1.Salidroside alleviates PM2.5-induced pulmonary fibrosis through PINK1/Parkin
Ruixi ZHOU ; Wenbo WU ; Limin ZHANG ; Meina WU ; Chen LIU ; Siqi LI ; Xiaohong LI ; Mengxiao LUAN ; Qin WANG ; Li YU ; Yumei LIU ; Wanwei LI
Journal of Environmental and Occupational Medicine 2025;42(10):1240-1246
Background Existing studies have confirmed that fine particulate matter (PM2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg−1 by gavage, n=10), PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 + saline by gavage, n=10), and Sal + PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 +Sal 60 mg·kg−1 by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.
2.Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5
Siqi LI ; Chen LIU ; Weihong XU ; Wenbo WU ; Ruixi ZHOU ; Limin ZHANG ; Chao SONG ; Yumei LIU ; Fengjiao TAN ; Mengxiao LUAN ; Xiaolin HAN ; Jinfeng TAN ; Li YU ; Dongqun XU ; Qin WANG ; Xiaohong LI ; Wanwei LI
Journal of Environmental and Occupational Medicine 2024;41(2):125-132
Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.
3.Effect of vitamin C on intestinal flora disorders in Cr(VI)-contaminated mice
Limin ZHANG ; Chen LIU ; Yumei LIU ; Xueqian WU ; Ming SHU ; Jian ZHOU ; Dongqun XU ; Qin WANG ; Wanwei LI ; Xiaohong LI
Journal of Environmental and Occupational Medicine 2024;41(7):807-813
Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K2Cr2O7, Cr(VI)], and VC+K2Cr2O7 [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K2Cr2O7 solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K2Cr2O7 solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg−1, and the dose of K2Cr2O7 was 1.25 mg·kg−1. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.
4.Effect of Dihuang Yinzi Decoction (地黄饮子)on Retinal Insulin Content and Insulin Signaling Pathway Related Protein Expression in Alzheimer's Disease Model Mice
Dongyan WU ; Wanwei GUI ; Xiaodan WANG ; Qinqing LI ; Jinmiao CHAI ; Junlong ZHANG
Journal of Traditional Chinese Medicine 2024;65(15):1593-1601
ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction (地黄饮子) for improving cognitive dysfunction in Alzheimer's disease (AD) from the perspective of retina. MethodsForty-five APP/PS1 mice (AD model mice) were randomly divided into model group, Dihuang Yinzi Decoction group, and memantine group, with 15 mice in each group, while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/(kg·d) by gavage, mice in the memantine group were given memantine hydrochloride 6.1 mg/(kg·d) by gavage, and mice in the blank group and the model group were given normal saline 2 ml/(kg·d) by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed; Morris water maze was used to detect the changes in spatial memory ability of mice; glucose oxidase method was used to detect retinal glucose content of mice; enzyme-linked immunosorbent assay (ELISA) was used to detect serum and retinal insulin content of mice, and Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the retina, and the retinal thickness and ganglion cell number were counted; protein immunoblotting was performed to detect the retinal pathway-associated proteins [insulin receptor substrate 1 (IRS1), phosphorylated insulin receptor substrate 1 (pIRS1), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase B (Akt1), phosphorylated protein kinase B (pAkt1)] expression; retinal glucose transporter protein 4 (GLUT4) expression was detected by immunohistochemistry. ResultsCompared with the blank group, fasting blood glucose of mice in the model group at weeks 1, 2, 3, and 4, blood glucose and area under the curve (AUC) at different time point of OGTT and ITT test, fasting serum insulin, and HOMA-IR increased (P<0.05, P<0.01); in the Morris water maze experiment, the escape latency increased from day 3 to day 5, and the number of crossing platforms, the percentage of target quadrant distance, and the percentage of target quadrant time decreased (P<0.05, P<0.01); the outer nuclear layer of the retina became sparse, thinner, and the number of ganglion cells decreases (P<0.01); the expression level of retinal glucose increased, while the expression levels of insulin, pIRS1/IRS1, PI3K/β-Actin, pAkt1/Akt1, and GLUT4 proteins decreased (P<0.01). Compared with the model group, fasting blood glucose at week 4, blood glucose at each time point of the OGTT and ITT tests AUC decreased (P<0.05, P<0.01), and fasting serum insulin and HOMA-IR decreased (P<0.05) in Dihuang Yinzi Decoction group; In the Morris water maze test, the escape latency shortened on day 4 and day 5, number of platform crossings, target quadrant distance as a proportion of total distance, and target quadrant movement time as a proportion of total time decreased (P<0.05, P<0.01); retinal pathological changes alleviated, and retinal thickness and ganglion cell number increased (P<0.01); retinal glucose content decreased, and retinal pIRS1/IRS1, PI3K/β-Actin, and GLUT4 protein expression elevated (P<0.05 or P<0.01). ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease, which may be related to regulating retinal insulin content and insulin signaling pathway.
