1.Mechanism of action and clinical research progress of iguratimod in connective tissue diseases
Xiaorong YANG ; Shuhong ZHOU ; Lijiang GUO ; Ying CHEN ; Yingying JI ; Lijie XU
China Pharmacy 2024;35(5):629-634
As a new type of immunosuppressant,iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines, and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors,reduce the production and deposition of immune complexes in the body,and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin,Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand, and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway,tumor necrosis factor-α,interleukin-1,interleukin-6,matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue,and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis,and no obvious safety risks have been found.
2.Golgi Transport 1A Promotes Cell Proliferation and Metastasis of Papillary Thyroid Carcinoma
Shuhong KE ; Zhujun XU ; Yang ZHOU ; Chenghong ZHENG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):69-75
ObjectiveTo investigate the expression level of Golgi transport 1A (GOLT1A) in thyroid carcinoma and its effects on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of thyroid carcinoma cells. MethodsThe expression of GOLT1A in thyroid carcinoma was analyzed online by tumor immune estimation resource (TIMER), the University of Alabama at Birmingham cancer data analysis portal (UALCAN), gene expression profiling interactive analysis 2 (GEPIA2). The expression level of GOLT1A in thyroid carcinoma cells was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and western blot. Cell counting kit-8 (CCK-8) assay, colony formation assay, and transwell assay were used to detect the effects of GOLT1A expression on the proliferation, migration, and invasion of thyroid carcinoma cells. Western blot assay was used to detect the effect of GOLT1A on the expression of EMT-related genes including E-cadherin, vimentin, and N-cadherin. ResultsThe online analysis of GEPIA2, TIMER, and UALCAN showed that the expression of GOLT1A was higher in thyroid carcinoma than in normal tissues, and the expression of GOLT1A in thyroid carcinoma cells was significantly higher than in normal control cells. Knockdown of GOLT1A inhibited TPC1 cell proliferation, migration, and invasion. The expression of E-cadherin increased and the expressions of N-cadherin and vimentin decreased in GOLT1A knockdown TPC1 cells. Overexpression of GOLT1A promoted BCPAP cell proliferation, migration, and invasion. The expression of E-cadherin decreased and the expressions of N-cadherin and vimentin increased in GOLT1A overexpression BCPAP cells. ConclusionGOLT1A is highly expressed in thyroid carcinoma and can promote the proliferation, migration, and invasion of thyroid carcinoma cells.
3.Levels of serum FOXO1 and ATG7 in elderly patients with severe pneumonia and their relationship with short-term prognosis
Shuhong SHENG ; Jing XU ; Youhui FU
International Journal of Laboratory Medicine 2024;45(10):1218-1222
Objective To explore the levels of serum forkhead transcription factor 1(FOXO1)and autoph-agy-related gene 7(ATG7)in elderly patients with severe pneumonia and their relationship with short-term prognosis.Methods A total of 122 elderly patients with severe pneumonia admitted to the hospital from Au-gust 2020 to August 2022 were selected as the case group,and 105 elderly people who came to the hospital for physical examination during the same period were selected as the control group.The serum levels of FOXO1 and ATG7 were detected by enzyme-linked immunosorbent assay(ELISA).The patients were divided into the survival group(n=91)and the death group(n=31)according to whether they died within 28 days after the diagnosis of severe pneumonia.Receiver operating characteristic(ROC)curve was used to evaluate the predic-tive value of serum FOXO1 and ATG7 levels for short-term mortality in elderly patients with severe pneumo-nia.The influencing factors for short-term mortality in elderly patients with severe pneumonia were explored by multivariate Logistic regression analysis.Results The serum FOXO1 and ATG7 levels in the case group were higher than those in the control group,and the differences were statistically significant(t=7.615,29.591,P<0.05).The serum expression levels of FOXO1 and ATG7 in the death group were higher than those in the survival group,and the differences were statistically significant(t=10.029,9.399,P<0.05).The area under the curve(AUC)of serum FOXO1 and ATG7 for predicting short-term mortality in elderly pa-tients with severe pneumonia was 0.733(95%CI:0.673-0.799)and 0.826(95%CI:0.756-0.893),respec-tively,and the AUC of FOXO1 combined with ATG7 for predicting short-term mortality in elderly patients with severe pneumonia was 0.908(95%CI:0.862-0.949).FOXO1 and ATG7 were positively correlated with acute physiology chronic health evaluation(APACHE Ⅱ)score(r=0.693,0.627,P<0.05).The results of multivariate Logistic regression showed that APACHE Ⅱ score ≥22.56(OR=3.589,95%CI:1.714-7.515),FOXO1 ≥10.67 ng/mL(OR=2.529,95%CI:1.232-5.193),ATG7 ≥16.35 pg/mL(OR=2.875,95%CI:1.414-5.845)were risk factors for death in elderly patients with severe pneumonia(P<0.05).Con-clusion Serum levels of FOXO1 and ATG7 are significantly increased in elderly patients with severe pneumo-nia,and both could be used to evaluate the short-term prognosis of elderly patients with severe pneumonia.
