) of ocular toxocariasis (OT) in children.Methods:A retrospective clinical study. From July 2014 to June 2020, 61 OT patients with 61 eyes diagnosed through clinical and laboratory testing in the Department of Ophthalmology of Beijing Tongren Hospital of Capital Medical University were included in the study. There were 45 males with 45 eyes and 16 females with 16 eye (male: female=2.81:1). Age were (6.93±2.50) years. The right eye and left eye were 29 and 32 eyes, respectively. Both eyes of the patient underwent two-dimensional ultrasound and CDFI examination. Two dimensional ultrasound was used to estimate the axial length (AL) of the affected eyes and healthy eyes on the opposite side. Among them, 52 cases were measured for AL using optical biometry and/or A-mode ultrasound. Vitreoretinal surgery was performed within one week after ultrasound examination. Two-dimensional ultrasound was used to observe the morphology of vitreous opacity, its connection to the eyeball wall, and whether posterior vitreous detachment and retinal detachment have occurred. CDFI examination was used to observe the presence of blood flow signals on the pathological membrane. The detection rates of different forms of vitreous opacity and traction retinal detachment were calculated. The location of proliferative lesions in the eye was analyzed. Paired t-test was performed to compare the AL of the affected eye and the healthy eye on the opposite side. Perform Kappa consistency test on the location of proliferative lesions was used during CDFI examination and vitreoretinal surgery. Results:All affected eyes have varying degrees of vitreous opacity. Among them, 23 eyes (37.7%, 23/61) showed typical "Christmas tree" like turbidity; 27 eyes (44.3%, 27/61) had clustered and striped echoes; 9 eyes (14.8%, 9/61) had weak punctate and strip echoes. Two eyes (3.3%, 2/61) showed a large amount of dense punctate and strip-shaped echoes. There were 50 eyes (82.0%, 50/61) with traction retinal detachment, of which 46 eyes (92.0%, 46/50) had visible blood flow signals on the detached retina, and the remaining 4 eyes (8.0%, 4/50) had no blood flow signals. During CDFI and surgery, there were 5 (8.2%, 5/61) and 4 (6.6%, 4/61) eyes with visible proliferative lesions in the periphery, respectively; 18 (29.5%, 18/61) and 14 (23.0%, 14/61) eyes were distributed in the posterior pole, respectively; there were 38 (62.3%, 38/61) and 43 (70.5%, 43/61) eyes with both peripheral and posterior polar regions, respectively. The consistency between CDFI and surgery in detecting the location of proliferative lesions was good ( κ=0.832, 95% confidence interval 0.691-0.973, P<0.001). The two-dimensional ultrasound measurement results showed that the AL of the affected eye was shorter than that of the contralateral healthy eye in 46 cases (75.4%, 46/61). Among the 52 patients who underwent AL biometry, the AL of the affected eye was shorter than that of the contralateral healthy eye by (0.63±0.68) mm, and the difference was statistically significant ( t=-6.738, P<0.05). Conclusions:CDFI can clearly display various intraocular lesions (vitreous opacity and traction retinal detachment) and eyeball sizes in children with OT. Vitreous opacity is often manifested as "Christmas tree" like, clustered, strip-shaped.
5.Effects of Yishen Daluo Decoction on the serum levels of the glycolysis-related protein HIF-1α and cytokines in patients with relapsing-remitting multiple sclerosis
Jia LIU ; Xiaorui GUAN ; Jingze ZHANG ; Qi YANG ; Yifeng RUI ; Ying GAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):9-15
Objective We aimed to assess the serum levels of the glycolysis-related protein hypoxia-inducible factor-1α(HIF-1α)and cytokines in patients with relapsing-remitting multiple sclerosis(RRMS)before and after treatment with the traditional Chinese medicine Yishen Daluo Decoction,as well as their correlation with clinical parameters,and explore the immune regulatory mechanism of Yishen Daluo Decoction on multiple sclerosis.Methods Twenty-eight patients with RRMS in remission recruited from May 2018 to January 2022 in the Multiple Sclerosis Clinic at Dongzhimen Hospital,Beijing University of Chinese Medicine were retrospectively included.Comparisons were made with paired samples from 13 of them before and after Yishen Daluo Decoction treatment.A total of 20 gender-and age-matched healthy controls(HCs)were also recruited.Clinical information was collected from all of the subjects,and the neurological impairments of RRMS patients were assessed with the Expanded Disability Status Scale(EDSS)score.ELISA and SP-X multiplex cytokine assays were used to measure the serum levels of HIF-1 α and 10 cytokines(IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-22,IFN-γ,and TNF-α),respectively.Spearman's method was used to analyze the correlation between the serum levels of HIF-1α and cytokines,and the correlation between the serum levels of HIF-1α and cytokines and patients'clinical indicators,including disease duration,the number of attacks,and the EDSS score.Results Serum HIF-1α,IL-4,IL-6,IL-8,IL-10,IL-12p70,IFN-γ,and TNF-α levels in the RRMS group were significantly higher than those in the HC group(P<0.05).Serum levels of HIF-1α,IL-4,IL-6,and IL-12p70 in the Yishen Daluo Decoction-pre group were significantly higher than those in the Yishen Daluo Decoction-post group(P<0.05).In addition,the serum HIF-1α level was positively correlated with IL-6(r=0.452,P=0.016)and TNF-α(r=0.524,P=0.004)levels in patients with RRMS.The IFN-γ level was negatively correlated with the EDSS score(r=-0.423,P=0.025),the IL-4 level was negatively correlated with disease duration(r=-0.385,P=0.043),and the TNF-α level was positively correlated with disease duration(r=0.397,P=0.037).Conclusion The regulatory mechanism of Yishen Daluo Decoction on immune imbalance in RRMS may be related to its ability to reduce the serum levels of the glycolysis-related protein HIF-1α in RRMS patients.It is also related to the levels of various inflammatory cytokines.
