1.Study on the immunotoxicity and mechanism of Carthamus tinctorius extract on RBL-2H3 cells
Silan WU ; Xiaoli MEI ; Jinping LUO ; Li ZHANG ; Sixing HUANG ; Chonggang HUANG
China Pharmacy 2026;37(8):1003-1008
OBJECTIVE To investigate the immunotoxicity and potential mechanism of Carthamus tinctorius extract on RBL-2H3 cells via direct induction and induction by sensitized serum prepared with an overdose of the extract. METHODS For direct induction by C. tinctorius extract, RBL-2H3 cells were divided into normal control group (no treatment) and C. tinctorius extract group (10 mg/mL). For induction by sensitized serum prepared with an overdose of C. tinctorius extract, rats were divided into normal control group (no treatment), adjuvant-treated group (1 mL adjuvant), C. tinctorius extract-induced sensitization group (2.04 g/mL), and ovalbumin (OVA)-induced sensitization group (50 mg/mL). Sensitization was performed once every other day for a total of 3 times. Morphological changes of RBL-2H3 cells were observed, the degranulated rate of cells was counted, and histamine content was determined; the release rate of β -hexosaminidase ( β -Hex) was calculated, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and intracellular Ca²⁺ concentration were detected. RESULTS Under direct induction by C. tinctorius extract, compared with the normal control group, the volume of cells in the C. tinctorius extract group was significantly reduced and cell density decreased; the degranulation rate of cells, histamine content, β -Hex release rate, IL-6 and TNF-α levels, as well as intracellular Ca²⁺ concentration were all significantly increased ( P <0.01). Under i nduction by sensitized serum prepared with an overdose of C. tinctorius extract, compared with the adjuvant-treated group, the above indicators in the C. tinctorius extract-induced sensitization group and the OVA-induced sensitization group showed consistent changes with those in the C. tinctorius extract group under direct induction, all being significantly elevated ( P <0.01). CONCLUSIONS C. tinctorius extract may affect degranulation of RBL-2H3 cells and promote Ca²⁺ influx accompanied by the release of pro-inflammatory cytokines through two approaches: direct induction and induction by sensitized serum prepared under overdose administration. Its mechanism may be related to the activation of the calcium signaling pathway and the regulation of inflammatory pathways under the synergistic effect of multiple components.
2.Impact of early detection and management of emotional distress on length of stay in non-psychiatric inpatients: A retrospective hospital-based cohort study.
Wanjun GUO ; Huiyao WANG ; Wei DENG ; Zaiquan DONG ; Yang LIU ; Shanxia LUO ; Jianying YU ; Xia HUANG ; Yuezhu CHEN ; Jialu YE ; Jinping SONG ; Yan JIANG ; Dajiang LI ; Wen WANG ; Xin SUN ; Weihong KUANG ; Changjian QIU ; Nansheng CHENG ; Weimin LI ; Wei ZHANG ; Yansong LIU ; Zhen TANG ; Xiangdong DU ; Andrew J GREENSHAW ; Lan ZHANG ; Tao LI
Chinese Medical Journal 2025;138(22):2974-2983
BACKGROUND:
While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients.
METHODS:
This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively.
RESULTS:
The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge.
CONCLUSION
Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans
;
Retrospective Studies
;
Male
;
Length of Stay/statistics & numerical data*
;
Female
;
Middle Aged
;
Adult
;
Psychological Distress
;
Inpatients/psychology*
;
Aged
;
Anxiety/diagnosis*
;
Depression/diagnosis*
3.Efficacy and safety of secukinumab in Chinese patients with psoriasis: Update of six-year real-world data and a meta-analysis.
