1.Moxibustion at different temperatures for cognitive impairment in type 2 diabetes mellitus: a randomized controlled trial.
Yan WEI ; Yuhao QU ; Aihong YUAN ; Lele ZHANG ; Min YE ; Qunwei LI ; Hongyu XIE
Chinese Acupuncture & Moxibustion 2025;45(9):1233-1240
OBJECTIVE:
To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM).
METHODS:
A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment.
RESULTS:
After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05).
CONCLUSION
Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans
;
Diabetes Mellitus, Type 2/therapy*
;
Male
;
Female
;
Moxibustion
;
Middle Aged
;
Aged
;
Cognitive Dysfunction/psychology*
;
Cognition
;
Temperature
;
Blood Glucose/metabolism*
;
Adult
;
Acupuncture Points
2.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
;
Humans
;
Consensus
;
Drugs, Chinese Herbal/therapeutic use*
;
Surveys and Questionnaires
3.Differential expressions of exosomal miRNAs in patients with chronic heart failure and hyperuricemia: diagnostic values of miR-27a-5p and miR-139-3p.
Zhiliang CHEN ; Yonggang YANG ; Xia HUANG ; Yan CHENG ; Yuan QU ; Qiqi HENG ; Yujia FU ; Kewei LI ; Ning GU
Journal of Southern Medical University 2025;45(1):43-51
OBJECTIVES:
To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes.
METHODS:
This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment.
RESULTS:
A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment.
CONCLUSIONS
Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans
;
Hyperuricemia/diagnosis*
;
Heart Failure/genetics*
;
MicroRNAs/metabolism*
;
Exosomes/metabolism*
;
Chronic Disease
;
Male
;
Female
;
Middle Aged
;
Animals
4.Deep learning radiomics nomogram based on intra- and peri-tumoral MRI for differentiating IgG4-related ophthalmic disease from orbital MALT Lymphoma
Chenran ZHOU ; Xinyan2 WANG ; Xiaozheng DU ; Jie LI ; Qinghai YUAN ; Xiaoxia QU ; Qinghe HAN
Chinese Journal of Radiology 2025;59(10):1126-1132
Objective:To investigate the value of a deep learning radiomics (DLR) nomogram model based on intra-tumoral and peri-tumoral MRI features for differentiating IgG4-related ophthalmic disease (IgG4-ROD) from orbital mucosa-associated lymphoid tissue (MALT) lymphoma.Methods:This was a case-control study. The clinical and imaging data of 233 patients pathologically confirmed with either IgG4-ROD or orbital MALT lymphoma were retrospective collected between January 2020 and December 2024 from the Second Hospital of Jilin University (Center 1) and Beijing Tongren Hospital, Capital Medical University (Center 2). Patients from Center 1 ( n=158) were used as the training cohort, while those from Center 2 ( n=75) served as the validation cohort. Among the cases, 102 were IgG4-ROD (70 in training, 32 in validation) and 131 were orbital MALT lymphoma (88 in training, 43 in validation). Univariate and multivariate logistic regression analyses were used to identify independent clinical imaging predictors and build a clinical imaging model. Based on T 1WI, T 2WI, and diffusion weighted images, intra-tumoral regions were manually delineated, a 2 mm peri-tumoral margin was automatically generated, and both regions were combined as a single region of interest for radiomics feature extraction. Deep learning features were extracted using a ResNet-50 backbone, and after feature selection and dimensionality reduction, a DLR model was constructed. The clinical imaging features and DLR features were integrated to build a combined nomogram model. Model performance in differentiating IgG4-ROD from orbital MALT lymphoma was assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis. The area under the curve (AUC) were compared using the DeLong test. Results:Bilateral orbital involvement ( OR=1.983, 95% CI 1.166-2.843, P=0.046) and extraocular muscle involvement ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as independent predictors for distinguishing IgG4-ROD from orbital MALT lymphoma and were used to construct the clinical model. Fourteen features (9 radiomics and 5 deep learning features) were selected for the DLR model, and a nomogram was developed. In the training set, the AUCs for the clinical model, DLR model, and nomogram were 0.762 (95% CI 0.712-0.812), 0.865 (95% CI 0.822-0.908), and 0.943 (95% CI 0.909-0.953), respectively. In the validation set, the AUCs were 0.733 (95% CI 0.675-0.791), 0.823 (95% CI 0.762-0.884), and 0.924 (95% CI 0.902-0.958), respectively. The nomogram showed significantly higher AUCs than those of the clinical and DLR models alone (training set: Z=3.92, 2.87, P0.001, P=0.004; validation set: Z=3.25, 2.46, P=0.001, 0.014). Calibration curves indicated good agreement between predicted and actual IgG4-ROD incidence, and decision curve analysis demonstrated the highest net benefit for the nomogram. Conclusion:A nomogram that incorporates both intra-tumoral and peri-tumoral DLR features and clinical imaging characteristics demonstrates excellent performance in distinguishing IgG4-ROD from orbital MALT lymphoma.
