1.Prevalence and associated factors of work-related musculoskeletal disorders among workers in a manganese enterprise
Tianzi SHAN ; Junxiang MA ; Tian CHEN ; Kang NONG ; Yucheng SUN ; Xueting WANG ; Gaoman ZHANG ; Teng MA ; Zhuoran XIA ; Fengtao CUI ; Li CHEN ; Yanyan ZHENG ; Piye NIU
Journal of Environmental and Occupational Medicine 2026;43(3):333-340
Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ2 test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.
2.Effect of Jianpi Qinghua Granules on Blood Glucose Fluctuations and Skeletal Muscle Mass and Function in Newly Diagnosed Overweight/Obese Type 2 Diabetes Patients with Qi-Yin Deficiency Syndrome
Yuan CHEN ; Qiuyue GUO ; Yanyan XIAO ; Hao LU ; Chi CHEN ; Junfei XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):218-224
ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus (T2DM) and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function, while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized, double-blind, placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine (TCM) group (54 cases) or the control group (56 cases). Patients in the TCM group received Jianpi Qinghua Granules, while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention, blood glucose fluctuations were assessed using the following parameters: time in the target blood glucose range (TIR), mean daily blood glucose (MBG), standard deviation of mean daily blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), coefficient of variation of blood glucose (CV), glycated hemoglobin (HbA1c) achievement rate, fasting plasma glucose (FPG), and 2 hour postprandial glucose (2 hPG). Skeletal muscle mass was measured by dual-energy X-ray absorptiometry (DXA), while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally, pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention, ensuring comparability. After treatment, compared to the control group, the TCM group showed a significant increase in TIR (P<0.01). While the SDBG and CV decreased, and MBG and MAGE increased in the TCM group, these differences were not statistically significant. Notably, the TCM group exhibited significant reductions in 2 hPG (P<0.01) and HbA1c (P<0.05), though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group (χ2=45.498, P<0.01). In terms of skeletal muscle mass and function, the TCM group demonstrated a significant increase in handgrip strength (P<0.01) and a significant reduction in the 5-time sit-to-stand duration (P<0.05). However, although body fat percentage increased, leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat, these changes were not statistically significant. For pancreatic islet function, the TCM group showed significant reductions in fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) (P<0.01). Additionally, the TCM syndrome score in the TCM group was significantly reduced (P<0.01). ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function, improving pancreatic islet function, and ameliorating related TCM syndromes.
3.Effect of virtual reality biofeedback training combined with oral positioning therapy on dysphagia after oral cancer surgery
Mingxia XU ; Hui ZHU ; Piaopiao CHEN ; Kexin MENG ; Jie CHEN ; Jing CHEN ; Huifang SUN ; Yanyan SUN
Chinese Journal of Rehabilitation Theory and Practice 2026;32(4):445-452
ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η2p = 0.641) and time (F = 230.870, P < 0.001, η2p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η2p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η2p = 0.415) and time (F = 89.464, P < 0.001, η2p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η2p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η2p = 0.283) and time (F = 49.650, P < 0.001, η2p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η2p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.
4.Determination of multi-component content and analysis of differential components in Aurantii Fructus Immaturus from different origins
Qianying WU ; Dehong LIU ; Weikang CHEN ; Xi CHEN ; Yanyan ZHU ; Jie WANG
China Pharmacy 2025;36(9):1071-1075
OBJECTIVE To determine the contents of 15 components in Aurantii Fructus Immaturus from different origins (Citrus aurantium, C. junos, C. aurantium Linn., C. sinensis Osb., C. sinensis), screen differential components, and provide references for the quality evaluation of Aurantii Fructus Immaturus. METHODS HPLC method was adopted to determine the contents of synephrine, N-methyltyramine, 5,7-dihydroxychromone-7-neohesperidoside, neoponcirin, narirutin, naringin, hesperidin, neohesperidin, naringenin, hesperetin, sinensetin, nobiletin, tangeretin, 5-demethylnobiletin, and auraptene in 46 batches of Aurantii Fructus Immaturus from different origins. The determination was performed on Waters Symmetry C18 column with mobile phase consisted of acetonitrile-0.1% formic acid (gradient elution) at the flow rate of 1.0 mL/min; column temperature was set at 40 ℃ , detection wavelength was 284 nm, and sample injection volume was 5 μL. The differences between different origins of Aurantii Fructus Immaturus were analyzed by cluster analysis, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and differential components were screened. RESULTS The linear relationships of the aforementioned 15 components were all good within the tested mass concentration ranges (all r>0.999 0). The RSDs for precision, stability (24 h), and repeatability tests were all less than 2.00%. The average recovery rate ranged from 91.1% to 103.9% (all RSDs<3.10%). Cluster analysis, PCA, and OPLS-DA revealed that C. sinensis Osb. and C. sinensis were clustered into one category, while C. aurantium,C. junos and C. aurantium Linn. were clustered into another category. The variable importance projection values for neohesperidin, auraptene, naringin, neoponcirin, tangeretin, hesperidin, sinensetin, and 5,7-dihydroxychromone-7-neohesperidoside were all greater than 1. CONCLUSIONS In this study, the contents of 15 components in Aurantii Fructus Immaturus from different origins are determined, and 8 differential components, including neohesperidin, auraptene, naringin, and neoponcirin, are screened out.