6.Analysis of the feasibility of measurements and characteristics of intraocular lens tilt using swept-source optical coherence tomography biometer
Qi ZHAO ; Wenli YANG ; Dongjun LI ; Ziyang WANG ; Wei CHEN ; Yifeng LI ; Rui CUI ; Lin SHEN ; Lei LI ; Junfang XIAN
Chinese Journal of Experimental Ophthalmology 2023;41(6):554-560
Objective:To evaluate the feasibility of measurement and characteristics of intraocular lens (IOL) tilt using the swept-source optical coherence tomography (SS-OCT) biometer (IOLMaster 700) and to explore its potentially relevant parameters.Methods:A cross-sectional study was conducted.Two hundred and forty-two eyes (119 right eyes, 123 left eyes) of 185 patients after phacoemulsification and IOL implantation were included in Beijing Tongren Hospital from July to September 2018.The IOL position, angle κ, angle α, corneal curvature, anterior chamber depth (ACD), pupil diameter (PD), and axial length (AL) were obtained by IOLMaster 700, and the IOL tilt direction and magnitude were calculated.The within-subject standard deviation and intraclass correlation coefficient were used to evaluate the repeatability of three IOL tilt measurements.Binocular symmetry of IOL tilt and the correlation between IOL tilt and different influencing factors were evaluated by Pearson linear correlation analysis or Spearman rank correlation analysis.Influencing factors for IOL tilt were assessed by multiple linear regression analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2018-049). Patients were informed of the purpose and methods of this study and signed the written informed consent.Results:The repeatability of IOL tilt measurements was excellent with a within-subject standard deviation of 5.16° for IOL tilt direction and 0.13° for IOL tilt magnitude.IOL tilt was mirror symmetric in both eyes.The IOL tilt direction in right eyes ranged from -89.60° to 87.53° with a mean of (18.85±29.65)°, and the tilt magnitude ranged from 1.32° to 7.05° with a mean of (4.16±1.26)°.The IOL tilt direction in left eyes ranged from -84.30° to 89.44° with a mean of (21.17±32.38)°, and the tilt magnitude ranged from 0.58° to 7.40° with a mean of (3.80±1.31)°.There were moderate and weak positive correlations of IOL tilt direction and tilt magnitude between both eyes ( r=0.473, P<0.001; r=0.335, P=0.011). IOL tilt magnitude was weakly positively correlated with angle α and IOL diopter ( rs=0.272, P=0.003; r=0.285, P=0.002), and was weakly negatively correlated with ACD, PD and AL ( r=-0.303, P=0.001; r=-0.233, P=0.011; rs=-0.331, P<0.001). In backward stepwise regression analysis, the regression equation of IOL tilt magnitude, angle α, ACD, PD, AL and IOL diopter in multiple linear regression analysis was as follows: IOL tilt magnitude=10.503+ 1.456×angle α-0.532×ACD-0.196×AL ( R2=0.400; F=8.588, P<0.001). Conclusions:The SS-OCT biometer can be an effective method to assess IOL tilt.IOL tilt is mirror symmetric between the right eyes and left eyes.