4.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
5.Data quality analysis of regional health information platform of community medical institutions in Beijing
Zhao YANG ; Shuhong ZHU ; Jicheng LV ; Xizi ZHENG ; Miao HUI ; Lingyi XU ; Li YANG
Chinese Journal of Medical Science Research Management 2023;36(6):465-468
Objective:This study aims to analyze of the quality of diagnosis and treatment data of community medical institutions on the national health information platform in a district of Beijing from the perspective of scientific research informatization, to provide experience and reference for promoting the informatization construction of primary medical units and tapping the scientific research potential of the regional data platform.Methods:Based on the data backup database of the national health information platform in the region, the data quality was analyzed and evaluated mainly in three dimensions: integrity, integration, and consistency.Results:Through the construction of the national health information platform, the district successfully achieved the effective collection of diagnosis and treatment data from community medical institutions, covering the main data such as patients′ basic information, visit information, test information, prescription information, etc. However, the data collected so far were still insufficient in terms of data integration and consistency.Conclusions:A regional medical data center is suggested to construct to break down the barriers between data systems, conduct pre-structuring of diagnosis and treatment data, improve data integration and consistency, and at the same time, carry out effective scientific research prospective design to promote the effective transformation of clinical data to scientific research data.
6.Epidemiological characteristics of genital Chlamydia trachomatis infections in Shaoxing City from 2012 to 2021
Shuhong XU ; Xingren SHAN ; Qiaoling LU ; Haibin MENG ; Jiaq YU
Journal of Preventive Medicine 2023;35(2):148-151
Objective:
To investigate the epidemiological characteristics of genital Chlamydia trachomatis infections in Shaoxing City from 2012 to 2021, so as to provide the evidence for improving the control strategy of genital C. trachomatis infections.
Methods:
Data pertaining of patients with genital C. trachomatis infections in Shaoxing City from 2012 to 2021 were retrieved from Chinese Disease Prevention and Control Information System, and the incidence of genital C. trachomatis infections was calculated. The trends in incidence of genital C. trachomatis infections were analyzed using annual percent change (APC), and temporal, human and temporal distributions of genital C. trachomatis infections were descriptively analyzed.
Results:
A total of 18 235 cases with genital C. trachomatis infection were reported in Shaoxing City from 2012 to 2021, and the annual average incidence was 36.36/105. The incidence of genital C. trachomatis infections appeared a tendency towards a rise in Shaoxing City from 2012 to 2021 (APC=4.51%, t=2.663, P=0.029). The reported incidence of genital C. trachomatis infections was significantly higher among females than among males (60.46/105 vs. 12.50/105; χ2=7 935.467, P<0.001), and 76.04% infections (13 866 cases) occurred at ages of 20 to <40 years, while a high incidence rate of genital C. trachomatis infections was seen among patients at ages of 25 to <30 years (154.23/105). In addition, high incidence rates were seen in Keqiao District (57.93/105) and Yuecheng District (51.78/105).
Conclusions
The incidence of genital C. trachomatis infections appeared a tendency towards a rise in Shaoxing City from 2012 to 2021, and the infection predominately occurred among women and young individuals.