5.Clinical application of gasless endoscopic thyroidectomy via posterior chest-collarbone approach in the treatment of papillary thyroid carcinoma
Lixiang LI ; Yanyan LIU ; Haohao CHEN ; Wencan YANG ; Xuwen HAO ; Rongsheng SU
Chinese Journal of Endocrine Surgery 2025;19(1):51-56
Objective:To investigate the clinical results of gasless endoscopic thyroidectomy via posterior chest-collarbone approach (GETPCA) compared with open neck surgery for papillary thyroid carcinoma (PTC) .Mthods:Retrospective analysis of PTC patients admitted to the Department of Thyroid and Breast Surgery of the Third Affiliated Hospital of Anhui Medical University from Jan. 2022 to Dec. 2023,and randomly divided into the open group and the lumbo-scopic group according to whether or not they had a requirement for an unmarked neck, in which the open group was n=100,and the lumbo-scopic group was n=67,with 39 male cases and 128 female cases. Clinicopathological characteristics, surgery-related indexes, postoperative complications, postoperative pain scores and postoperative cosmetic satisfaction were compared between the two groups.The t-test,Wilcoxon rank-sum test, χ2 test, consecutively corrected χ2 test, or Fisher’s exact probability method were used to compare the groups. Results:No recurrence was seen during the follow-up period,and none of the cases in the luminal group was open in the middle. The differences in age, body mass index BMI, gender, relative tumor location,preoperative TSH, T stage and N stage between the two groups were not statistically significant ( P>0.05) . The total operation time [ (121.07±39.80) min vs. (93.87±26.97) min]in the luminal group was greater than that in the open group,intraoperative bleeding was less than that in the open group, and the postoperative drainage flow[ (130.69±31.01) mL vs. (105.52±32.71) mL] was greater than that in the open group in the postoperative period of 72 h, and the difference was statistically significant ( P<0.001) .There was no statistical difference between the two groups in terms of 24-h postoperative drainage volume, number of central zone lymph node dissection, number of positive central zone lymph nodes,postoperative hospitalization days or total hospitalization cost ( P>0.05) .The number of cases of neck discomfort (3 cases vs.23 cases, P<0.001) and swallowing dysfunction (2 cases vs.20 cases, P=0.003) in the luminal group was smaller than that in the open group,and the difference was statistically significant.The difference in the incidence of bleeding,incision infection,seroma,temporary recurrent laryngeal nerve injury and temporary parathyroid gland injury between the two groups was also not statistically significant ( P>0.05) .The postoperative NRS on day 1 and postoperative NRS on day 3 of the luminal group were lower than those of the open group,and the difference was statistically significant ( P>0.05) ,while there was no statistically significant difference between the postoperative NRS on day 7,the postoperative NRS on month 1 and the postoperative NRS on month 3 ( P>0.05) .Cosmetic satisfaction at 6 months postoperatively was higher in the luminal group than in the open group,and the difference was statistically significant ( P<0.001) . Conclusion:GETPCA for the treatment of the PTC is safe and feasible,with satisfactory cosmetic results and reduction of neck discomfort and swallowing dysfunction,which is worthy of clinical popularization.