7.Feasibility of CT quantitative evaluation for myocardial strain in patients before transcatheter aortic valve replacement
Wentao ZHANG ; Zhen ZHOU ; Yifeng GAO ; Rui WANG ; Lei XU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1245-1250
Objective To explore the feasibility of CT evaluation of myocardial strain in patients undergoing transcatheter aortic valve replacement(TAVR)with cardiac magnetic resonance(CMR)as the reference standard.Methods A retrospective study was conducted on 43 patients undergoing cardiac CT examination before TAVR in our hospital from June to December 2022.The cardiac CT and CMR data were collected,and myocardial strain parameters were measured.The cardiac function and strain parameters based on cardiac CT were compared with the parame-ters of CMR,including left ventricular ejection fraction(LVEF),left ventricular end-diastolic vol-ume(LVEDV),left ventricular end-systolic volume(LVESV),diastolic myocardial mass(MASS),cardiac output,global peak longitudinal strain(GPLS),global peak circumferential strain(GPCS)and global peak radial strain(GPRS).Results The values of LVEF and cardiac output derived from cardiac CT were close to those from CMR(P>0.05),while the values of LVEDV,LVESV and MASS from cardiac CT were significantly higher than those from CMR,and those of GPLS,GCPS and GRPS from cardiac CT were obviously lower than those from CMR(P<0.01).Pearson correlation analysis showed that the LVEF,LVEDV,LVESV,MASS,GCPS and GRPS derived from cardiac CT had strongly positive correlation with those from CMR(r=0.908,r=0.917,r=0.947,r=0.954,r=0.856,r=0.864,P<0.01),while the cardiac output and GPLS had a moderate positive correlation(r=0.763,r=0.656,P<0.01).Bland-Altman analysis showed that the LVEF,cardiac output,GPLS,GCPS and GRPS derived from cardiac CT had small biases with those from CMR.Conclusion Cardiac CT quantitative evaluation of cardiac function and strain is feasible in patients undergoing TAVR,and the cardiac function parameters of cardiac CT have good agreement with those from CMR,while the myocardial strain parameters are lower than those from CMR.
8.Ultrasonographic features of adenoma of the nonpigmented ciliary epithelium
Dongjun LI ; Wenli YANG ; Wenbin WEI ; Xiaolin XU ; Ziyang WANG ; Wei CHEN ; Qi ZHAO ; Yifeng LI ; Rui CUI ; Lin SHEN ; Qian LIU ; Chuanchuan WEI
Chinese Journal of Ocular Fundus Diseases 2022;38(3):191-196
Objective:To analyze the ultrasonographic features of adenoma of the nonpigmented ciliary epithelium (ANPCE).Methods:A retrospective series of case studies. From January 2014 to October 2021, 31 patients (31 eyes) with ANPCE (ANPCE group) were diagnosed in the eye center of Beijing Tongren Eye Center of Beijing Tongren Hospital, Capital Medical University, and 17 patients (17 eyes) with ciliary body melanoma (control group) diagnosed at the same time were selected as the control group. There was no significant difference in age ( t=-0.564) and sex composition ratio ( χ 2=0.182) between the two groups ( P=0.576, 0.670). All patients underwent ultrasound biomicroscopy to obtain the measurement parameters: tumor height, maximum basal diameter, maximum diameter, ratio of maximum diameter to basal diameter and ratio of maximum diameter to height; tumor location, shape, internal echogenicity intensity, echogenicity uniformity, degree of sound attenuation, invasion of iris, anterior displacement of the iris, lens subluxation were observed. The measurement parameters and observation indexes of the two groups were compared by independent sample t-test and χ 2 test. Receiver operating characteristic (ROC) curve was drawn, area under the ROC curve (AUC) was determined, and parameter indicators with differential diagnosis value were screened. Results:The maximum diameter, height, maximum basal diameter, ratio of the maximum diameter to the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumors in the ANPCE group and the control group were 5.64±0.98 mm, 4.24±0.59 mm, 3.66±0.71 mm, 1.58±0.34, 1.34±0.19 and 7.82±2.03 mm, 4.47±2.44 mm, 7.02±1.96 mm, 1.13±0.16, 2.09±1.06. The maximum diameter, the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumor in the ANPCE group were all smaller than those of the control group, and the ratio of the maximum diameter to the maximum basal diameter was greater than that of the control group, and the differences were statistically significant ( t=-4.159,-6.808, -2.924, 6.257; P<0.05). The tumors in the ANPCE group were mainly spherical (87.1%, 27/31), with no significant acoustic attenuation (77.4%, 24/31), less invading the root iris (77.4%, 24/31), and the tumors were mostly located in the ciliary body coronal (74.2%, 23/31); tumors in the control group were mainly hemispherical (47.1%, 8/17) or spherical (47.1%, 8/17), with significant sound attenuation (76.5%, 13/17), most of the tumors invaded the iris (70.6%, 12/17), and the tumors were mostly located from the pars plana to the coronal (76.5%, 13/17). There were statistically significant differences in the position, shape, sound attenuation degree, and whether it invaded the iris between the two groups of eyes ( χ 2=15.132, 19.767, 13.118, 10.581; P<0.05). The results of ROC curve analysis showed that the ratio of the largest diameter to the largest base diameter, the degree of sound attenuation and the AUC of whether the iris was violated were higher, which were 0.881, 0.769, and 0.740, respectively. Conclusions:Ultrasound biomicroscopy is helpful in the diagnosis and differential diagnosis of ANPCE and ciliary body melanoma. The ratio of maximum diameter to maximum basal diameter, the degree of sound attenuation and whether it invades the root iris are important parameters to distinguish the two tumors.
