1.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
;
Percutaneous Coronary Intervention/methods*
;
Male
;
Female
;
Coronary Artery Disease/drug therapy*
;
Retrospective Studies
;
Renal Dialysis/methods*
;
Middle Aged
;
Aged
;
China
;
Proportional Hazards Models
;
Treatment Outcome
2.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
3.Efficacy of modified electroconvulsive therapy combined with medication in inpatient schizophrenia patients and urban-rural differences
Hongcheng XIE ; Shuangshuang FENG ; Tingting WANG ; Junfan LIANG ; Jiajun REN ; Hongli ZHANG ; Ziyuan LIN ; Siru WANG ; Bo XIANG ; Kezhi LIU
Sichuan Mental Health 2024;37(6):497-501
BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy (MECT) is currently a commonly used method for treating schizophrenia, but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments, so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center, Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022, who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ,were included in the study. Patients were divided into two groups: medication-only group (n=106) and MECT combined with medication group (n=481). In MECT combined with medication group, 24 rural patients residing in urban areas were excluded, leaving the remaining patients divided into urban group (n=103) and rural group (n=354) based on their place of residence. Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate, and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score, positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant (F=11.149, 12.111, 31.725, χ2=14.010, P<0.01). Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group (F=3.946, 4.523, χ2=4.033, P<0.05). ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia, and the combined therapy may be more effective in urban patients than that in rural patients, with potentially more pronounced improvements in positive symptoms.
4.Correlation between sleep midpoint and sleep quality in type 2 diabetic patients with insomnia
Lingling ZHAO ; Wei XIE ; Huaqian DONG ; Xiuya REN ; Qing LIU ; Dan YUAN ; Yiming XIANG ; Liyuan LUO ; Yihan ZHOU
Chinese Journal of Practical Nursing 2023;39(31):2419-2425
Objective:To analyze the correlation between sleep midpoint and sleep quality in insomnia patients with type 2 diabetes mellitus (T2DM).Methods:By adopting current situation investigation research, total of 150 T2DM patients hospitalized in the Department of Endocrinology, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from November 2021 to July 2022 were selected as the research objects. The general information questionnaire, Pittsburgh Sleep Quality Index (PSQI), anxiety scale (SAS) and Depression Scale (SDS) were used to investigate, and then analysis the datum.Results:Among 150 T2DM insomnia patients, 41 cases (27.33%) were in the early midpoint sleep group, 37 cases (24.67%) were in the middle midpoint sleep group, and 72 cases (48.00%) were in the late midpoint sleep group. There were significant differences in the distribution of sex, age and BMI level among different sleep midpoint groups ( χ2=7.24, 13.36, 15.93, all P<0.05). The scores of time to fall asleep at the midpoint of sleep in the 3 groups were (2.12 ± 1.25), (2.65 ± 0.79), (2.33 ± 1.02), the difference was significant ( F=2.14, P<0.05); the daytime disability scores in the 3 groups were (1.39 ± 1.36), (2.16 ± 1.12), (1.85 ± 1.32), the difference was significant ( F=3.17, P<0.05). Logistic regression analysis of disorder showed that the time to fall asleep ( OR=4.922, P<0.05) and daytime disability ( OR=4.043, P<0.05) had significant influence to the middle midpoint of sleep group when the early midpoint of sleep group as the control, while the male ( OR=2.182, P<0.05), 50 - 70 years old ( OR=5.005, P<0.05) and BMI over fat side ( OR=3.488, P<0.05) had significant influence to the late midpoint of sleep group. Conclusions:Medical staff should pay attention to the sleep quality of T2DM patients, pay attention to the sleep midpoint of patients, and improve patients′cognition of healthy sleep patterns.
