1.Material Basis of Anti-Inflammatory Efficacy and Mechanism of Action of Bushen Tongdu Prescription Based on UPLC-LTQ-Orbitrap-MS and Network Pharmacology
Yan RONG ; Lulu JING ; Hongping HOU ; Huijun WANG ; Lihua CHEN ; Yunxin CHEN ; Liang LI ; Li LIN ; Xiaoqin LUO ; Haiyu ZHAO ; Xiaolu WEI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):152-161
ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription (BSTDP). MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-LIT-Orbitrap-MS). Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction (PPI) network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg (mpx: GFP). At three days post-fertilization (3 dpf), larvae of zebrafish were randomly assigned to blank group, model group, positive drug dexamethasone acetate group (75 μmol·L-1), and BSTDP groups with low, medium, and high doses (500, 1 000, and 2 000 mg·L-1). The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway and inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). ResultsA total of 120 chemical components were identified in BSTDP, among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis (RA) and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine, vomicine, sinapine, rehmannioside, cinnamyl alcohol glycoside, and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 (Akt1), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), TLR4, mitogen-activated protein kinase 14 (MAPK14), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L-1. Compared to those in the blank group, zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region (P<0.01) and rising mRNA levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β (P<0.01). Compared to that in the model group, the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses, as well as the dexamethasone acetate group (P<0.05, P<0.01). There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β were significantly down-regulated (P<0.05, P<0.01). ConclusionThis paper identifies the material basis of the efficacy of BSTDP, demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.
2.Material Basis of Anti-Inflammatory Efficacy and Mechanism of Action of Bushen Tongdu Prescription Based on UPLC-LTQ-Orbitrap-MS and Network Pharmacology
Yan RONG ; Lulu JING ; Hongping HOU ; Huijun WANG ; Lihua CHEN ; Yunxin CHEN ; Liang LI ; Li LIN ; Xiaoqin LUO ; Haiyu ZHAO ; Xiaolu WEI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):152-161
ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription (BSTDP). MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-LIT-Orbitrap-MS). Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction (PPI) network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg (mpx: GFP). At three days post-fertilization (3 dpf), larvae of zebrafish were randomly assigned to blank group, model group, positive drug dexamethasone acetate group (75 μmol·L-1), and BSTDP groups with low, medium, and high doses (500, 1 000, and 2 000 mg·L-1). The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway and inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). ResultsA total of 120 chemical components were identified in BSTDP, among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis (RA) and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine, vomicine, sinapine, rehmannioside, cinnamyl alcohol glycoside, and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 (Akt1), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), TLR4, mitogen-activated protein kinase 14 (MAPK14), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L-1. Compared to those in the blank group, zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region (P<0.01) and rising mRNA levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β (P<0.01). Compared to that in the model group, the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses, as well as the dexamethasone acetate group (P<0.05, P<0.01). There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β were significantly down-regulated (P<0.05, P<0.01). ConclusionThis paper identifies the material basis of the efficacy of BSTDP, demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.
3.The effect of ankle pump exercise with colorful ring counting command on the blood hypercoagulable state in patients after hepatic arterial infusion chemotherapy
Feng JIANG ; Xiaoqin LIANG ; Tingting LIN ; Shuang JIN ; Haijun TANG
Journal of Interventional Radiology 2025;34(11):1259-1264
Objective To discuss the application of ankle pump exercise with colorful ring counting command in improving the blood hypercoagulable state in patients after hepatic arterial infusion chemotherapy(HAIC).Methods A total of 105 patients,who received HAIC at the Interventional Department of a certain Grade A general hospital in Fujian Province of China from January to December of 2023,were collected.The 53 patients who received treatment from January to June of 2023 were used as the control group,and the other 52 patients who received treatment from July to December of 2023 were used as the study group.The postoperative routine nursing and ankle pump exercise was employed for the patients of the control group,while ankle pump exercise with colorful ring counting command on the basis of postoperative routine nursing was carried out for the patients of the study group.The resting status of popliteal vein,the maximum and average systolic blood flow velocity at the end of exercise,the changes in coagulation index,the incidence of deep vein thrombosis,and the compliance of ankle pump were compared between the two groups.Results There were no statistically significant differences in the resting popliteal vein blood flow velocity and incidence of deep vein thrombosis between the two groups(P>0.05).The maximum and average popliteal vein blood flow velocity at the end of exercise in the study group were higher than those in the control group.The levels of PT,APTT,FBG,TT and D-dimer(D-D)at 72 hours after HAIC were lower than those in the control group(all P<0.05),and the compliance of ankle pump exercise in the study group was better than that in the control group(P<0.05).Conclusion Ankle pump exercise with colorful ring counting command can accelerate lower limb blood flow velocity,improve the blood hypercoagulable state,and improve compliance with ankle pump exercise in patients after receiving HAIC.
