1.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
2.Qualitative and Quantitative Analysis of Chemical Constituents in Gualou Niubangtang by UPLC-Q-TOF-MS/MS and HPLC
Yiyi ZHANG ; Jing YANG ; Yuqing CHENG ; Huimin GAO ; Jin QIN ; Li YAO ; Xiyang DU ; Raorao LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):179-187
ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents, providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem, ChemicalBook, and ChemSpider, combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography (HPLC). ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents, including 69 flavonoids, 36 terpenoids, 23 phenylpropanoids, 8 phenylethanoid glycosides, and 19 other types of constituents. In the established quantitative analysis method, the seven main constituents showed good linearity within their respective linear ranges. The precision, repeatability, stability, and spike recovery all met the required standards. The results showed that the content ranges of geniposide, liquiritin, hesperidin, arctiin, baicalin, oroxylin A-7-O-β-D-glucuronide, and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25, 1.20-7.64, 5.45-7.45, 22.97-33.51, 29.95-39.07, 2.58-4.80, and 6.56-9.31 mg·g-1, respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang, clarifying that its material basis is primarily composed of flavonoids, terpenoids, phenylethanoid glycosides, and phenylpropanoids. Furthermore, it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control, action mechanism, and clinical application of this formula.
3.Association between screen behaviors with overweight and obesity among children and adolescents
Chinese Journal of School Health 2026;47(4):486-489
Objective:
To investigate the prevalence of overweight and obesity among children and adolescents in Yangzhou City, and its association with screen behaviors, so as to provide scientific evidence for weight management among students.
Methods:
In May 2025, an electronic questionnaire survey was conducted among children and adolescents in Yangzhou City. A total of 3 722 participants were selected from grades 4 to 12 in 18 primary and secondary schools (108 classes) by using stratified cluster random sampling. The Chi square test was used to compare the differences in the detection rates of overweight and obesity among children and adolescents with 5 types of screen behaviors (watching TV, playing electronic games, scrolling short videos, screen based learning, electronic socializing) in different time groups each day (never, >0~<2 h, ≥2 h). Multivariate Logistic regression analysis was performed to examine the associations of five types of screen behaviors, presence of electronic devices in the bedroom, and screen use during meals on the weight status of children and adolescents.
Results:
The prevalence of overweight and obesity among children and adolescents was 37.3%. For all five types of screen behaviors, the differences in the distribution of overweight and obesity detection rates among children and adolescents across the three time spent categories were statistically significant ( χ 2=30.76- 70.78 , all P <0.01). After adjusting for confounding factors, multivariate Logistic regression analysis revealed that frequent or always using screens during meals( OR =1.63, 95% CI =1.14~2.31), playing video games ( OR =1.28, 95% CI =1.11-1.48), browsing short videos ( OR =1.29, 95% CI=1.09-1.54), and screen based learning ( OR =1.26, 95% CI =1.10-1.44) were significantly associated with overweight and obesity among children and adolescents (all P <0.05).
Conclusions
Excessive screen use is positively correlated with the incidence of overweight and obesity in children and adolescents. Targeted interventions on screen behaviors among children and adolescents are therefore warranted.
4.Incidence and determinants of posttraumatic stress disorder at three months following a road traffic accident
Luodong YANG ; Haohao LI ; Yao MENG ; Liang JIANG ; Min HU ; Guiqing ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):314-320
ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder (PTSD) three months after a traffic accident, and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week, and the hamilton anxiety rating scale (HAMA), the hamilton depression rating scale-24 (HAMD-24), the social support rating scale (SSRS), and the simplified coping style questionnaire (SCSQ) were administered. A 3-month follow-up was subsequently conducted, during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 (PCL-5). Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ2 test, as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals, 17 cases developed PTSD, with a higher proportion of females (70.59%). Between-group comparisons showed that, compared with the PTSD group, the non-PTSD group had higher scores for positive coping, objective support, and subjective support (P<0.05), and lower scores for negative coping, HAMA, HAMD, and PCL-5 (P<0.05). Correlation analysis indicated that female gender, negative coping, and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level (OR=1.715, 95% CI: 1.020-2.883, P=0.042) and negative coping (OR=1.590, 95% CI: 1.003-2.522, P=0.048) were risk factors for PTSD, whereas objective support (OR=0.646, 95% CI: 0.451-0.925, P=0.017) was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions, the total SSRS score and its subjective and objective support dimensions, as well as their combined use, all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female, with higher HAMA and HAMD scores after a motor vehicle accident, and those with lower social support and negative coping strategies, should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.
5.Isometric exercise reduces resting blood pressure:a meta-analysis of moderating factors and dose effects
Yang JIANG ; Hao PENG ; Yanping SONG ; Na YAO ; Yueyu SONG ; Xingxiao YIN ; Yanqi LI ; Qigang CHEN
Chinese Journal of Tissue Engineering Research 2026;30(4):975-986
OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95%CI=-9.22 to-6.80,P<0.01,I2=18.20%,low evidence grade)and diastolic blood pressure(MD=-3.46,95%CI=-4.64 to-2.28,P<0.01,I2=0%,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P<0.01)and diastolic blood pressure(P<0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P>0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95%HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.