5.Protective effect of oleanolic acid on liver injury induced by acute exposure to mercury chloride and its possible mechanism
Chuan OUYANG ; Xuan MA ; Jiali ZHAO ; Yumei LIU ; Hongyang KE ; Qinghua LI ; Xiaohong LI ; Wanwei LI
Journal of Environmental and Occupational Medicine 2022;39(11):1298-1303
Background Acute exposure to mercury chloride (HgCl2) can cause liver damage. Whether oleanolic acid (OA) as a hepatoprotective drug can protect against liver injury induced by acute exposure to HgCl2 and related mechanism of action remain unclear. Objective To investigate the protective effect and possible mechanism of OA on liver injury in mice caused by acute exposure to HgCl2. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups with 10 mice in each group according to body weight. The four groups were named control group, OA group (300 mg·kg−1), HgCl2 group (5 mg·kg−1), and OA + HgCl2 group (300 mg·kg−1 OA + 5mg·kg−1 Hgcl2). Soybean oil and OA solution were administered intragastric once a day for two consecutive days. HgCl2 solution was injected intraperitoneally 2 h after the second intragastric administration. Mice were sacrificed after 48 h, and their serum and liver were collected. Liver coefficient was calculated. The changes of liver structure and iron deposition were observed by hematoxylin-eosin (HE) staining and Prussian blue staining. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total superoxide dismutase (T-SOD), reduced glutathione (GSH), malondialdehyde (MDA), and tissue iron content were measured with commercial kits. Western blotting was used to detect nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (Gpx4), transferrin receptor 1 (TFR1,) and solute carrier family 7 member 11 (SLC7A11). Results The AST and ALT levels of the HgCl2 group were (76.447±9.695) U·g−1 and (98.563±24.673)U·g−1, respectively, which were higher than those of the control group (P<0.05). After the OA pretreatment, the liver coefficient and the above indexes were decreased to (4.769±0.237)%, (57.086±10.087) U·g−1, and (87.294±27.181)U·g−1, respectively. The liver coefficient and AST level of the OA + HgCl2 group were significantly different from those of the HgCl2 group (P<0.05). After acute exposure to HgCl2, the hepatocytes of mice were disordered, accompanied by inflammatory infiltration, positive blue particles appeared in Prussian blue staining of liver tissue, and the above changes in liver tissue were alleviated after the OA pretreatment. The iron content in the HgCl2 group was (3.646±0.238) μmol·g−1, which was higher than that in the control group, (2.948±0.308) μmol·g−1. After the OA pretreatment, the iron content decreased to (3.429±0.415) μmol·g−1. Compared with the control group, acute exposure to HgCl2 resulted in decreased levels of GSH and T-SOD, decreased protein expression levels of Nrf2, HO-1, SLC7A11, and Gpx4, increased level of MDA, and increased protein expression level of TFR1 (P<0.05). After the OA pretreatment, all indicators were improved including increased GSH level, decreased MDA level, increased Nrf2, HO-1, and SLC7A11 protein expression levels, and decreased TFR1 protein expression level; compared with the HgCl2 group, the differences were statistically significant (P<0.05). Conclusion Acute HgCl2 exposure could induce liver injury in mice, and its mechanism may involve iron overload and ferroptosis. OA may alleviate the liver injury caused by acute HgCl2 exposure by affecting iron overload and the ferroptosis-related protein expression.
6.Assessment of demand for rehabilitation services and analysis of causes of the gap between supply and demand in China
Yiran WANG ; Wanwei DAI ; Binbin SU ; Huiyun FAN ; Jianjun LI ; Xiaoying ZHENG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(6):725-729
ObjectiveTo evaluate the overall demand for rehabilitation services from the perspective of the groups with disabilities, diseases, injuries and older adults, and explore the causes of the supply and demand gap of rehabilitation services. MethodsThe literatures in the field of rehabilitation were collected, summarized and analyzed, including policy documents issued by World Health Organization and relevant departments in China, surveys, and researches. ResultsThe demand for rehabilitation services caused by disabilities, chronic diseases, injuries and population ageing were vast in China, but many were still unmet. The main reasons leading to the gap included those population trend and health situation, the insufficient reserve of rehabilitation resources coming from incomplete development of rehabilitation service system early, and inadequate construction of disability reporting system, which could not efficiently meet rehabilitation demand with supply. ConclusionThe strategies to optimize the rehabilitation services system and promote the quality of the services based on the disability reporting system are warranted.
