1.Evaluation of Animal Models with Diminished Ovarian Reserve Based on Clinical Disease and Syndrome Characteristics of Traditional Chinese Medicine and Western Medicine
Mingyue YU ; Ling TANG ; Xiaohui SUN ; Jingjing ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):240-248
ObjectiveWith the development of society and the increasing demand for pregnancy at an advanced age, diminished ovarian reserve (DOR) has attracted wider attention. This disease affects the normal menstruation of women and poses a threat to their mental health. Current research on DOR is still in the initial stage, and advancing research progress in DOR necessitates the construction of effective and clinically relevant animal models. Building on existing literature and integrating the diagnosis criteria of DOR in traditional Chinese medicine (TCM) and Western medicine, this study summarized, analyzed, and evaluated existing models, providing a reference for optimizing DOR animal models. MethodsA retrospective analysis of literature on DOR-related animal models was conducted, and the diagnostic criteria of DOR in TCM and Western medicine were sorted out. By means of evaluation methods of animal models, the clinical relevance of each model to TCM and Western medicine was assessed. ResultsDOR animal models included those based on natural factors, iatrogenic factors, immune factors, metabolic factors, and environmental factors. Among them, the model based on iatrogenic factors, especially models induced by Tripterygium wilfordii preparations, cyclophosphamide, and cisplatin, had a high degree of relevance to both Western medical diseases and TCM syndromes and was confirmed as the optimal modeling method for studying DOR at present. ConclusionThe existing DOR modeling methods mostly have a high degree of clinical relevance to Western medical diseases, while the number of DOR animal models with clear TCM syndromes is very limited. TCM plays an indispensable role in exploring DOR treatment methods. Therefore, the development of DOR animal models related to TCM syndromes should be strengthened, further exploring the potential of TCM and providing strong theoretical support for the application of TCM in DOR treatment.
2.Establishment of Psoriasis Rat Model with Spleen Deficiency and Dampness Obstruction Syndrome Induced by External Dampness Factors
Yating ZHANG ; Haojie SU ; Fanlu LIU ; Panyu ZHOU ; Qing WANG ; Junhong ZHANG ; Jingjing WU ; Ling HAN
Journal of Traditional Chinese Medicine 2025;66(13):1369-1377
ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type), and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group (n=3), common psoriasis group (n=5), spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7), and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7). The spleen deficiency and dampness obstruction syndrome (external dampness type) rat model was established through 32-week exposure to an artificially simulated high-humidity environment, while the common psoriasis model was developed via 7-day topical application of imiquimod cream, and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type). Rats in the normal group were housed under normal humidity conditions. The general state, tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations; the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes; the severity of psoriasis in rats was evaluated through skin pathological changes, psoriasis area and severity index (PASI), proliferating cell nuclear antigen (PCNA) expression and spleen tissue changes; changes in rat CD4+ interferon-γ+ cells (CD4+IFN-γ+ cells), CD4+ tumour necrosis factor-α+ cells (CD4+ TNF-α+ cells), and forkhead framing protein P3+ regulatory T cells (CD3+CD4+FoxP3+ Treg cells) were detected by flow cytometry. ResultsMacroscopically, both the spleen deficiency and dampness obstruction syndrome (external dampness type) group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited manifestations of spleen deficiency and dampness obstruction, including lethargy, huddling behavior, dull and disheveled fur, as well as soft or loose stools and perianal soiling in some individuals; both these two groups displayed enlarged tongue, swollen, and moist tongue texture, accompanied by slippery tongue surface. Microscopically, compared to the common psoriasis group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group showed increased epididymal fat index (P<0.05); compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group demonstrated significantly elevated spleen mass (P<0.05), while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited significantly higher erythema scores, scaling scores, infiltration scores, PASI total scores, and proportions of CD3+CD4+FoxP3+Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05), with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis; the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group displayed significantly increased proportions of CD4+TNF-α+cells compared to the spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05); whereas no significant differences were detected in CD4+IFN-γ+cell proportions among groups (P>0.05). ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.