9.Analysis of ultrasonic diagnostic features of juxtapapillary capillary hemangioma
Yifeng LI ; Wenli YANG ; Dongjun LI ; Ziyang WANG ; Wei CHEN ; Qi ZHAO ; Rui CUI ; Lin SHEN ; Qian LIU ; Wenbin WEI ; Junfang XIAN
Chinese Journal of Ultrasonography 2021;30(2):161-166
Objective:To discuss the characteristics of ultrasound diagnosis of optic disc capillary hemangioma.Methods:The study analyzed retrospectively 7 cases of optic disc capillary hemangioma diagnosed in the Beijing Tongren Hospital from 2015 to 2018. The size, morphology, internal echo, and secondary changes of the lesion were analyzed during ultrasound examination.Color Doppler flow imaging was used to check the blood flow in the lesion.Results:Pre-optic disc occupying lesions could be detected in the ultrasound images of the 7 cases. Lesion size: average base diameters (5.39±1.90)mm×(4.79±1.28)mm, average height (3.61±1.37)mm. Lesion morphology: 5 cases were round, and 2 cases were irregular. Echo within the lesion: 3 cases had medium echo inside the lesion, and 4 cases had high echo inside the lesion. Internal echo characteristics: 5 cases had uniform echo, and 2 cases had uneven echo. Secondary changes: 6 cases had secondary retinal detachment and vitreous opacity, and 1 cases was accompanied by retinal hemangioma in other parts. In all cases, blood flow signals could be detected inside the space-occupying lesions, which were in the form of branches, stripes or spots, and the blood flow spectrum showed a parallel spectrum of arteries and veins.Conclusions:Ultrasound examination of optic disc capillary hemangioma has certain characteristics, which can provide a valuable follow-up basis for clinical diagnosis.
10.Perfusion characteristics analysis of contrast-enhanced ultrasound in choroidal metastasis and choroidal hemangioma
Dongjun LI ; Wenli YANG ; Ziyang WANG ; Wei CHEN ; Qi ZHAO ; Yifeng LI ; Rui CUI ; Lin SHEN ; Qian LIU ; Yueming LIU ; Wenbin WEI
Chinese Journal of Ultrasonography 2021;30(7):563-568
Objective:To analyze the perfusion characteristics of choroidal metastasis using contrast-enhanced ultrasound, and compare with choroidal hemangioma.Methods:This was a retrospective study.From January 2016 to February 2018 in Beijing Tongren Hospital, a total of 21 eyes from 21 patients who were clinically diagnosed as choroidal metastasis were included as the choroidal metastasis group and 46 eyes from 46 patients who were diagnosed as choroidal hemangioma during the same period were included as the choroidal hemangioma group. All patients underwent contrast-enhanced ultrasound examination, and Sonoliver was used to obtain the data on quantitative parameters of the tumor and the adjacent normal orbital tissues, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (mTT). The quantitative parameters between choroidal metastasis and normal orbital tissues were compared. And the quantitative parameters between choroidal metastasis and choroidal hemangioma were compared. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance.Results:The IMAX of choroidal metastasis was significantly higher than that of normal orbital tissues, while RT, TTP and mTT were significantly shorter than these of normal orbital tissues (all P<0.01). The IMAX of choroidal metastasis was lower than that of choroidal hemangioma, and RT, TTP and mTT were shorter than choroidal hemangioma (all P<0.01). The ROC curve analysis showed that area under curves of the IMAX, RT, TTP and mTT were 0.775 (95% CI=0.666-0.884), 0.970 (95% CI=0.896-0.996), 0.729 (95% CI=0.607-0.831) and 0.992 (95% CI=0.931-1.000) respectively. The sensitivities were 71.7%, 95.7%, 76.1% and 95.7%, and the specificities were 85.7%, 90.5%, 66.7% and 95.2%, respectively. Conclusions:Contrast-enhanced ultrasound can reflect the differences in perfusion characteristics between choroidal metastasis and choroidal hemangioma. RT and mTT are useful parameters in differential diagnosis between the two types of tumors.

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