1.The relationship between fat attenuation index of pericoronary adipose tissue and coro-nary slow flow
Aixia LIANG ; Jingwu WANG ; Min XU ; Qian WANG ; Kelu SUN
Chinese Journal of Arteriosclerosis 2025;33(10):864-869
Aim To investigate the relationship between fat attenuation index(FAI)of pericoronary adipose tis-sue and coronary slow flow(CSF).Methods The clinical data of 135 hospitalized patients who underwent coronary angiography(CAG)due to chest tightness,chest pain and other similar symptoms from November 2023 to July 2024 were retrospectively collected.According to the blood flow grading criteria,the patients were divided into CSF group(n=61)and normal blood flow group(n=74).The basic information of the patients,the laboratory test results on the day of ad-mission and the data of coronary CT angiography(CCTA)were also collected.Multivariate Logistic regression was used to analyze the risk factors for CSF.The receiver operating characteristic(ROC)curve was used to evaluate the efficacy of FAI in predicting CSF.Results The white blood cell count(WBC),fasting blood glucose(FBG),high-sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6)and right coronary artery(RCA)FAI in the CSF group were 1.23,1.10,1.33 1.53 and 1.13 times that of those in the normal blood flow group,respectively(P<0.05).The left ventricu-lar ejection fraction(LVEF)in the CSF group was 94.78%of the normal blood flow group(P<0.05).Multivariate Lo-gistic regression analysis showed that elevated WBC(OR=1.891),elevated FBG(OR=1.774),decreased LVEF(OR=0.094),elevated hs-CRP increased(OR=1.124),increased RCA-FAI(OR=1.077)were independent risk factors for CSF(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of RCA-FAI in predic-ting CSF was 0.715(95%CI:0.627~0.802),the optimal cut-off value was-81.5 HU,the sensitivity was 0.803,and the specificity was 0.581.Conclusion Elevated WBC,elevated FBG,decreased LVEF,increased hs-CRP,and in-creased RCA-FAI are risk factors for CSF.Among them,RCA-FAI has a good efficacy in predicting the occurrence of CSF,which can be used to identify high-risk CSF patients as early as possible and reduce the incidence of CSF.
2.Effect of wogonin on nerve injury in rats with diabetic cerebral infarction
Huanhuan WANG ; Panpan LIANG ; Jinshui YANG ; Shuxian JIA ; Jiajia ZHAO ; Yuanyuan CHEN ; Qian XUE ; Aixia SONG
Chinese Journal of Tissue Engineering Research 2025;29(11):2327-2333
BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.
3.The relationship between fat attenuation index of pericoronary adipose tissue and coro-nary slow flow
Aixia LIANG ; Jingwu WANG ; Min XU ; Qian WANG ; Kelu SUN
Chinese Journal of Arteriosclerosis 2025;33(10):864-869
Aim To investigate the relationship between fat attenuation index(FAI)of pericoronary adipose tis-sue and coronary slow flow(CSF).Methods The clinical data of 135 hospitalized patients who underwent coronary angiography(CAG)due to chest tightness,chest pain and other similar symptoms from November 2023 to July 2024 were retrospectively collected.According to the blood flow grading criteria,the patients were divided into CSF group(n=61)and normal blood flow group(n=74).The basic information of the patients,the laboratory test results on the day of ad-mission and the data of coronary CT angiography(CCTA)were also collected.Multivariate Logistic regression was used to analyze the risk factors for CSF.The receiver operating characteristic(ROC)curve was used to evaluate the efficacy of FAI in predicting CSF.Results The white blood cell count(WBC),fasting blood glucose(FBG),high-sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6)and right coronary artery(RCA)FAI in the CSF group were 1.23,1.10,1.33 1.53 and 1.13 times that of those in the normal blood flow group,respectively(P<0.05).The left ventricu-lar ejection fraction(LVEF)in the CSF group was 94.78%of the normal blood flow group(P<0.05).Multivariate Lo-gistic regression analysis showed that elevated WBC(OR=1.891),elevated FBG(OR=1.774),decreased LVEF(OR=0.094),elevated hs-CRP increased(OR=1.124),increased RCA-FAI(OR=1.077)were independent risk factors for CSF(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of RCA-FAI in predic-ting CSF was 0.715(95%CI:0.627~0.802),the optimal cut-off value was-81.5 HU,the sensitivity was 0.803,and the specificity was 0.581.Conclusion Elevated WBC,elevated FBG,decreased LVEF,increased hs-CRP,and in-creased RCA-FAI are risk factors for CSF.Among them,RCA-FAI has a good efficacy in predicting the occurrence of CSF,which can be used to identify high-risk CSF patients as early as possible and reduce the incidence of CSF.