3.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
4.Speech and language rehabilitation services for children with hearing impairment based on ICF:theoretical framework and service system
Jing ZHOU ; Ling YI ; Jianchao CHEN ; Xuefen CHEN ; Xingxing WEI ; Jingjing CHEN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(7):745-751
Objective Based on the bio-psycho-social model of functioning and health of International Classification of Function-ing,Disability and Health(ICF)framework,this paper systematically analyzes rehabilitation-related policy docu-ments of the World Health Organization(WHO)to explore the theoretical and policy principles,service systems,priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment. Methods Under literature research and policy analysis methods,this paper systematically reviewed the functioning and health framework of ICF,relevant WHO policy reports and American Speech and Hearing Association technical documents,analyzed the current status and needs of rehabilitation services in China,and proposed a theoretical framework,priority areas,and main policy and technical measures for constructing an ICF-based speech and lan-guage rehabilitation service system for children with hearing impairment. Results There were eight major principles for the development of speech and language rehabilitation for children with hearing impairment:child-centered and respect for individual differences,life-cycle support and promoting con-tinuous development,evidence-based practice,multidisciplinary collaboration,building family participation sup-port networks,promoting integrated education and social participation,focusing on cultural sensitivity,and tech-nology-empowered rehabilitation innovation.Five service systems were elaborated,including comprehensive ear-ly screening,diagnosis,and intervention system;family and social support system;multidisciplinary team servic-es system;comprehensive,multi-level speech and language rehabilitation service system;and digitally empow-ered services to build new rehabilitation service models.The priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment were also dis-cussed. Conclusion Based on the bio-psycho-social model of functioning and health of ICF,comprehensive,personalized,con-tinuous,high-quality and universally accessible speech and language rehabilitation services can be developed by implementing measures,such as strengthening policy support,improving service systems,cultivating multidisci-plinary professionals,promoting digital empowerment technologies and enhancing support system,to promote the overall development,social participation and quality of life for children with hearing impairment.
5.Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells
Yao SHI ; Qing WANG ; Junhong ZHANG ; Ling HAN ; Jingjing WU
China Pharmacy 2024;35(18):2252-2257
OBJECTIVE To explore the effects of ursolic acid (UA) on the growth, invasion, apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms. METHODS The effects of different concentrations (0, 5, 10, 15, 20, 25, 30 μmol/L) of UA on the proliferation of SW620 cells for different durations (24, 48, 72 h) were detected by CCK-8 assay; the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA (0,10,15,20 μmol/L) for 10 days. After SW620 cells were treated with different concentrations of UA (0, 10, 15, 20 μmol/L) for 24 hours, flow cytometry, Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells, and the expressions of B cell lymphoma 2 (Bcl-2), cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), p38 MAPK, E-cadherin, N-cadherin and zinc finger transcription factor Snail. The effects of p38 MAPK inhibitor (SB203580) combined with UA on the protein expressions of p-p38 MAPK, Bcl-2 and N-cadherin were investigated. RESULTS Compared with 0 μmol/L UA, the stone5999@163.com survival rates of SW620 cells treated with 5-30 μmol/L UA for 24, 48 and 72 h were significantly decreased (P<0.05). The clone formation rate of cells treated with 15 μmol/L and 20 μmol/L UA was significantly decreased (P<0.05). After being treated with 15 μmol/L and 20 μmol/L UA, the cell apoptosis rate, the protein expressions of cleaved-PARP and E-cadherin, and the phosphorylation of p38 MAPK protein were increased; but the number of transmembrane cells, and the protein expressions of Bcl-2, Snail and N-cadherin were decreased; there was statistical significance in difference of most indexes (P<0.05). Some indexes changed in a concentration-dependent manner (P<0.05). SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin (P<0.05). CONCLUSIONS UA can inhibit the growth, invasion and metastasis of SW620 cells, and induce cell apoptosis, the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.
6.Effect of light pattern on dopamine transporter in the guinea pig retina
Jingjing WANG ; Kai LI ; Kaidi XIANG ; Jun CHEN ; Linlin DU ; Jinliuxing YANG ; Sichen LIU ; Ling WANG ; Xiangui HE
Chinese Journal of Experimental Ophthalmology 2024;42(4):309-314
Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.
7.Predictive value of controlling nutritional status score in the prognosis of patients with advanced diffuse large B-cell lymphoma
Huirong SHAN ; Xicheng CHEN ; Hao ZHANG ; Yuqing MIAO ; Fei WANG ; Yuye SHI ; Ling WANG ; Jingjing YE ; Ziyuan SHEN ; Wei SANG ; Hongfeng GE
Journal of Leukemia & Lymphoma 2024;33(2):104-109
Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
8.Analysis of Vitamin D in Children with Henoch-Schonlein Purpura
Sixiang LIU ; Yongkun HUANG ; Shulan SHI ; Jingjing SUN ; Lisi LUO ; Li WANG ; Yu LING
Journal of Kunming Medical University 2024;45(1):133-135
Objective To analyze the changes of vitamin D in children with Henoch-Schonlein purpura(HSP).Methods 130 children with HSP from Kunming Children's Hospital between July 2022-July 2023 were selected as the study subjects and 100 healthy children were selected during the same period as the control group.The blood samples were collected from the children with HSP and the healthy children.The content of vitamin D was measured by Kunming Kingmed Institute for Clinical Laboratory.Results The content of 25(OH)D in children with HSP was lower than that in healthy children,and the difference was statistically significant(P<0.01).The proportion of vitamin D insufficiency in children with HSP was higher than that in healthy children,and the difference was statistically significant(P<0.01).Conclusion The children with HSP are prone to vitamin D insufficiency.Vitamin D supplementation may provide a new method for the treatment of HSP.