4.Evaluation of the outcomes of cochlear implant in children with auditory neuropathy
Cuncun REN ; Ying LIN ; Xiaoqin FAN ; Pengfei LIANG ; Xinyu ZHANG ; Zejun GAO ; Dingjun ZHA
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(5):432-438
Objective:To investigate the auditory and speech abilities of children with congenital auditory neuropathy (AN) after cochlear implant (CI), and to analyze the role of genetic testing in predicting the postoperative outcomes of CI in AN patients.Methods:Fourteen children diagnosed with AN by audiological battery test and underwent CI surgery in Xijing Hospital of the Air Force Medical University from 2002 to 2021 were included in this study (9 males and 5 females), with an implantation age of (3.1±1.7) years (mean±standard deviation, the same as follows). The preoperative audiological results and deafness gene results were analyzed. Another 52 children with ordinary sensorineural hearing loss (SNHL) were selected as the control group (30 males and 22 females), with an implantation age of (2.2±0.9) years. The demographic factors such as age and gender were matched with those of the AN group. The modified Category Auditory Performance (CAP-Ⅱ) and Speech Intelligence Rate (SIR) were used to evaluate the development of postoperative auditory and speech abilities in two groups. The Mandarin Speech Test System was used to test the speech recognition rate of monosyllabic and disyllabic words and sentences. Matlab 2022 software was used to analyze the data.Results:The results of gene in 14 children with AN showed that 6 cases had OTOF gene mutations, 2 cases (siblings) were confirmed to have TNN gene mutations through whole exome sequencing, and the remaining 6 cases were not find any clear pathogenic gene mutations. All subjects underwent CI surgery with electrodes implanted into the cochlea smoothly, and there were no postoperative complications. After surgery, all AN children had improved auditory and speech abilities, but only 64% (9/14) of AN children with CI had auditory ability scores comparable to the control group of SNHL children (including 2 children with TNN gene mutations), and 36% (5/14) of AN children had lower scores than the control group of SNHL children.The average speech recognition rate of two children with TNN gene mutations was 86.5%, and of two children with OTOF gene mutations was 83.2%. Conclusions:AN children achieved varying degrees of auditory and speech abilities after CI, but the postoperative effects varied greatly. Some children achieved similar results as ordinary SNHL children, but there were still some children whose effects were worse than those of ordinary SNHL children. The postoperative efficacy of CI in two children with AN caused by TNN pathogenic genes were comparable to that of ordinary SNHL in children. Genetic testing had certain reference value for predicting the postoperative effect of CI in AN children.
5.Clinical value of abdominal adipose volume in predicting early tumor recurrence after resec-tion of hepatocellular carcinoma
Guojiao ZUO ; Mi PEI ; Zongqian WU ; Fengxi CHEN ; Jie CHENG ; Yiman LI ; Chen LIU ; Xingtian WANG ; Xuejuan KONG ; Lin CHEN ; Xiaoqin YIN ; Hongyun RAO ; Wei CHEN ; Ping CAI ; Xiaoming LI
Chinese Journal of Digestive Surgery 2024;23(1):140-146
Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.