4.Spatiotemporal distribution characteristics of syphilis in Gansu province in 2005 - 2021
Li LI ; Aixia TU ; Qijun LIANG ; Jianjun YANG ; Xiaoqiang YANG ; Huihui YANG
Journal of Public Health and Preventive Medicine 2024;35(4):53-57
Objective To analyze the spatiotemporal distribution characteristics of the syphilis epidemic in Gansu Province from 2005 to 2021, and to provide a reference for the prevention and control of the syphilis epidemic in Gansu Province. Methods ArcGIS 10.7 was used to map the annual incidence of syphilis in Gansu Province from 2005 to 2021, spatial autocorrelation analysis and local autocorrelation analysis were performed, and SaTScan 10.0.2 software was used for spatiotemporal scanning analysis. Results The global autocorrelation results showed that the annual incidence of syphilis in 2005-2021 was >0, Z>1.96, and the P< 0.0001, showing a spatial clustering distribution, and the local autocorrelation results showed that there was one spatially similar high-high aggregation area and two spatially similar low-low aggregation areas in Gansu Province, and the hot spot analysis showed that there were 9 negative hotspot areas and 2 positive hotspot areas in the syphilis epidemic in Gansu Province. Spatiotemporal scanning analysis detected two high concentration areas, mainly concentrated in Gannan Tibetan Autonomous Prefecture. Conclusion Syphilis in Gansu Province has regional differences in space, and high-high accumulation areas in Gannan Tibetan Autonomous Prefecture persist, and targeted prevention and control strategies should be specified according to temporal and spatial characteristics.
5.Evaluation value of serum soluble programmed cell death protein 1, soluble B7 homolog 5 molecules combined with trefoil factor 2 on disease severity and death risk in patients with acute pancreatitis
Renjuan XING ; Pengcheng YIN ; Huanhuan LIANG ; Aixia TIAN
Chinese Journal of Postgraduates of Medicine 2023;46(5):422-428
Objective:To investigate the value of serum soluble programmed cell death protein 1 (sPD-1), soluble B7 homolog 5 (sB7-H5) and trefoil factor 2 (TFF2) in evaluating the severity of disease and the risk of death in patients with acute pancreatitis (AP).Methods:A prospective research method was adopted. Three hundred and twenty-eight patients with AP (AP group) from February 2020 to February 2021 in Xiangyang Central Hospital were selected, including 124 patients with mild AP (MAP), 106 patients with moderately severe AP (MSAP) and 98 patients with severe AP (SAP). The serum levels of sPD-1, sB7-H5 and TFF2 were measured by enzyme-linked immunosorbent assay and compared with 60 healthy people (healthy control group). The patients with AP were followed up for 90 d, 284 patients survived and 44 died. The amylase, C-reactive protein (CRP), procalcitonin (PCT), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), modified CT severity index (MCTSI), sPD-1, sB7-H5 and TFF2 were compared between the two groups. Pearson method was used for correlation analysis. Multivariate Logistic regression was used to analyze the independent risk factors of death in patients with AP. The efficacy of sPD-1, sB7-H5 and TFF2 in predicting the death in patients with AP was evaluated using the receiver operating characteristics (ROC) curve.Results:The sPD-1, sB7-H5 and TFF2 in AP group were significantly higher than those in healthy control group: (177.99 ± 17.81) ng/L vs. (50.20 ± 10.81) ng/L, (2.69 ± 0.72) μg/L vs. (1.40 ± 0.35) μg/L and (569.97 ± 38.91) μg/L vs. (94.59 ± 11.98) μg/L, and there were statistical differences ( P<0.01). The amylase, sPD-1, sB7-H5 and TFF2 in patients with MSAP and SAP were significantly higher than those in patients with MAP: (639.36 ± 91.67) and (835.24 ± 109.30) U/L vs. (575.24 ± 89.78) U/L, (180.13 ± 20.61) and (221.17 ± 15.70) ng/L