1.Network toxicology and its application in studying exogenous chemical toxicity
Yanli LIN ; Zehua TAO ; Zhao XIAO ; Chenxu HU ; Bobo YANG ; Ya WANG ; Rongzhu LU
Journal of Environmental and Occupational Medicine 2025;42(2):238-244
With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.
2.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
3.Expert consensus on the application of nasal cavity filling substances in nasal surgery patients(2025, Shanghai).
Keqing ZHAO ; Shaoqing YU ; Hongquan WEI ; Chenjie YU ; Guangke WANG ; Shijie QIU ; Yanjun WANG ; Hongtao ZHEN ; Yucheng YANG ; Yurong GU ; Tao GUO ; Feng LIU ; Meiping LU ; Bin SUN ; Yanli YANG ; Yuzhu WAN ; Cuida MENG ; Yanan SUN ; Yi ZHAO ; Qun LI ; An LI ; Luo BA ; Linli TIAN ; Guodong YU ; Xin FENG ; Wen LIU ; Yongtuan LI ; Jian WU ; De HUAI ; Dongsheng GU ; Hanqiang LU ; Xinyi SHI ; Huiping YE ; Yan JIANG ; Weitian ZHANG ; Yu XU ; Zhenxiao HUANG ; Huabin LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(4):285-291
This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans
;
Nasal Cavity/surgery*
;
Nasal Surgical Procedures
;
China
;
Consensus
;
Sinusitis/surgery*
;
Dermal Fillers
4.Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.
Yufei HUI ; Xue JIAO ; Li YANG ; Dejin LU ; Yanbo HAN ; Wen YANG ; Yanli CAO ; Yuxi MIAO ; Shiqiang GONG ; Minjie WEI
Acta Pharmaceutica Sinica B 2025;15(7):3404-3418
Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.
5.Efficacy,safety and cost-effectiveness evaluation of voriconazole original and generic drugs
Ganling TANG ; Xiangwei XIE ; Xiandan LUO ; Yanli LU ; Huixian JIANG ; Jingyi LI ; Xiaoman HUANG ; Hongliang ZHANG
China Pharmacy 2024;35(7):831-836
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of generic drugs and original drugs of voriconazole. METHODS The information of patients who used voriconazole generic drugs selected in National Centralized Drug Procurement (generic drug group) or non-selected original drugs (original drug group) in the treatment of fungal infection was collected from the our hospital. The propensity score matching was carried out to eliminate bias. The comprehensive efficacy was evaluated according to clinical efficacy, image findings and microbiological test, and stratified analysis of different populations was conducted based on fungal species, underlying diseases, etc., the efficacy of different stratifications was evaluated. Evaluation of safety was performed by using the incidence of adverse reactions. The total cost, defined daily doses (DDDs) and defined daily dose cost (DDDc) were used to evaluate the cost-effectiveness. RESULTS A total of 436 patients were included, and there were 190 patients in each group after matching. In terms of efficacy, the effective rates of voriconazole generic drugs and original drugs were 62.63% and 59.47% (P=0.528); in terms of safety, the incidence of adverse reactions caused by generic drugs and original drugs of voriconazole was 13.68% and 7.89%, respectively(P=0.069). In terms of cost-effectiveness, the average total cost of generic drugs was 4 636.26 yuan, and that of original drugs was 8 613.20 yuan (P<0.001). After the implementation of National Centralized Drug Procurement, replacement rate of generic drugs increased to 87.30%, and DDDc decreased by 59.08%. CONCLUSIONS The efficacy and safety of voriconazole generic drugs are similar to those of original drugs in the treatment of fungal infection, and it is more cost-effective in terms of treatment cost.