9.Adverse Reactions of Vaccine Vaccination in Children with Special Health Conditions in Kunming and Countermeasures
Zhen XU ; Yu LING ; Sixiang LIU ; Yu SONG ; Yang PENG ; Jingjing SUN
Journal of Kunming Medical University 2024;45(3):141-145
Objective To explore the occurrence of adverse reactions to vaccination in children with special health status in Kunming and the corresponding countermeasures.Methods The information data of 952 children with special health conditions who were vaccinated at the Child Healthcare Department of the Kunming Children's Hospital from October 2021 to February 2023 were collected,and descriptive methods were used for epidemiological analysis.Results The detection rate of adverse reactions in children with special health conditions in Kunming was 10.92%(104/952),all of which were mild adverse reactions.The top three vaccines with the highest detection rates of adverse reactions were adsorbed acellular pertussis-diphtheria-tetanus vaccine(Pertussis-Diphtheria-Tetanus),measles-mumps-rubella attenuated live vaccine(Measles-Mumps-Rubella),and meningococcal polysaccharide vaccine group A and C(Meningococcal A+C),with detection rates of 7.00%,4.14%,and 3.08%,respectively.The detection rate of adverse reactions in children with premature birth,allergy,and anemia after vaccination was higher,with detection rates of 13.87%,11.03%,and 10.05%,respectively.The detection rate of adverse reactions after more than two vaccinations was 73.08%,which was higher than the first vaccination detection rate of 26.92%.The clinical manifestations of vaccine adverse reactions were mainly fever,redness,and induration,with detection rates of 39.42%,21.15%,and 18.27%,respectively.The detection rate of adverse reactions in children with special health conditions under the age of two was higher,accounting for 75.00%.The detection rate of adverse reactions within 24 hours after vaccination was higher,accounting for 62.50%.After timely symptomatic treatment and follow-up observation,all adverse reactions in children with special health conditions after vaccination recovered within 7 days.Conclusion Adverse reactions after vaccination in children with special health conditions in Kunming are predominantly mild.The detection rate of adverse reactions post-vaccination for pertussis,measles,mumps,and meningococcal A+C is notably high.Children under 2 years old with premature birth,allergy,and anemia are more likely to have adverse reactions after vaccination.These adverse reactions typically manifest within 24 hours post-vaccination and resolve within 7 days.
10.Relationship between LMAN2 expression in HR-positive breast cancer tissues and patient prognosis and its effect on proliferation and migration of MCF-7 cells
YAN Changjiao ; HUANG Meiling ; XIAO Jingjing ; LING Rui
Chinese Journal of Cancer Biotherapy 2024;31(1):47-53
[摘 要] 目的:探究甘露糖结合凝集素2(LMAN2)在激素受体(HR)阳性乳腺癌组织中的表达水平与乳腺癌患者预后的关系及其对MCF-7 细胞增殖和迁移的影响。方法:通过TCGA、Bc-GenExMiner、GEPIA和Kaplan-Meier Plotter数据库分析LMAN2在乳腺癌组织和正常乳腺组织中的差异性表达及其与患者预后的关系。采用小RNA干扰技术将si-LMAN2#1、si-LMAN2#2及si-NC转染至MCF-7细胞,将过表达LMAN载体(pc-LMAN)及空载体pcDNA3.1阴性对照(pc-NC)转染至MCF-7细胞,实验分为si-LMAN2#1、si-LMAN2#2、si-NC、pc-LMAN2和pc-NC组。通过qPCR和WB实验检测各组细胞中LMAN2 mRNA和蛋白的表达水平,CCK-8、克隆形成、Transwell迁移、WB等实验检测敲低和过表达LMAN 2对MCF-7细胞增殖、克隆形成、迁移及AKT信号通路相关蛋白表达的影响。结果:LMAN2在乳腺癌组织中的表达水平显著高于正常乳腺组织(P<0.001)。HR阳性乳腺癌组织中LMAN2表达水平显著高于HR阴性乳腺癌组织(P<0.001);LMAN2高表达与HR阳性乳腺癌患者不良预后有关联。敲低LMAN2可显著降低MCF-7细胞的增殖和迁移能力(P<0.01或P<0.001),过表达LMAN2可显著提高MCF-7细胞的增殖和迁移能力(均P<0.001)。敲低LMAN2组MCF-7细胞中PTEN和P21蛋白表达水平均显著升高,p-AKT蛋白表达水平显著降低(均P<0.01)。结论:LMAN2在乳腺癌组织和HR阳性乳腺癌组织中高表达,且与不良预后有关联。LMAN2高表达与MCF-7细胞增殖和迁移有关联,其作用机制可能涉及AKT信号通路。

Result Analysis
Print
Save
E-mail