6.Current status of post competency evaluation index system for general practitioners in China: a systematic review
Ting LI ; Yuan LIN ; Xiaoqin LU ; Guanghui JIN
Chinese Journal of General Practitioners 2024;23(4):345-353
Objective:To explore the current status of the post competency evaluation index systems of Chinese general practitioners (GPs), and to summarize the post competency evaluation index systems of GPs in China.Methods:This study was a systematic review. We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database (CQVIP), SinoMed, PubMed and other databases using "general practitioner" or "family doctor" or "standardized training for residents" or "post competency" or "evaluation system" or "core capability" or "assessment" or "evaluation" etc. as search terms and adding free words. The search was conducted from data establishment to October 2022. Literature screening and data extraction were carried out independently by 2 researchers using strict inclusion and exclusion criteria. The Ekman quality evaluation tool was used to evaluate the quality of the included literature. Excel was used to extract data information, including basic information of literatures, basic information of index systems and index content.Results:A total of 1 284 literatures were retrieved and 33 studies were included. A total of 15 research methods were used, and 28 (84.8%) applied 3 or more methods. There were 14 studies (42.4%) with good reliability and validity, and 17 studies (51.5%) with index weights. There were 12 applied theoretical bases, of which 20 studies (60.6%) used mature foreign competency models as a reference, 14 studies (42.4%) combined the job analysis and position requirements of GPs, and 11 studies (33.3%) interpreted policy documents. The content analysis method yielded 1 537 initial indicators, 1 268 indicators after eliminating repeated indicators, and 6 first-level indicators and 31 second-level indicators after combining and summarizing. Among the first-level indexes, "patient care" appeared most frequently (36.4% (462/1 268)); the secondary index with the highest frequency in this dimension was "master medical theoretical knowledge" followed by "community-oriented care ability" and "treatment and follow-up of common and frequently-occurring diseases"; the indicators "family-based care ability" and "human-centered care concept" reflected the characteristics of general medical practice. The frequency of "professional spirit and moral quality" (16.3%(207/1 268)), "clinical teaching and learning ability" (14.3%(181/1 268)) and "system-based practical ability"(11.1%(141/1 268)) ranked second, third and fourth among the first-level indicators respectively. The frequency of "basic public health service ability" (11.0%(139/1 268)) ranked the fifth, and the secondary indicator "health management of key community groups" reflected the concept of the whole life cycle of residents and the basic principle of continuity of care in general medicine. The frequency of "interpersonal and communication skills"(10.9%(138/1 268)) ranked sixth.Conclusions:There have been numerous researches on the post competency index evaluation system of GPs in China, but more research is still needed. There are many research methods with rich theoretical basis and Chinese characteristics. This study summarized the post competency evaluation index systems of GPs in China, generalized 6 first-level indicators and 31 second-level indicators that reflect the basic principles and characteristics of general medicine.
7.A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2.
Zijing JIA ; Kang WANG ; Minxiang XIE ; Jiajing WU ; Yaling HU ; Yunjiao ZHOU ; Ayijiang YISIMAYI ; Wangjun FU ; Lei WANG ; Pan LIU ; Kaiyue FAN ; Ruihong CHEN ; Lin WANG ; Jing LI ; Yao WANG ; Xiaoqin GE ; Qianqian ZHANG ; Jianbo WU ; Nan WANG ; Wei WU ; Yidan GAO ; Jingyun MIAO ; Yinan JIANG ; Lili QIN ; Ling ZHU ; Weijin HUANG ; Yanjun ZHANG ; Huan ZHANG ; Baisheng LI ; Qiang GAO ; Xiaoliang Sunney XIE ; Youchun WANG ; Yunlong CAO ; Qiao WANG ; Xiangxi WANG
Protein & Cell 2024;15(12):930-937
8.Correlation between uterine incisional hematoma following cesarean section and scar diverticulum
Huibin XIAO ; Xiaoyan LIN ; Wenyue LU ; Xiaoqin LIANG ; Min ZHONG
Chinese Journal of Perinatal Medicine 2023;26(12):1029-1032
