1.Gene-predicted associations between 731 immune cell phenotypes and rheumatoid arthritis
Fengzhi LIU ; Yuna DONG ; Wenyi TIAN ; Chunlei WANG ; Xiaodong LIANG ; Lin BAO
Chinese Journal of Tissue Engineering Research 2026;30(5):1311-1319
BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.
2.Concentrations characteristics of common air pollutants and health risk assessment of practitioners in hair and beauty salons in Shanghai, 2016–2024
Jiao CHEN ; Tian CHEN ; Xiaoyu WANG ; Yewen SHI ; Fengchan HAN ; Yi HE ; Xiaodong SUN ; Xianliang WANG
Journal of Environmental and Occupational Medicine 2026;43(3):326-332
Background As common public facilities essential to daily life, hair and beauty salons frequently contain various airborne toxic and hazardous pollutants potentially leading to adverse health effects for salon practitioners. Objective To characterize the indoor air pollution profiles of common contaminants in hair and beauty salons in Shanghai and to evaluate the associated health risks for practitioners, in order to provide a scientific basis for strengthening the public health management in Shanghai and protecting the health of practitioners. Methods The air quality monitoring data of hair and beauty salons in Shanghai from 2016 to 2024 were obtained from the “Health Hazard Factors Monitoring Program for Public Places” of the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention. Monitoring indicators included particulate matter ≤10 μm in aerodynamic diameter (PM10), particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), formaldehyde, ammonia, benzene, toluene, and xylene. Indicator compliance rates were calculated across various years in accordance with GB 9666-1996 Hygienic standard for barber shop and beauty shop and GB 37488-2019 Hygiene indicators and limit for public places; specifically, PM2.5 was assessed against the limits stipulated in GB/T 18883-2022 Standards for indoor air quality. A questionnaire survey was conducted among salon practitioners to collect weekly working days and daily working hours. The non-carcinogenic risks associated with inhalation exposure to formaldehyde, ammonia, benzene, toluene, and xylene as well as the carcinogenic risks posed by formaldehyde and benzene were evaluated following WS/T 777-2021 Technical guide for environmental health risk assessment of chemical exposure and the U.S. Environmental Protection Agency inhalation risk model. Results The overall compliance rates of PM10, formaldehyde, ammonia, benzene, and toluene in the air of hair and beauty salons in Shanghai from 2016 to 2024 were 92.13%, 96.59%, 96.15%, 94.93%, and 94.97%, respectively; the overall compliance rate of xylene was a little lower (85.92%), and the overall compliance rate of PM2.5 was 57.18%. The P50 concentrations of PM10, PM2.5, formaldehyde, ammonia, benzene, toluene, and xylene did not exceed the corresponding limits. The P50 of non-carcinogenic risk indicator (hazard quotient, HQ) for formaldehyde, ammonia, benzene, toluene, and xylene were <1. The probabilities of non-carcinogenic risk HQ >1 for formaldehyde and xylene were 41.4% and 10.9%, respectively, which were higher than that of other pollutants. The P50 of carcinogenic risk (CR) for formaldehyde and benzene were between 1.0×10−6 and 1.0×10−4, while the probabilities of CR >1.0×10−4 were 16.9% and 14.0%, respectively. Conclusion The overall compliance rate of common pollutant concentrations in the air of hair and beauty salons in Shanghai is high, and the hygienic condition meets the requirements of national standards. The non-carcinogenic health risks posed by formaldehyde and xylene to employees (with formaldehyde being more prominent), as well as the carcinogenic risks associated with formaldehyde and benzene, deserve heightened attention in future health supervision.
3.Gene-predicted associations between 731 immune cell phenotypes and rheumatoid arthritis
Fengzhi LIU ; Yuna DONG ; Wenyi TIAN ; Chunlei WANG ; Xiaodong LIANG ; Lin BAO
Chinese Journal of Tissue Engineering Research 2026;30(5):1311-1319
BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.
4.Efficacy and safety of using an enteral immunonutrition formula in the enhanced recovery after surgery protocol for Chinese patients with gastrointestinal cancers undergoing surgery: A randomized, open-label, multicenter trial (healing trial).
Jianchun YU ; Gang XIAO ; Yanbing ZHOU ; Yingjiang YE ; Han LIANG ; Guole LIN ; Qi AN ; Xiaodong LIU ; Bin LIANG ; Baogui WANG ; Weiming KANG ; Tao YU ; Yulong TIAN ; Chao WANG ; Xiaona WANG
Chinese Medical Journal 2025;138(21):2847-2849
5.Effect of different bone grafting methods and internal fixation on mechanical stability of Schatzker type Ⅱ tibial plateau fracture.