He HUANG ; Yaohua ZHANG ; Caihong ZHU ; Zhengwei ZHU ; Yujun SHENG ; Min LI ; Huayang TANG ; Jinping GAO ; Dawei DUAN ; Hequn HUANG ; Weiran LI ; Tingting ZHU ; Yantao DING ; Wenjun WANG ; Yang LI ; Xianfa TANG ; Liangdan SUN ; Yanhua LIANG ; Xuejun ZHANG ; Yong CUI ; Bo ZHANG
Chinese Medical Journal 2025;138(23):3198-3200
4.Analysis of the correlation between blood lipid levels and cognitive dysfunction in elderly people aged 65 and above
Jinping HUANG ; Yuanzheng FU ; Yangjian PAN ; Yurong HU ; Jinquan ZHANG ; Xiaoyan DU
Chinese Journal of Preventive Medicine 2025;59(7):1084-1089
his cross-sectional study employed convenience sampling to enroll 1 994 community-dwelling older adults (aged ≥65 years) undergoing health examinations at a Guangzhou community hospital between January and December 2024, aiming to investigate associations between blood lipid profiles and cognitive impairment. Cognitive function was assessed using the AD8 scale, with demographic characteristics (age, sex, education, occupation), health status (hypertension, diabetes mellitus), and lifestyle factors (smoking/alcohol use) collected via questionnaires. Fasting blood samples quantified triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Propensity score matching (PSM) balanced baseline characteristics between lipid-level groups. Pre-PSM analyses revealed significant intergroup differences: TG groups differed in sex, BMI, alcohol use, hypertension, and self-rated health ( P<0.05); TC groups in sex, age, occupation, diabetes, and hypertension; LDL-C groups in sex, age, occupation, diabetes, hypertension, and daily living ability; HDL-C groups in sex, age, education, occupation, BMI, smoking, diabetes, and hypertension. Post-PSM adjustment eliminated baseline differences ( P>0.05). Multivariable logistic regression adjusted for demographic, clinical, and lifestyle factors demonstrated that elevated TG levels conferred a 48% reduced risk of cognitive dysfunction [ OR (95% CI): 0.52 (0.29-0.94)], whereas TC, LDL-C, and HDL-C showed no significant associations (all P>0.05). These findings suggest an inverse association between higher triglyceride levels and cognitive dysfunction risk in older adults, highlighting TG′s potential protective role in cognitive health.
5.HIV-1 pretreatment drug resistance and molecular transmission network characteristics in Yubei District,Chongqing
Difei LI ; Ying XU ; Mao YE ; Xin HUANG ; Xuemei MA ; Yi JIN ; Songsong SUN ; Jinping XIONG ; Hui LIU ; Guohui WU
Chongqing Medicine 2025;54(3):719-724,730
Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.
6.Biejiajian Pill inhibits the malignant biological behavior of Hep3B cells through CMTM6
Yinfan LI ; Junjie XU ; Tao LAN ; Yufeng LI ; Xin LI ; Ronghua ZHANG ; Jinping HUANG ; Lihua ZHU ; Guangling ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):522-531
Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P>0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P<0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P<0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P<0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.
7.Expression of TRM cells in the lesions of imiquimod-induced models of psoriasis in mice
Yuchan ZHOU ; Rongchang ZHENG ; Huarun LI ; Jinping HUANG ; Si QIN ; Ting LI ; Zhenyu LU ; Sihui LI ; Xianwen LI ; Mu-jin LI ; Ju WEN
The Journal of Practical Medicine 2025;41(9):1327-1331
Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5%imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.
8.Biejiajian Pill inhibits the malignant biological behavior of Hep3B cells through CMTM6
Yinfan LI ; Junjie XU ; Tao LAN ; Yufeng LI ; Xin LI ; Ronghua ZHANG ; Jinping HUANG ; Lihua ZHU ; Guangling ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):522-531
Objective To investigate the effect of Biejiajian Pill(BJJP)on malignant biological behavior of hepatocellular carcinoma Hep3B cells and its regulatory mechanism.Methods A total of 72 healthy SD rats were randomly divided into blank control(BC)group,low(0.55 g/kg),medium(1.10 g/kg)and high(2.20 g/kg)BJJP experimental group,and drug-containing serum was prepared.Hep3B cells were divided into BC group,normal rat serum treatment(NC)group,low dose BJJP(LBJJP)group,medium dose BJJP(MBJJP)group and high dose BJJP(HBJJP)group,empty plasmid(pcDNA3.1)group,and CKLF-like MARVEL transmembrane domain containing 6(CMTM6)overexpression(pcDNA3.1-CMTM6)group,and the NC+pcDNA3.1 group,MBJJP+pcDNA3.1 group,NC+pcDNA3.1-CMTM6 