5.Central nervous system infection:Expert consensus on imaging examination standards(2024 edition)
Chen QIAO ; Ting LIU ; Jianming CAI ; Qing LU ; Weijun SITU ; Meng ZHENG ; Zhenying XIA ; Yuan QU ; Ting LIANG ; Guangping ZHENG ; Hongkai ZHANG ; Shengyuan LAI ; Hongjun LI
Chinese Journal of Medical Imaging Technology 2025;41(6):857-860
Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.
6.Study on the medication rules of traditional Chinese medicine in treating breast cancer based on data mining
Yuan LI ; Lin QIAN ; Chao TIAN ; Tao WU ; Lyuhui HU ; Bingmei ZHU ; Zhihua YE ; Zhizhen TAO ; Min YANG ; Qinxi LIU ; Bihui YANG ; Hang LUO ; Fan QU ; Yi YANG
China Modern Doctor 2025;63(24):68-72,129
Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94%of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55%),warm-natured(30.05%),and neutral-natured(23.34%)drugs were predominant;In terms of five flavors,sweet(46.12%),bitter(30.91%),and pungent(20.02%)were the main ones.The most frequently used drugs were tonifying herbs(32.77%),followed by heat-clearing herbs(15.96%)and phlegm-resolving herbs(14.71%).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.
7.Association of urine cadmium levels with thyroid hormone levels among middle-aged and older adults aged 40-89 years in selected areas of China
Changzi WU ; Xiaochen WANG ; Yue CHEN ; Zheng LI ; Yi ZHANG ; Yuan WEI ; Bing WU ; Wenli ZHANG ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Xiu YE ; Luxi WEI ; Yingli QU ; Haiyan CHU ; Yuebin LYU ; Ying ZHU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(2):209-215
Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.
8.Role of hippocampal activating transcription factor 5 in cognitive impairment induced by neuropathic pain in mice: relationship with mitochondrial unfolded protein response
Fei XING ; Xiaoshan SHI ; Yaowei XU ; Xin WEI ; Mingcui QU ; Dan CHENG ; Jingjing YUAN ; Zhongyu WANG ; Na XING ; Yanna LI
Chinese Journal of Anesthesiology 2025;45(3):329-334
Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.
9.Clinical pathway for integrated traditional Chinese and Western medicine in the diagnosis and treatment of acute pancreatitis
Yuan ZHANG ; Hao WANG ; Haiyan YIN ; Shengwei JIN ; Bangjiang FANG ; Guiwei LI ; Xijing ZHANG ; Hongmei GAO ; Donghao WANG ; Changsong WANG ; Keliang XIE ; Lai JIANG ; Yan QU ; Zhaocai ZHANG ; Jianying KAN ; Daihua YU ; Junling LIU ; Jun LI ; Weiwei AN ; Yong CHEN ; Jianbo YU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(3):257-261
Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.
10.Heterologous Expression,Purification and Enzymatic Characterization of Xylitol Dehydrogenase from the Thermophilic Fungus Talaromyces emersonii
Er MENG ; Cong QU ; Ke YI ; Hui-Min LI ; Xin-Yi DUAN ; Zhe-Yuan ZHANG ; Shao-Long HE ; Yu-Tao LUO ; Lei WU ; Dong-Yi ZHANG ; Chang-Jun LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):1007-1018
The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Result Analysis
Print
Save
E-mail