Zhongzheng WANG ; Yuchuan WANG ; Siyu TIAN ; Zitao WANG ; Ruipeng ZHANG ; Xiaodong LIAN ; Zhanle ZHENG ; Yingze ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):807-813
OBJECTIVE:
To investigate the biomechanical characteristics of Schatzker type Ⅱ tibial plateau fracture fixed by different bone grafting methods and internal fixations.
METHODS:
Twenty-four embalmed specimens of adult knee joint were selected to make Schatzker type Ⅱ tibial plateau fracture models, which were randomly divided into 8 groups (groups A1-D1 and groups A2-D2, n=3). After all the fracture models were restored, non-structural iliac crest bone grafts were implanted in group A1-D1, and structural iliac crest bone grafts in groups A2-D2. Following bone grafting, group A was fixed with a lateral golf locking plate, group B was fixed with lateral golf locking plate combined compression bolt, group C was fixed with lateral tibial "L"-shaped locking plate, and group D was fixed with lateral tibial "L"-shaped locking plate combined compression bolt. Compression and cyclic loading tests were performed on a biomechanical testing machine. A distal femur specimen or a 4-cm-diameter homemade bone cement ball were used as a pressure application mould for each group of models. The specimens were loaded with local compression at a rate of 10 N/s and the mechanical loads were recorded when the vertical displacement of the split bone block reached 2 mm. Then, compressive and cyclic loading tests were conducted on the fixed models of each group. The specimens were compression loaded to 100, 400, 700, and 1 000 N at a speed of 10 N/s to record the vertical displacement of the split bone block. The specimens were also subjected to cyclic loading at 5 Hz and 10 N/s within the ranges 100-300, 100-500, 100-700, and 100-1 000 N to record the vertical displacement of the split bone block at the end of the entire cyclic loading test. The specimens were subjected to cyclic loading tests and the vertical displacement of the split bone block was recorded at the end of the test.
RESULTS:
When the vertical displacement of the collapsed bone block reached 2 mm, the mechanical load of groups A2-D2 was significantly greater than that of groups A1-D1 ( P<0.05). The mechanical load of groups B and D was significantly greater than that of group A under the two bone grafting methods ( P<0.05); the local mechanical load of group D was significantly greater than that of groups B and C under the structural iliac crest bone grafts ( P<0.05). There was no significant difference ( P>0.05) in the vertical displacement of the split bone blocks between the two bone graft methods when the compressive load was 100, 400, 700 N and the cyclic load was 100-300, 100-500, 100-700 N in groups A-D. However, the vertical displacement of bone block in groups A1-D1 was significantly greater than that in groups A2-D2 ( P<0.05) when the compressive loading was 1 000 N and the cyclic load was 100-1 000 N. The vertical displacement of bone block in group B was significantly smaller than that in group A, and that in group D was significantly smaller than that in group C under the same way of bone graft ( P<0.05).
CONCLUSION
Compared with non-structural iliac crest bone grafts implantation, structural iliac crest bone grafts is more effective in preventing secondary collapse of Schatzker type Ⅱ tibial plateau fracture, and locking plate combined with compression bolt fixation can provide better articular surface support and resistance to axial compression, and the lateral tibial "L"-shaped locking plate can better highlight its advantages of "raft" fixation and show better mechanical stability.