group and MBJJP+pcDNA3.1-CMTM6 group.The proliferation of hepatoma Hep3B cells was detected by CCK-8.The migration and invasion of hepatoma Hep3B cells were detected by Transwell assay.The expression levels of proliferation-related proteins proliferating cell nuclear antigen(PCNA),epithelial-mesenchymal transition(EMT)related proteins(E-cadherin,N-cadherin and Vimentin),and CMTM6 proteins in hepatoma Hep3B cells were detected by Western blotting experiments.Results Compared with those in BC group,there were no significant differences in the proliferation,migration and invasion abilities of Hep3B cells,or the expression levels of PCNA,EMT related proteins(E-cadherin,N-cadherin and Vimentin)and CMTM6 protein in NC group(P>0.05).Compared with NC group,LBJJP,MBJJP and HBJJP drug-containing serum inhibited the proliferation,migration and invasion of Hep3B cells,downregulated the protein expression of PCNA;MBJJP and HBJJP upregulated the protein expression of E-cadherin.The protein expressions of N-cadherin,Vimentin and CMTM6 were downregulated,with significant differences(P<0.05).Compared with pcDNA3.1 group,the protein expression of CMTM6,cell proliferation,migration,invasion,PCNA protein expression,N-cadherin protein expression,and Vimentin protein expression in Hep3B cells in pcDNA3.1-CMTM6 group were significantly upregulated,while the protein expression of E-cadherin was significantly downregulated(P<0.05).Compared with NC+pcDNA3.1 group,the proliferation,migration and invasion abilities of Hep3B cells in MBJJP+pcDNA3.1 group were decreased,the expression levels of PCNA,Vimentin and N-cadherin protein were decreased,while the expression level of E-cadherin protein was increased.Compared with NC+pcDNA3.1-CMTM6 group,MBJJP+pcDNA3.1-CMTM6 group had the same results in the proliferation,migration and invasion abilities of Hep3B cells and the protein expression levels of PCNA,Vimentin,N-cadherin and E-cadherin.The differences were statistically significant(all P<0.05).Conclusion BJJP may inhibit the proliferation,migration,invasion and EMT of hepatoma Hep3B cells by regulating the expression of CMTM6.
9.Analysis of the correlation between blood lipid levels and cognitive dysfunction in elderly people aged 65 and above
Jinping HUANG ; Yuanzheng FU ; Yangjian PAN ; Yurong HU ; Jinquan ZHANG ; Xiaoyan DU
Chinese Journal of Preventive Medicine 2025;59(7):1084-1089
his cross-sectional study employed convenience sampling to enroll 1 994 community-dwelling older adults (aged ≥65 years) undergoing health examinations at a Guangzhou community hospital between January and December 2024, aiming to investigate associations between blood lipid profiles and cognitive impairment. Cognitive function was assessed using the AD8 scale, with demographic characteristics (age, sex, education, occupation), health status (hypertension, diabetes mellitus), and lifestyle factors (smoking/alcohol use) collected via questionnaires. Fasting blood samples quantified triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Propensity score matching (PSM) balanced baseline characteristics between lipid-level groups. Pre-PSM analyses revealed significant intergroup differences: TG groups differed in sex, BMI, alcohol use, hypertension, and self-rated health ( P<0.05); TC groups in sex, age, occupation, diabetes, and hypertension; LDL-C groups in sex, age, occupation, diabetes, hypertension, and daily living ability; HDL-C groups in sex, age, education, occupation, BMI, smoking, diabetes, and hypertension. Post-PSM adjustment eliminated baseline differences ( P>0.05). Multivariable logistic regression adjusted for demographic, clinical, and lifestyle factors demonstrated that elevated TG levels conferred a 48% reduced risk of cognitive dysfunction [ OR (95% CI): 0.52 (0.29-0.94)], whereas TC, LDL-C, and HDL-C showed no significant associations (all P>0.05). These findings suggest an inverse association between higher triglyceride levels and cognitive dysfunction risk in older adults, highlighting TG′s potential protective role in cognitive health.
10.Expression of TRM cells in the lesions of imiquimod-induced models of psoriasis in mice
Yuchan ZHOU ; Rongchang ZHENG ; Huarun LI ; Jinping HUANG ; Si QIN ; Ting LI ; Zhenyu LU ; Sihui LI ; Xianwen LI ; Mu-jin LI ; Ju WEN
The Journal of Practical Medicine 2025;41(9):1327-1331
Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5%imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Result Analysis
Print
Save
E-mail