5. The inhibitory effect of Averrhoa carambola DMDD on high glucose-induced endoplasmic reticulum stress IRE1α pathway and inflammation in renal tubular epithelial cell HK-2
Yu-Xiang WANG ; Jing-Xiao XIE ; Xiao-Ping ZHANG ; Chuan-Hao PANG ; Lu WANG ; Qiu-Yan CHEN ; Lin-Qian CHEN ; Ren-Bin HUANG ; Xiao-Jie WEI
Chinese Pharmacological Bulletin 2023;39(7):1270-1275
Aim To investigate the inhibition effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-l, 4-dione ( DMDD) on renal tubular epithelial cell HK-2 endo¬plasmic reticulum stress and inflammatory responses induced by high glucose. Methods HK-2 cells were cultured in vitro and divided into normal group, high glucose group, endoplasmic reticulum stress inhibitor 4-PBA group (5 mmoL • L ) , DMDD high, medium and low dose groups (8,4,2 μmol • L
6.Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023)
Yang LI ; Yuchang WANG ; Haiwen PENG ; Xijie DONG ; Guodong LIU ; Wei WANG ; Hong YAN ; Fan YANG ; Ding LIU ; Huidan JING ; Yu XIE ; Manli TANG ; Xian CHEN ; Wei GAO ; Qingshan GUO ; Zhaohui TANG ; Hao TANG ; Bingling HE ; Qingxiang MAO ; Zhen WANG ; Xiangjun BAI ; Daqing CHEN ; Haiming CHEN ; Min DAO ; Dingyuan DU ; Haoyu FENG ; Ke FENG ; Xiang GAO ; Wubing HE ; Peiyang HU ; Xi HU ; Gang HUANG ; Guangbin HUANG ; Wei JIANG ; Hongxu JIN ; Laifa KONG ; He LI ; Lianxin LI ; Xiangmin LI ; Xinzhi LI ; Yifei LI ; Zilong LI ; Huimin LIU ; Changjian LIU ; Xiaogang MA ; Chunqiu PAN ; Xiaohua PAN ; Lei PENG ; Jifu QU ; Qiangui REN ; Xiguang SANG ; Biao SHAO ; Yin SHEN ; Mingwei SUN ; Fang WANG ; Juan WANG ; Jun WANG ; Wenlou WANG ; Zhihua WANG ; Xu WU ; Renju XIAO ; Yang XIE ; Feng XU ; Xinwen YANG ; Yuetao YANG ; Yongkun YAO ; Changlin YIN ; Yigang YU ; Ke ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Gang ZHAO ; Xiaogang ZHAO ; Xiaosong ZHU ; Yan′an ZHU ; Changju ZHU ; Zhanfei LI ; Lianyang ZHANG
Chinese Journal of Trauma 2023;39(2):97-106
During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.
7.Diagnosis and treatment strategy of penoscrotal avulsion injury based on AAST penoscrotal injury grade
Xiang WAN ; Xiaomin REN ; Dachao ZHENG ; Minkai XIE ; Jianshu NI ; Zhong WANG ; Bin XU ; Haijun YAO
Journal of Modern Urology 2023;28(7):573-575
【Objective】 To explore the emergency treatment of penoscrotal avulsion injury based on the American Association for Surgery and Trauma (AAST) penoscrotal injury grade. 【Methods】 Data of 30 patients with penoscrotal avulsion injury treated in our hospital with in-situ suture, skin grafting or skin flap during Oct.2003 and Dec.2017 were reviewed. 【Results】 Among the 30 patients, 29 received emergency surgery, including in-situ suturein 15 grade Ⅰ-Ⅲ cases, skin graft in 8 grade Ⅳ-Ⅴ cases, and skin flap in 6 cases;1 case received delayed operation due to wound infection on admission. In the perioperative period,25 cases had more than 90% wound healing, 3 cases had 70% wound healing after wound dressing change, and 2 cases had complete necrosis. Second-stage skin graft yielded satisfactory penoscrotal appearance. 【Conclusion】 According to the specific conditions of patients, reasonable surgical methods can be selected. For grade Ⅰ-Ⅲ patients, in-situ suture can be used, while for grade Ⅳ-Ⅴ patients, wound condition, age, fertility and other factors should be taken into consideration so as to preserve the function of testis to the maximum extent.