Humans
;
Bone Transplantation/methods*
;
Tibial Fractures/physiopathology*
;
Fracture Fixation, Internal/instrumentation*
;
Biomechanical Phenomena
;
Bone Plates
;
Ilium/transplantation*
;
Adult
;
Tibia/surgery*
;
Bone Cements
;
Knee Joint/surgery*
;
Male
;
Tibial Plateau Fractures
6.Cedrol regulates radiosensitivity of prostate cancer cells through cGAS-STING signal pathway mediated immune escape
Xiu TIAN ; Xiaodong LAI ; Xiaohui JIA ; Yanchun GUO ; Lin LONG
Chinese Journal of Immunology 2025;41(1):100-106
Objective:To investigate effect of cedrol on radiosensitivity of prostate cancer(PCa)cells and its mechanism.Methods:mRNA and protein expressions of cGAS and STING in PCa tissues and cells were detected by qRT-PCR and Western blot,respectively.Human PCa cells PC-3 were divided into control group,radiation group,cedrol group,combination group and inhibitor group.Radiosensitivity of cells in each group was detected by plate cloning test;apoptosis,migration and invasion were detected by flow cytometry,scratch test and Transwell chamber,respectively;γ-H2AX immunofluorescence staining was used to analyze effect of cedrol on DNA damage repair;after PC-3 cells and CD8+T cells were co-cultured,cells were divided into T cell group,co-culture group,cedrol group and inhibitor group,MTT and flow cytometry were used to detect proliferation and apoptosis of CD8+T cells,IFN-γ,IL-2 and TNF-α levels in supernatant of CD8+T cells were detected by ELISA;Western blot was used to detect prolife-rating cell nuclear antigen(PCNA),Bcl-2 associated protein(Bax),programmed death recepter ligand 1(PD-L1)and cGAS-STING signal pathway protein.Results:cGAS and STING protein and mRNA expressions in PCa tissues and cells were decreased(P<0.05),which were lowest in PC-3 cells.Compared with control group,colony formation rate,cell survival rate,scratch healing rate and cell inva-sion rate of PC-3 cells in radiation group and cedrol group were decreased obviously,apoptosis rate and number of γ-H2AX focus were increased obviously(P<0.05);compared with radiation group and cedrol group,combined group inhibited proliferation,migration and invasion of PC-3 cells,and induced DNA damage and apoptosis(P<0.05);inhibitor group attenuated inhibitory effect of com-bined group on proliferation,migration and invasion of PC-3 cells,and promoted DNA damage and apoptosis(P<0.05);compared with T cell group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in co-culture group were decreased,apoptosis rate was in-creased(P<0.05);compared with co-culture group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in cedrol group were in-creased,apoptosis rate was decreased(P<0.05);compared with cedrol group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in inhibitor group were decreased,apoptosis rate was increased(P<0.05).Compared with control group,expressions of PCNA and PD-L1 proteins in PC-3 cells in cedrol group were reduced obviously,expressions of Bax,cGAS and STING proteins were increased obviously(P<0.05);inhibitors of cGAS-STING pathway could reverse effect of cedrol on above proteins(P<0.05).Conclusion:Cedrol may enhance radiosensitivity of PCa cells by activating cGAS-STING signal pathway and inhibiting immune escape.
7.Practical exploration on the responsibilities and operation specifications of assistants in robotic radical gastrectomy
Yulong TIAN ; Yuqi SUN ; Xiaoning KANG ; Yan WANG ; Shougen CAO ; Xiaodong LIU ; Zequn LI ; Gan LIU ; Xiaojie TAN ; Cheng MENG ; Haitao JIANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Gastrointestinal Surgery 2025;28(8):937-941
Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.
8.Research progress on risk factors and treatment of thromboembolism caused by Mycoplasma pneumoniae infection in children
Xiaofei TIAN ; Xiaodong WANG ; Kaining SHEN
Chinese Pediatric Emergency Medicine 2025;32(11):858-862
The risk factors for thromboembolism caused by Mycoplasma pneumoniae infection include severe Mycoplasma pneumoniae pneumonia,elevated D-dimer levels,abnormal inflammatory markers,platelet abnormalities,lung consolidation,lung necrosis and pleural effusion,and so on.In terms of treatment,tetracycline and quinolone antibiotics have shown new advantages in addressing the recent prevalence of macrolide resistant mycoplasma.Regarding anticoagulant therapy,direct oral anticoagulants represented by rivaroxaban have significant advantages and are safe in children's medication.In addition,the application of traditional Chinese medicine for promoting blood circulation and removing blood stasis needs to be developed.The identification and intervention of risk factors related to coagulation disorders and thromboembolism caused by Mycoplasma pneumoniae infection can help improve treatment effectiveness.
9.Analysis of completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer : a national multicenter real-world study
Kexuan LI ; Tixian XIAO ; Xiaodong WANG ; Bin WU ; Guole LIN ; Yuchen GUO ; Ming QU ; Si WU ; Xiaodong YANG ; Yinshengbo′er BAO ; Baohua WANG ; Fan ZHANG ; Xiangwang YU ; Beizhan NIU ; Junyang LU ; Lai XU ; Guannan ZHANG ; Zhen SUN ; Guoyou ZHANG ; Yan SHI ; Hong JIANG ; Yongjing TIAN ; Yongxiang LI ; Hongwei YAO ; Jun XUE ; Quan WANG ; Lie YANG ; Qian LIU ; Yi XIAO
Chinese Journal of Digestive Surgery 2025;24(1):113-119
Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.
10.Prognosis and risk factors of different recurrence and metastasis patterns following pancreatectomy
Bohan YANG ; Kai CHEN ; Lizhi XU ; Hongyu SHEN ; Anqi GUO ; Yishuo LIU ; Yongsu MA ; Xiaodong TIAN ; Yinmo YANG
Chinese Journal of Surgery 2025;63(8):704-711
Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

Result Analysis
Print
Save
E-mail