7.Fertility intension and concern of young breast cancer patients from the perspective of need theory: a qualitative study
Na LI ; Wanwei HUANG ; Lijuan ZHANG ; Yue ZHANG ; Yue LI
Chinese Journal of Modern Nursing 2021;27(25):3390-3396
Objective:To explore the feelings and experiences of young breast cancer patients' fertility intension and concern from the perspective of need theory, pay attention to the fertility needs of young breast cancer patients, so as to provide a basis for making personalized clinical decision and support.Methods:From April to July 2020, purpose sampling was used to select 12 young breast cancer patients from the Sun Yat-sen University Cancer Center for semi-structured interviews. The Colaizzi 7-step analysis method was used to encode, classify, and refine topics.Results:This study drew up an interview outline based on the need theory. This study conducted interviews with young breast cancer patients to extract 4 levels of themes related to the feelings and experiences of the fertility intension and concern, which were the basic needs and fertility concerns under the self-efficacy theory, and fertility intension and concern at the level of need for belonging and love, and self-realization needs and fertility concerns based on the sublimation of social roles, and fertility choice and concerns under the background of traditional culture.Conclusions:From the perspective of need theory, role realization and traditional culture have obvious influences on young breast cancer patients' fertility intension and concern. When making diagnosis, treatment and nursing decisions, medical and nursing staff need to give personalized fertility information support and nursing guidance based on the patient's social and cultural background.
8.Scientific publication management during the public health pandemic: Case analysis of the studies involving COVID-19 pregnant women
Can LIU ; Yaqin LEI ; Jiayun LI ; Changsi ZOU ; Tianyu CAO ; Wanwei DAI
Chinese Journal of Medical Science Research Management 2021;34(4):278-283
Objective:Based on the analysis of case report and case series studies involving COVID-19 pregnant women in China, we aimed to discuss the updated management requirements for publication of scientific papers at hospitals in the new circumstances and context.Methods:The case report and case series studies published by domestic scholars in the early stage of COVID-19 outbreak were retrieved. Bibliometrics were used to analyze the research time, research content and research objects of the included literatures.Results:Nearly 200 cases (55%) of the 360 cases of COVID-19 pregnant women could not be clearly excluded from the possibility of repeated reporting. However, all these cases were not disclosed in the paper for possible repeated report.Conclusions:Potential repeated report problem may cause trouble for later meta-analysis, which also may have negative impact for the development of clinical guidelines. The departments of scientific research management at hospital should pay more attention to the management of patient′s data in scientific papers, so that it can better serve the accurate assessment of disease characteristics and epidemic situation, as well as the scientific formulation of clinical guidelines and control strategies.
9.Analysis on the influencing factors of individual academic performance based on the construction of research hospital: Taking Peking University Third Hospital as an example
Wanwei DAI ; Jiayun LI ; Liyuan TAO ; Chun ZHANG
Chinese Journal of Medical Science Research Management 2021;34(4):292-296
Objective:This paper aim to analyze the influencing factors of individual academic performance based on the construction of a research-oriented hospital, to provide possible reference for improving the service of science and technology management.Methods:Selecting 45 experts determine the constituent index and assign value of the academic performance evaluation system by using Delphi method. The index setting emphasized clinical application orientation, and weighted total score was used as the academic performance evaluation standard. Conduct a-350-person anonymous questionnaire survey and use descriptive analysis and multiple logistic regression methods to analyze the influencing factors.Results:The system includes a total number of 6 first-level indicators and 43 second-level indicators. The authoritative coefficients of the consulting experts are 8.5±0.6, and the Kendall of the two rounds of consultation are 0.78 and 0.83( P<0.05). The questionnaire results show that respondents with Ph. D degree, senior professional titles, mentor qualification, from large team and higher scientific research service support have better academic performance. personal background, team support and scientific research services have significant impact on academic performance. Conclusions:In order to improve the scientific research strength of the hospital, it is significant to focus on systematic scientific research training, strengthening discipline teams and research platforms, and improving the professional level of scientific research management.
10. Relationship between radon exposure and oxidative damage in solar greenhouse workers
China Occupational Medicine 2018;45(03):312-315
OBJECTIVE: To understand the relationship between radon exposure and oxidative damage in solar greenhouse employees.METHODS: A total of 216 solar greenhouse employees were selected as the study subjects by using cluster random sampling method.Radon concentrations in solar greenhouses were detected by using continuous radon measuring instrument,which were used to estimate the annual radon radiation dose in solar greenhouse employees.T-superoxide dismutase( T-SOD) and malondialdehyde( MDA) levels in venous blood were measured,which were used to present the oxidative damage effects in solar greenhouse employees.RESULTS: The annual radon radiation dose of solar greenhouse employees was 2.00 mSv in 2014.T-SOD activity was( 87.43 ± 15.77) × 10~3 U/L,and MDA concentration was( 4.36 ±0.62) μmol/L.Multivariate logistic regression analysis results showed that after excluding confounding factors such as gender,age,smoking,alcohol drinking,planting length and pesticide exposure score,the higher the radon exposure dose,the higher risk of abnormalities in T-SOD activity and MDA concentration( P < 0.05).CONCLUSION: There is a correlation between radon exposure and oxidative damage effects in solar greenhouse employees.

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