6.The postictal electroencephalographic characteristics and prognosis of status epilepticus
Honghua CHEN ; Lingli JU ; Yanyan JI ; Yiyang XUE ; Lihong TAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):990-996
Objective:To analyze postictal electroencephalographic(EEG) characteristics of patients with status epilepticus (SE) based on the score of grand total electroencephalography (GTE), and explore the relationship between electroencephalographic characteristics of SE and clinical prognosis.Methods:A total of 110 SE patients were enrolled in the Department of Neurology, the Affiliated Hospital of Yangzhou University from September 1, 2021 to September 1, 2023. EEG and GTE scores were performed in all patients after seizures (0-2 days after the cessation of SE). After one year of discharge, the medication and seizure status of patients were followed up by phone or outpatient visits. The seizure outcomes were recorded according to the international league against epilepsy (ILAE) seizure outcome classification, with favorable outcomes defined as good prognosis group ( n=54) and unfavorable outcomes defined as poor prognosis group ( n=56). SPSS 27.0 software was used for statistical analysis. Binary Logistic regression analysis was employed to screen impact variables of prognosis. The receiver operating characteristic(ROC) curve was plotted to determine the optimal cut-off point for predicting prognosis in epilepsy. Results:There were statistically significant differences in the total GTE score(2(1, 4), 8(5, 10); Z=-6.837, P<0.001), diffuse slow activity(0(0, 1), 2(0, 2); Z=-6.495, P<0.001), reactivity of the rhythmic background activity(0(0, 0), 0(0, 1); Z=-2.705, P=0.007), paroxysmal activity(0(0, 0), 1.5(0, 3.0); Z=-4.420, P<0.001), focal disturbances(0(0, 0), 0(0, 0); Z=-2.130, P=0.033), and sharp wave activity(0(0, 2), 2(2, 3); Z=-5.714, P<0.001)between the good prognosis group and poor prognosis group. The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity and total GTE score (all P<0.05). The differences in EEG results between SE patients with clear and unknown causes were statistically significant in terms of paroxysmal activity and focal disturbances(both P<0.05). The results of binary Logistic regression analysis showed that independent factors associated with the prognosis of SE included medication adherence ( B=-0.496, OR=0.609, 95% CI=0.395-0.940, P=0.025), diffuse slow activity( B=1.580, OR=4.854, 95% CI=1.586-14.855, P=0.006), sharp wave activity( B=0.824, OR=2.280, 95% CI=1.210-4.297, P=0.011), and total GTE score ( B=0.561, OR=1.753, 95% CI=1.360-2.259, P<0.001). In evaluating the prognosis of SE, the GTE score had a certain sensitivity (74.6%) and specificity (85.1%), with a optimal cut-off point of 6. Conclusions:The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity. The appearance of diffuse slow activity and sharp wave activity in the electroencephalogram of SE patients indicates poor prognosis, and the total GTE score≥6 may be a strong predictor of poor prognosis. However, good medication adherence is a protective factor for epilepsy recurrence.
7.Cloning and expression of PPE65 encoded by the Mycobacterium tuberculosis Rv3621c gene in Escherichia coli,and its effects on proliferation and TGF-β expression of BEAS-2B cells
Juncheng HUANG ; Xinwen BO ; Jing LI ; Xuke CHEN ; Jiaxin ZHAO ; Yanyan ZHANG ; Xinwei FENG ; Yan SUN ; Zhengrong WANG ; Meng QI
Chinese Journal of Zoonoses 2025;41(10):1025-1033
This study was aimed at preliminarily investigating the molecular biological functions of the PPE65 protein from Myco-bacterium tuberculosis,and providing foundational data for tuberculosis prevention and control.The basic biological properties of the PPE65 gene-encoded protein were predicted with bioinformatics tools.Sequence information for the Mycobacterium tuberculosis Rv3621c gene and PPE65 protein was retrieved from the NCBI database.The Rv3621c gene was amplified through PCR with the H37Rv genome as a template,then cloned into the pET22b(+)expression vector.The recombinant pET22b(+)-PPE65 plasmid was transformed into Escherichia coli BL21(DE3)competent cells for IPTG-induced expression.Solubility analysis,purification,and identification of the recombinant PPE65 protein were performed.BEAS-2B cells were treated with various concentrations of PPE65 protein for 24 h,and cell proliferation was assessed with CCK-8 assays.PPE65 was found to be composed of 413 amino acids and to have a molecular formula of C????H????N???O???S??,a relative molecular mass of 40 679.88,a theoretical isoelectric point of 4.60,an ali-phatic index of 81.94,and an average hydrophilicity value of 0.319,thus indicating a stable hydrophobic protein lacking signal pep-tides or transmembrane domains.Secondary structure analysis revealed 53.03%α-helix(Hh),2.66%β-sheet(Ee),and 44.31%ran-dom coil(Cc).Bioinformatics predictions identified 38 B-cell epitopes and 22 CTL/Th-cell epitopes.The full-length PPE65 gene(1 308 bp)was confirmed through double restriction enzyme digestion and sequencing,thereby validating the correct construction of the pET22b(+)-PPE65 recombinant plasmid.SDS-PAGE analysis demonstrated that the recombinant protein was found in inclusion bodies,and a single band at 43.7 kDa was observed after purification.Western blotting revealed specific binding to mouse-derived His monoclonal antibodies,thereby confirming successful expression of the PPE65 protein.BEAS-2B cells treated with a PPE65 protein concentration gradient(2.5-20 μg/mL)exhibited a dose-dependent increase in cell number.Compared with those in the PBS control group,TGF-β relative expression levels were significantly higher in all treatment groups(t2.5=4.893,P<0.001,t5.0=4.640,P<0.05,t10=7.535,P<0.05,t20=16.44,P<0.000 1).This study elucidated the structural characteristics of the PPE65 protein,successfully obtained the recombinant protein through prokaryotic expression and purification,and demonstrated its ability to promote BEAS-2B cell proliferation.The underlying mechanism might involve suppression of TGF-β/S mad signaling pathway activation.These findings provide a theoretical basis for understanding the role and regulatory mechanisms of PPE65 during M.tuberculosis infection.