Objective:To investigate the correlation between the uterine incisional hematoma following cesarean section and scar diverticulum.Methods:This is a retrospective study involving 1 939 women who underwent cesarean section for the first time at the People's Hospital of Longhua Shenzhen from January 2020 to December 2021. Women with uterine incisional hematoma were selected as the hematoma group ( n=149) and were further divided into the dehiscence group, including patients with uterine incisional dehiscence caused by hematoma, and non-dehiscence group, including those without uterine incisional dehiscence. The patients without uterine incisional hematoma during the same period were selected as the control group ( n=110). The incidence of scar diverticulum after uterine incision healing and the long-term outcomes in the two groups were compared. Statistical analysis was performed using a t-test or Chi-square test. Results:(1) The incidence of uterine incisional hematoma was 7.7% (149/1 939). In the 149 cases with uterine incisional hematoma detected by postoperative ultrasonography, 74 were in the dehiscence group and 75 in the non-dehiscence group. (2) The number of women developing cesarean section scar diverticulum was 41, with an incidence of 2.1% (41/1 939), and all of them were in the hematoma group, accounting for 27.5% (41/149). The proportion of women who developed scar diverticulum in the dehiscence group was higher than that of the non-dehiscence group [52.7% (39/74) vs. 2.7% (2/75), χ2=35.96, P<0.001]. (3) The incidence of scar diverticulum in patients with uterine incisional dehiscence caused by intra-incision hematoma, intra- and posterior incision hematoma, as well as a combination of intra-, anterior, and posterior incision hematoma were 10/18, 55.1% (27/49), and 2/2, respectively. None of the five patients with uterine scar diverticulum were caused by anterior incision hematoma plus partial intra-incision hematoma. The incidence of scar diverticulum was 2.7% (2/75) in the non-dehiscence group. (4) Among the 41 cases with scar diverticulum, ultrasound re-examination by postpartum 6-24 months found that the results of 40 (97.6%) cases were consistent with the last ultrasound findings. A small "v"-shaped scar diverticulum was observed in another patient by ultrasound 42 d after delivery, which disappeared in a re-examination 13 months after surgery. Conclusions:Uterine incisional hematoma is associated with scar diverticulum following cesarean section. Uterine incisional dehiscence due to hematoma may be an influencing factor for diverticulum formation.
9.Identification of Components and Metabolites of Leaves of Cyclocarya Paliurus in Rats Plasma by UHPLC-Q/TOF-MS
ZHANG Xiaoqin ; LIN Bingfeng ; LIU Shuang ; LEI Houxing ; CHEN Liping ; WANG Nani
Chinese Journal of Modern Applied Pharmacy 2023;40(17):2435-2445
OBJECTIVE To investigate the components and metabolites of leaves of Cyclocarya paliurus in rats plasma. METHODS UHPLC-Q/TOF-MS method was applied to identify the components and metabolites of rat plasma. The prototype components and metabolites were analyzed in rats plasma of leaves of Cyclocarya paliurus water extract after intragastric administration by comparing the chromatograms of Cyclocarya paliurus, blank serum and drug-containing serum. RESULTS A total of 15 compounds including 6 prototype components and 9 metabolites were identified. The main prototype components in blood were caffeylquinic acid, flavonoids and saponins, and the metabolic pathways were methylation and hydroxylation. CONCLUSION This experiment showes that the prototype components absorbed into blood may be the potential bioactive components in leaves of Cyclocarya paliurus, providing a scientific basis for clarifying its material basis in pharmacodynamics.
10.Characteristics of whole blood donors from 26 blood stations before and after the outbreak of COVID-19:a multicenter study
Peng LI ; Youhua SHEN ; Wei GAO ; Wei ZHANG ; Jianling ZHONG ; Hao LI ; Lin BAO ; Ying WANG ; Xuefang FENG ; Tao SUN ; Xiaoqin CHEN ; Li LI ; Hongzhi JIA ; Shouguang XU ; Xiaobo CAI ; Wen ZHANG ; Qunying LAI ; Zhiqiang YU ; Zhenxing WANG ; Yanjun ZHOU ; Peng WANG ; Yanhua ZHANG ; Guoqiang ZHANG ; Haiying NIU ; Hongli JING
Chinese Journal of Blood Transfusion 2023;36(10):907-912
【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.


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