6.Sanren Runchang Formula Regulates Brain-gut Axis to Treat IBS-C: A Randomized Controlled Trial
Teng LI ; Xinrong FAN ; He YAN ; Zhuozhi GONG ; Mengxi YAO ; Na YANG ; Yuhan WANG ; Huikai HU ; Wei WEI ; Tao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):154-161
ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome (IBS-C) by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and substance P (SP). MethodsA randomized controlled design was adopted, and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups (36 cases).The observation group received Sanren Runchang formula granules twice daily, and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale (IBS-SSS), IBS Quality of Life Scale (IBS-QOL), and Bristol Stool Form Scale (BSFS) were used to assess clinical symptoms, and bowel movement frequency was recorded. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT, VIP, and SP. ResultsThe total response rate in the observation group was 91.67% (33/36), which was higher than that (77.78%, 28/36) in the control group (χ2=4.50, P<0.05). After treatment, both groups showed increased defecation frequency and BSFS scores, decreased IBS-SSS total score, abdominal pain and bloating scores, IBS-QOL health anxiety, anxiety, food avoidance, and behavioral disorders scores, SAS and SDS scores, serum 5-HT and VIP levels, and increased SP levels (P<0.05, P<0.01). Moreover, the observation group showed more significant changes in the indicators above than the control group (P<0.05, P<0.01). The SP level showed no significant difference between the two groups. During the 4-week follow-up, the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group, and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients, with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP, suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However, its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.
7.The current status of international health communication research and its implications for China
Lingyan YANG ; Zihan YU ; Yueqiao ZHAO ; Zhenping LI ; Jianyi YAO ; Hao LI ; Yuhui ZHOU
Journal of Public Health and Preventive Medicine 2026;37(1):18-21
Objective To systematically review international research on health communication, and to provide valuable insights and reference for China's health communication research and practice. Methods This study included 693 articles published from January 2023 to April 2024 in two authoritative academic journals in the field of health communication, “Health Communication” and the “Journal of Health Communication”. A systematic review was conducted on the themes, theoretical foundations, research methods, and populations of international health communication research. Results The findings in this study revealed that international health communication research topics were diverse, with hotspots including social media, health information behavior, health misinformation, stigmatization, trust, and risk perception. The results showed that 34% of the articles were based on theoretical foundations, and 93.3% employed research methods, focusing on adolescents, parents, women, and other key populations. Conclusion Domestic health communication research can expand its perspective from “information transmission” to “social interaction”, innovate theories and methods from “single paradigm" to “multi-integration” and shift focus from a “mass perspective” to “targeted care” for the health of all populations. Domestic health communication practice can delve into the localization of social media health communication practices, the comprehensive management of health misinformation, and the critical application of new technologies.
8.A Review of Methods for Establishing and Evaluating Animal Models of Stroke
Yunrong YANG ; Wenyu WU ; Yue TAN ; Guofeng YAN ; Yao LI ; Jin LU
Laboratory Animal and Comparative Medicine 2026;46(1):94-106
Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.
9.Analysis of Blood-absorbed Components and Their Metabolic Differences of Xiebaisan in Normal and Chronic Bronchitis Mice Based on UPLC-Q-Exactive Orbitrap MS
Peng PENG ; Jiaxin LI ; Xinyue YANG ; Fangle LIU ; Chenchen ZHU ; Chaozhan LIN ; Yufeng YAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):219-227
ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan(XBS) in normal and chronic bronchitis (CB) mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group, the normal drug administration group, the CB group, the CB drug administration group and the dexamethasone group, with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin (OVA). The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS(13.2 g·kg-1) from the 21st day, and the dexamethasone group mice were simultaneously gavaged with dexamethasone (0.5 mg·kg-1) until the end of the 35th day of the experiment. Subsequently, serum samples were collected and evaluated for their efficacy, based on the pharmacological evaluation indicators, to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents, blood-absorbed components, and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently, Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1, CYP3A1, UGT1A1, and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites (including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites) of XBS were unambiguously identified in the serum of normal mice. Additionally, a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites (including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites) of XBS in the serum of CB mice. Among them, 27 prototype components were detected in both states, including 12 flavonoids, 2 alkaloids, 3 triterpenes, 4 organic acids, 3 amides, 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice; however, there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice, the levels of phase Ⅰ metabolites such as oxidation, reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 (P<0.05), CYP3A1 (P>0.05), UGT1A1 (P<0.01) and UGT1A6 (P<0.01) enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice, especially in oxidation, reduction, methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1, CYP3A1, UGT1A1 and UGT1A6 in the liver.
10.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.


Result Analysis
Print
Save
E-mail