7.Clinical study of treating somatoform pain disorder with the combination of electroacupuncture and duloxetine
Yongsheng DONG ; Shuhong SUN ; Shuang XU ; Dongbo YU ; Wei LI ; Jue HONG
Journal of Acupuncture and Tuina Science 2023;21(3):210-216
Objective:To observe the clinical efficacy of treating somatoform pain disorder(SPD)with electroacupuncture(EA)at the Governor and Conception Vessel points plus duloxetine.Methods:Eighty-two SPD patients were randomly allocated to an observation group and a control group,with 41 cases in each group.The control group was intervened by oral administration of duloxetine hydrochloride enteric capsules at a dose of 60 mg per time once a day;based on the medication,the observation group received additional EA treatment by selecting points from the Governor and Conception Vessels.Clinical efficacy was evaluated after 8 weeks of treatments;changes in the scores of the short-form McGill pain questionnaire(SF-MPQ),self-report symptom inventory,symptom check list-90(SCL-90),Pittsburgh sleep quality index(PSQI),and generic quality of life inventory-74(GQOLI-74)were also compared.Results:After the intervention,the observation group surpassed the control group in comparing the total effective rate(P<0.05).The SF-MPQ score,SCL-90 somatization score,and PSQI score dropped notably in both groups after treatment,and the intra-group differences were statistically significant(P<0.05);the three scores were significantly lower in the observation group than in the control group(P<0.05).The GQOLI-74 score got an increase in each dimension in both groups after treatment,and the intra-group differences were also statistically significant(P<0.05);the GQOLI-74 dimension scores were all significantly higher in the observation group than in the control group(P<0.05).Conclusion:For patients with SPD,combining EA at the Governor and Conception Vessel points and duloxetine hydrochloride enteric capsules can markedly improve their clinical symptoms and quality of life.
8.Status of smoking and smoking cessation among patients withhypertension in Nanshan District
Xinxing ZHAO ; Changyi WANG ; Shuhong DAI ; Hong' ; en CHEN ; Shan XU ; Xiaofeng LIANG
Journal of Preventive Medicine 2022;34(5):449-455
Objective:
To investigate the prevalence of current smoking and smoking cessation, and identify the influencing factors among hypertensive patients in Nanshan District, Shenzhen City, so as to provide insights into smoking control among hypertensive patients.
Methods:
The demographic features, life style, status of smoking and smoking cessation in hypertensive patients were collected from 69 community health centers in Nanshan District from 2017 to 2019. The gender- and age-specific prevalence of smoking and smoking cessation was estimated among hypertensive patients, and the factors affecting hypertensive patients' smoking and smoking cessation were identified using a multivariable logistic regression model.
Results:
Totally 4 385 patients with hypertension were enrolled, with a mean age of (58.41±11.19) years, and the participants included 2 265 men (51.65%) and 2 120 women (48.35%). There were 724 current smokers, and the prevalence of current smoking was 16.51%, with 29.71% prevalence in males and 2.41% in females. There were 424 hypertensive patients quitting smoking, and the prevalence of smoking cessation was 36.93%, with 38.20% prevalence in males. Multivariable logistic regression analysis identified male ( OR=12.885, 95%CI: 9.567-17.354 ) and drinking ( OR=2.567, 95%CI: 2.118-3.111 ) as facilitating factors for current smoking among hypertensive patients, and increasing age (OR=0.723, 95%CI: 0.642-0.815) and high exercise frequency (OR=0.881, 95%CI: 0.817-0.950) as barrier factors, while male ( OR=7.309, 95%CI: 3.304-16.165), increasing age ( OR=1.381, 95%CI: 1.120-1.703 ), unmarried ( OR=1.819, 95%CI: 1.329-2.490 ), divorced ( OR=7.837, 95%CI: 1.254-48.975 ), retired ( OR=1.545, 95%CI: 1.095-2.180 ), unemployed (OR=1.801, 95%CI: 1.057-3.066), and high exercise frequency ( OR=1.221, 95%CI: 1.096-1.360 ) were identified as facilitating factors for smoking cessation among hypertensive patients and widowed ( OR=0.285, 95%CI: 0.089-0.906 ), high educational level ( OR=0.766, 95%CI: 0.619-0.949 ), and drinking ( OR=0.488, 95%CI: 0.368-0.647 ) as barrier factors.
Conclusions
The prevalence of smoking is lower, and the prevalence of smoking cessation is higher among hypertensive patients than among general populations in Nanshan District. Young and middle-aged, employed, widowed men with a high educational level are key populations for tobacco control, and alcohol consumption control and intensified exercises are important measures to reduce the prevalence of smoking and improve the prevalence of smoking cessation.
9.Influencing factors of smoking behaviors among residents in Nanshan District
Ji ZHANG ; Shuhong DAI ; Hong' ; en CHEN ; Shan XU ; Xiao DONG ; Changyi WANG
Journal of Preventive Medicine 2022;34(5):466-470
Objective:
To investigate the status and identify the influencing factors of smoking behaviors among residents in Nanshan District, Shenzhen City, so as to provide insights into tobacco control.