8.Non-drug intervention for nipple pain or injury in breastfeeding women:a summary of best evidence
Mengdi CAO ; Yanyan WANG ; Liangyi YAO ; Xin CHEN ; Jing LI ; Xing LI
Modern Clinical Nursing 2025;24(5):65-72
Objective To search,evaluate and summarise the best evidence on non-drug intervention for nipple pain or injury in breastfeeding mothers.Methods Based on the"6S pyramid"evidence model,desktop searches were conducted on databases of UpToDate,Joanna Briggs Institute evidence-based practice database(JBI),National Guideline Clearinghouse(NGC),National Institute for health and Care Excellence(NICE),Guidelines International Network(GIN),Registered Nurses'Association of Ontario(RNAO),American College of Obstetricians and Gynecologists(ACOG),Medlive,Chinese Medical Association(CMA)website,Breastfeeding Medical Association(BMA),CNKI,Wanfang Data,SinoMed,Cochrance Library,PubMed,Embase,Web of Science,and CINAHL for literature in non-drug interventions for nipple pain or injury in breastfeeding women.The literature included clinical guidelines,decisions,recommended practices,evidence summaries,expert consensus,systematic reviews and randomized controlled trials(RCTs).The searched databases spanned from 1st January,2013 to 30th April,2024.Two researchers who were trained in evidence-based nursing independently evaluated the methodological quality,extracted and integrated evidence from eligible literature.Results A total of 15 documents were included,consisting of 5 clinical guidelines,2 clinical decisions,1 expert consensus,6 systematic evaluations and 1 RCT.Thirty-one pieces of evidence were summarised across 4 categories:accurate perinatal assessment,feeding guidance,non-drug intervention and health education.Conclusion The summarised best evidence on non-drug intervention for nipple pain or injury in breastfeeding women provides an evidence-based basis for clinical healthcare professionals.
9.Screening and clinical characteristics of mutations in ABCC8 gene in pedigrees of maturity-onset diabetes of the young
Tiantian LI ; Yanyan JIANG ; Xiaoxu GE ; Ming LI ; Chanwei LIU ; Rong ZHANG ; Yating CHEN ; Fusong JIANG ; Limei LIU
Chinese Journal of Diabetes 2025;33(8):597-604
Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.
10.The effects of pepsin on the mucosal epithelium of the laryngopharynx under different pH condition
Yanyan ZHENG ; Donghui YAN ; Shiyan CHEN ; Hongxun GONG ; Xianming CHEN
Journal of Audiology and Speech Pathology 2025;33(2):161-165
Objective To investigate the damage of pepsin to the mucosal epithelium of the pharynx under a-cidic and non-acidic conditions,and to provide new ideas for the treatment of refractory laryngopharyngeal reflux diseases.Methods A total of 30 healthy guinea pigs were selected and randomly divided into 3 groups(with 10 in each group).The animals in group A were perfused with 0.3%pepsin+hydrochloric acid solution(pH=2),the animals in group B were perfused with 0.3%pepsin+sterilized distilled water(pH=7),and the animals in group C were perfused with sterilized distilled water(pH=7).After 14 days of perfusion,the mucosal tissues of the post-cyclic area were examined by HE staining,immunohistochemistry,and transmission electron microscopy to detect the degree of inflammatory cell infiltration,the expression of occludin and claudin-3 proteins,the degree of epithelial cell gap widening,and also to analyze the changes of cell submicroscopic structure under electron microscopy.Re-sults ① The submucosal leukocyte count was 28.61±7.10 in group A,29.89±7.04 in group B,and 7.81±1.40 in group C.Compared with group C,the leukocyte count was higher in group A and group B(P<0.05).② Com-pared with group C,both occludin and claudin-3 protein expression were downregulated in group A(P<0.05),compared with group C,the difference between occludin and claudin-3 protein expression in group B was not statisti-cally significant(P>0.05).③ Under electron microscopy,the mucosal epithelial cell gap was widened,the mito-chondria was swollen and the cristae was degraded in group A.In group B,there was no widening of the mucosal epithelial cell gap,but the mitochondria in the cytoplasm was swollen and the cristae was degraded,and there was no widening of mucosal epithelial cell gap and the morphological markers of mitochondria were clear in group C.Conclusion Under non-acidic conditions,pepsin still can cause inflammatory changes and mitochondrial damage in the mucosal epithelium of the pharynx.

Result Analysis
Print
Save
E-mail