vs. (142.03 ± 16.76) ng/L, (2.85 ± 0.74) and (3.34 ± 0.82) μg/L vs. (2.05 ± 0.52) μg/L, (539.66 ± 36.58) and (763.55 ± 40.08) μg/L vs. (442.90 ± 35.79) μg/L, the indexes in patients with SAP were significantly higher than those in patients with MSAP, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that sPD-1 was positively correlated with sB7-H5 and TFF2 in patients with AP ( r = 0.552 and 0.641, P<0.01), and the sB7-H5 was positively correlated with TFF2 ( r = 0.610, P<0.01). The amylase, CRP, PCT, APACHE Ⅱ, SOFA, MCTSI, sPD-1, sB7-H5 and TFF2 in the dead patients were significantly higher than those in the living patients: (1 098 ± 105) U/L vs. (641 ± 93) U/L, (235.60 ± 40.17) mg/L vs. (118.04 ± 32.90) mg/L, (4.32 ± 0.52) μg/L vs. (3.14 ± 0.44) μg/L, (19.39 ± 3.14) scores vs. (11.18 ± 2.53) scores, (12.13 ± 2.78) scores vs. (7.40 ± 2.15) scores, (7.12 ± 1.73) scores vs. (4.31 ± 1.52) scores, (222.23 ± 22.30) ng/L vs. (171.14 ± 18.50) ng/L, (3.37 ± 0.89) μg/L vs. (2.59 ± 0.59) μg/L and (629.27 ± 39.63) μg/L vs. (560.78 ± 30.45) μg/L, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that CRP, PCT, APACHE Ⅱ, SOFA, sPD-1, sB7-H5 and TFF2 were independent risk factors death of in patients with AP ( OR = 1.339, 1.416, 1.285, 1.327, 1.092, 1.171 and 1.080; 95% CI 1.145 to 1.566, 1.146 to 1.751, 1.132 to 1.460, 1.150 to 1.531, 1.024 to 1.164, 1.072 to 1.280 and 1.031 to 1.131; P<0.01). The ROC curve analysis result showed that the area under the curve of sPD-1, sB7-H5 and TFF2 combined detection to predict the death in patients with AP was larger than that of sPD-1, sB7-H5, and TFF2 alone detection (0.870 vs. 0.771, 0.734 and 0.685). Conclusions:The increase of serum sPD-1, sB7-H5 and TFF2 levels in patients with AP is related to the severity of disease of patients with AP. The combined detection of the indexes can assist in evaluating the risk of death in patients with AP.
6.Analysis of the short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy
Yuwei ZHANG ; Zezhou LIU ; Yansong LIANG ; Enli CHEN ; Hongtao ZHANG ; Aixia SUI ; Juan WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(1):27-30
Objective:To analyze the influencing factors of short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy (RESCC). Methods:From January 2013 to March 2019, 47 patients (42 males, 5 females; age: 47-77 years) with RESCC who underwent CT guided 125I seed implantation in Hebei General Hospital were retrospectively analyzed. Patients were divided into effective group (complete remission (CR)+ partial remission (PR)) and ineffective group (stable disease (SD)+ progressive disease (PD)) according to response evaluation criteria in solid tumors (RECIST) at 3 months after implantation. Multivariate logistic regression was used to analyze the independent influencing factors of short-term efficacy. Cut-off values were determined by ROC curve. Results:Of 47 patients, 26 were effective (3 were CR and 23 were PR) and 21 were ineffective (7 were SD, 14 were PD). Multivariate regression analysis showed that tumor diameter, immediate postoperative dose delivered to 90% gross tumor volume ( D90), recurrence interval time were independent influencing factors of short-term efficacy (odds ratio ( OR; 95% CI): 4.240(1.220-14.737), 0.999(0.999-1.000), 0.989(0.979-1.000), Wald values: 5.163, 5.043, 3.956, all P<0.05). ROC curve showed that the AUC of tumor diameter, D90 and recurrence interval time were 0.782, 0.786 and 0.838 respectively, with cut-off values of 4.85 cm, 115.78 Gy and 297.5 d respectively. Conclusions:The short-term efficacy of 125I seed implantation for RESCC is mainly related to the tumor diameter, immediate postoperative D90 and recurrence interval time. Patients with tumor diameter <4.85 cm, immediate postoperative D90>115.78 Gy and recurrence interval time >297.5 d have better efficacy.