Methods:
Permanent residents at ages of more than 18 years were recruited from 17 communities in Nanshan District, Shenzhen City using the stratified multistage random sampling method from July to November, 2018. Participants' demographic features, smoking, smoking cessation and exposure to secondhand smoke were collected using the Individual Questionnaire for 2018 Chinese Adult Chronic Disease and Nutrition Surveillance. The factors affecting current smoking were identified using a multivariable logistic regression model.
Results:
Totally 1 700 questionnaires were allocated, and 1 625 valid questionnaires were recovered, with an effective recovery rate of 95.59%. The respondents included 714 men and 911 women, with a male to female ratio of 1∶1.27, and had a mean age of ( 45.13±13.59 ) years. The prevalence of current smoking was 15.51%, with 28.15% prevalence in men and 5.60% in women. The mean age of starting daily smoke was ( 21.00±5.52 ) years, and the mean daily smoking frequency was (13.53±9.15) cigarettes/d. The prevalence of smoking cessation was 6.58%, with 10.64% in men and 3.40% in women, and the prevalence of exposure to secondhand smoke was 41.42%, including 46.63% in men and 37.32% in women. Multivariable logistic regression analysis showed that an educational level of junior high school ( OR=1.683, 95%CI: 1.088-2.602 ), an educational level of high school/technical secondary school/vocational school (OR=1.687, 95%CI: 1.185-2.402), an occupation of farmers ( OR=2.514, 95%CI: 1.404-4.500 ), and an occupation of commercial and service personnel ( OR=1.939, 95%CI: 1.093-3.439 ) were associated with current smoking.
Conclusion
The prevalence of current smoking is low among residents in Nanshan District, but the prevalence of current smoking in women is higher than the national level. Educational level and occupation are main factors affecting current smoking.
10.Efficacy evaluation of apatinib in first-line and maintenance therapy of extensive small-cell lung cancer
Jing LIU ; Shuli XU ; Hongying YAO ; Guorui SUN ; Qichao WANG ; Shuhong TANG
Chinese Journal of Postgraduates of Medicine 2022;45(7):628-632
Objective:To observe the efficacy of apatinib combined with first-line chemotherapy and maintenance therapy of only apatinib in patients with extensive small-cell lung cancer.Methods:The clinical data of 56 newly diagnosed patients with extensive small-cell lung cancer in the Fifth People′s Hospital of Dalian City from January 2018 to June 2019 were retrospectively analyzed. Among them, 27 patients (experimental group) were treated with first-line chemotherapy combined with apatinib, and 29 patients (control group) were treated with first-line chemotherapy alone. In experimental group, the expression levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 1 day before chemotherapy and 1 day after chemotherapy were detected by enzyme linked immunosorbent assay method. Response evaluation criteria in solid tumor (RECIST) was used to evaluate the efficacy. The occurrence of adverse reaction was recorded. The patients were followed up for 12 to 24 months, and progression-free survival and 1-year survival were recorded.Results:The objective response rate, median progression-free survival time and 1-year survival rate in experimental group were significantly higher than those in control group: 81.5% (22/27) vs. 55.2% (16/29), 10.5 months vs. 8.5 months and 81.5% (22/27) vs. 55.2% (16/29), and there were statistical differences ( P<0.05); there was no statistical difference in disease control rate between 2 groups ( P>0.05). In experimental group, the patients with complete response and partial response after chemotherapy were classified as effective subgroup (22 cases), and the patients with stationary disease and progressive disease were classified as ineffective subgroup (5 cases). There were no statistical difference in VEGF and VEGFR-2 before chemotherapy between 2 subgroups ( P>0.05). The VEGF and VEGFR-2 in effective subgroup were significantly lower than those in ineffective subgroup: (275.34 ± 16.15) ng/L vs. (330.24 ± 23.21) ng/L and (89.35 ± 4.34) ng/L vs. (112.34 ± 5.45) ng/L, and there were statistical differences ( P<0.01). There were no uncontrollable adverse reactions in 2 groups, and there was no statistical difference in the incidence of adverse reactions between 2 groups ( P>0.05). Conclusions:Application of apatinib in first-line therapy and maintenance therapy for patients with extensive small-cell lung cancer can improve clinical efficacy and survival benefit with controllable adverse reactions.


Result Analysis
Print
Save
E-mail