6.Study on metabolites derived from Zhideke granules in rats in vivo
Jie LIANG ; Piaoxue ZHENG ; Huihua CHEN ; Chunyan HUANG ; Yanli LIANG ; Chunlian LU ; Jingjing XIE ; Yuming MA ; Jiawen PENG ; Lichun ZHAO ; Rilan CHEN
China Pharmacy 2024;35(2):172-178
OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group (Zhideke granules, 9.45 g/kg); they were given ultrapure water or relevant medicine, twice a day, every 6-8 h, for 3 consecutive days. Serum, urine and feces samples of rats were collected, and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules; their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules, 16 prototype components (i.g. irisflorentin, baicalin, chlorogenic acid) and 11 metabolites (i.g. hydration products of kaempferol or luteolin, methylation products of chlorogenic acid, and hydroxylation products of baicalin) were identified in serum, urine and feces of rats. Among them, 8 prototype components and 4 metabolites were identified in serum samples; 10 prototype components and 7 metabolites were identified in urine samples; 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin, irisflorentin,chlorogenic acid, and the main metabolic pathways included methylation, hydroxylation, glucuronidation.
7.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
8.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
9.Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease
Yuan TANG ; Yanping SHI ; Lu CHEN ; Yifang SUO ; Shengen LIAO ; Cheang LOKFAI ; Yanli ZHOU ; Rongrong GAO ; Jing SHI ; Wei SUN ; Hao ZHANG ; Yanhui SHENG ; Rong YANG ; Xiangqing KONG ; Xinli LI ; Haifeng ZHANG
Chinese Journal of Cardiology 2024;52(10):1177-1185
Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.
10.Clinical evaluation for rapid detection of carbapenemase produced by Klebsiella pneumoniae and Pseudomonas aeruginosa u-sing Autof MS 1000 mass spectrometry identification system
Dan LU ; Yanli SHEN ; Wang WEI ; Xueting ZHOU ; Yujie CAO ; Qian PAN ; Kui XUE
Chinese Journal of Clinical Laboratory Science 2024;42(10):744-747
Objective To investigate the clinical value of matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS)in rapid detection of carbapenemase produced by Klebsiella pneumoniae and Pseudomonas aeruginosa.Methods A total of 60 strains of Klebsiella pneumoniae and 80 strains of Pseudomonas aeruginosa isolated from Pizhou People's Hospital affiliated to Xuzhou Medical University from January 2022 to October 2023 were collected,including 30 strains of carbapenem-resistant Klebsiella pneumoniae(CRKP),30 strains of carbapenem-sensitive Klebsiella pneumoniae(CSKP),50 strains of carbapenem-resistant Pseudo-monas aeruginosa(CRPA)and 30 strains of carbapenem-sensitive Pseudomonas aeruginosa(CSPA).Three detection methods were applied,i.e.,modified carbapenem inactivation method(mCIM),colloidal gold immunochromatography and Autof MS 1000 mass spectrometry identification system to evaluate the ability of Autof MS 1000 mass spectrometry identification system in detecting carbape-nase production of Klebsiella pneumoniae and Pseudomonas aeruginosa.Results The results of Autof MS 1000 mass spectrometry iden-tification system were consistent with those of both mCIM and colloidal gold immunochromatography.Carbapenemase was detected in 28 of the 30 CRKP strains,and it was negative in 2 CRKP strains.Carbapenamase was detected in 15 of the 50 CRPA strains and it was negative in 35 CRPA strains.Thirty strains of CSKP and 30 strains of CSPA were all Carbapenemase negative.The coincidence rate of the results of the three methods in the detection for carbapenase was 100%.Conclusion The result of Autof MS 1000 mass spectrome-try identification system has been consistent with those of mCIM and colloidal gold immunochromatography.It not only has the charac-teristics of cost-saving compare with of mCIM method,but also hold the advantages of fast speed and high accuracy of colloidal gold im-munochromatography method.Thus,Autof MS 1000 system can be used for the rapid identification of carbapenemase produced by Kleb-siella pneumoniae and Pseudomonas aeruginosa.

Result Analysis
Print
Save
E-mail