7.A multicenter study to develop and validate a novel C-GALAD Ⅱ HCC prediction model based on serological markers
Hongjiang LI ; Shaohui LIU ; Yongxiang YI ; Lijun DU ; Xiangchen LIU ; Hong SONG ; Lihua LIANG ; Wei WANG ; Guodong XIA ; Tianye JIA ; Aixia LIU ; Yanzhao LI ; Lida XU ; Boan LI
Chinese Journal of Laboratory Medicine 2022;45(11):1170-1176
Objective:To establish a model C-GALAD for detecting hepatocellular carcinoma (HCC) from the chronic liver disease and healthy people based on the serum markers.Methods:A clinical cohort including 229 hepatocellular carcinoma patients, 2 317 patients with chronic liver disease and 982 healthy people, was retrospectively collected from eight hospitals or physical examination institutions from April 2018 to October 2020. The data were divided into a training set and a testing set by stratified sampling with a 6∶4 ratio. A predictive model was established on the training set using a logistic backward regression method and validated on the testing set. In addition, clinical data from March to July 2021 in Beijing You′ an Hospital affiliated to Capital Medical University, including 84 patients with liver cancer and 204 patients with chronic liver disease collected were used for external independent validation of the model. The receiver operating characteristic curve (ROC) area under curve (AUC), the sensitivity and the specificity were used to evaluate the effectiveness of the model.Results:Through the logistic backward regression method, the seven signatures including age, gender, alpha-fetoprotein (AFP), alpha-fetoprotein alloplasm-3 ratio (AFP-L3%), des-gamma-carboxyprothrombin(DCP), platelet (PLT) and total bilirubin (TBIL) were selected as risk factors in the detection model. The area under the ROC curve (AUC) of the model on the testing set was 0.954, with an 88.04% sensitivity and a 94.85% specificity, and the AUC of model on the external independent validation set was 0.943, with an 89.29% sensitivity and a 90.2% specificity, which were better than other published models.Conclusion:The C-GALAD Ⅱ model can accurately predict the risk of hepatocellular carcinoma occurrence, and thus provide a trustworthy diagnosis method of hepatocellular carcinoma.
8.Clinical application of domestic recombinant human follicle-stimulating hormone in controlled ovarian hyperstimulation with assisted reproductive technology
Rui YANG ; Xiaoyan LIANG ; Yimin ZHU ; Yanping LI ; Dongzi YANG ; Feiyang DIAO ; Ping YIN ; Tingting LI ; Aixia LIU ; Yumei LI ; Lin LI ; Jing WANG ; Huangguo XIONG ; Rong LI
Chinese Journal of Reproduction and Contraception 2021;41(2):113-119
Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.
9.Clinical application of domestic recombinant human follicle-stimulating hormone in controlled ovarian hyperstimulation with assisted reproductive technology
Rui YANG ; Xiaoyan LIANG ; Yimin ZHU ; Yanping LI ; Dongzi YANG ; Feiyang DIAO ; Ping YIN ; Tingting LI ; Aixia LIU ; Yumei LI ; Lin LI ; Jing WANG ; Huangguo XIONG ; Rong LI
Chinese Journal of Reproduction and Contraception 2021;41(2):113-119
Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.
10. Factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors of head and neck
Enli CHEN ; Hongtao ZHANG ; Zezhou LIU ; Jinxin ZHAO ; Ke XU ; Yansong LIANG ; Aixia SUI ; Juan WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(2):93-97
Objective:
To analyze the factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck.
Methods:
A total of 73 patients (61 males, 12 females; age: (59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by 125I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled. The implanted seeds activity was 11.1-29.6 MBq, and the prescription dose was 80.0-145.0 Gy. CT examination was conducted 3 months after 125I seeds implantation. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, short-term efficacy was classified as effective (complete remission (CR), partial remission (PR)) and ineffective (stable disease (SD), progressive disease (PD)). Univariate analysis of factors affecting short-term effect (gender, age, history of radiation therapy, Karnofsky performance status (KPS) scores, pathological type, the longest diameter of tumor, implantation patterns, seeds activity, immediate postoperative dose delivered to 90% gross tumor volume (


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