8.SBC (Sanhuang Xiexin Tang combined with Baihu Tang plus Cangzhu) alleviates NAFLD by enhancing mitochondrial biogenesis and ameliorating inflammation in obese patients and mice.
Zhitao REN ; Gemin XIAO ; Yixin CHEN ; Linli WANG ; Xiaoxin XIANG ; Yi YANG ; Siying WEN ; Zhiyong XIE ; Wenhui LUO ; Guowei LI ; Wenhua ZHENG ; Xiaoxian QIAN ; Rihan HAI ; Liansheng YANG ; Yanhua ZHU ; Mengyin CAI ; Yinong YE ; Guojun SHI ; Yanming CHEN
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):830-841
In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans
;
Mice
;
Animals
;
Non-alcoholic Fatty Liver Disease/metabolism*
;
NF-kappa B/metabolism*
;
Organelle Biogenesis
;
Retrospective Studies
;
Mice, Inbred C57BL
;
Obesity/metabolism*
;
Liver
;
Inflammation/metabolism*
;
Body Weight
;
Lipid Metabolism
;
Lipids
;
Diet, High-Fat/adverse effects*
9.Status of HVPG clinical application in China in 2021
Wen ZHANG ; Fuquan LIU ; Linpeng ZHANG ; Huiguo DING ; Yuzheng ZHUGE ; Jitao WANG ; Lei LI ; Guangchuan WANG ; Hao WU ; Hui LI ; Guohong CAO ; Xuefeng LU ; Derun KONG ; Lin SUN ; Wei WU ; Junhui SUN ; Jiangtao LIU ; He ZHU ; Dongliang LI ; Wuhua GUO ; Hui XUE ; Yu WANG ; Jiancuo GENGZANG ; Tian ZHAO ; Min YUAN ; Shirong LIU ; Hui HUAN ; Meng NIU ; Xin LI ; Jun MA ; Qingliang ZHU ; Wenbo GUO ; Kunpeng ZHANG ; Xiaoliang ZHU ; Birun HUANG ; Jianan LI ; Weidong WANG ; Hongfeng YI ; Qi ZHANG ; Long GAO ; Guo ZHANG ; Zhongwei ZHAO ; Kai XIONG ; Zexin WANG ; Hong SHAN ; Mingsheng LI ; Xueqiang ZHANG ; Haibin SHI ; Xiaogang HU ; Kangshun ZHU ; Zhanguo ZHANG ; Hong JIANG ; Jianbo ZHAO ; Mingsheng HUANG ; Wenyong SHEN ; Lin ZHANG ; Feng XIE ; Zhiwei LI ; Changlong HOU ; Shengjuan HU ; Jianwei LU ; Xudong CUI ; Ting LU ; Shaoqi YANG ; Wei LIU ; Junping SHI ; Yanming LEI ; Jinlun BAO ; Tao WANG ; Weixin REN ; Xiaoli ZHU ; Yong WANG ; Lei YU ; Qiang YU ; Huiling XIANG ; Wenqiang LUO ; Xiaolong QI
Chinese Journal of Hepatology 2022;30(6):637-643
Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
10.Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis.
Xiang Hong YAN ; Jia Ling WU ; Rong YU ; Xiao Hua MA ; Qing Fu LI ; Ren Feng XIE
Chinese Journal of Preventive Medicine 2022;56(2):185-191
To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.
Carcinoma, Hepatocellular/genetics*
;
Case-Control Studies
;
Genetic Predisposition to Disease
;
Genotype
;
Hepatitis B virus/genetics*
;
Hepatitis B, Chronic/genetics*
;
Humans
;
Liver Cirrhosis/genetics*
;
Liver Neoplasms/genetics*
;
Polymorphism, Single Nucleotide
;
STAT3 Transcription Factor/genetics*

Result Analysis
Print
Save
E-mail