1.Free thin sensate superficial circumflex iliac artery perforator flap based on lateral cutaneous branch of the subcostal nerve for repair of soft tissue defect in the foot and ankle
Zhaohui PAN ; Shan XUE ; Yuxiang ZHAO ; Hongfei LI ; Peng GAO ; Jianbo WANG ; Xingbo LI ; Jianli WANG
Chinese Journal of Trauma 2021;37(6):526-531
Objective:To investigate the efficacy of free thin sensate superficial circumflex iliac artery perforator flap based on lateral cutaneous branch of the subcostal nerve for repair of soft tissue defect in the foot and ankle.Methods:A retrospective case series study was made on clinical data of 9 patients with soft tissue defect in the foot and ankle admitted to 80th Group Military Hospital from December 2017 to December 2019. There were 8 males and 1 females, with the age of 28-63 years [(47.3±12.3)years] and the body mass index (BMI) of 16.7-27.8 kg/m 2 [(23.9±3.9)kg/m 2]. The size of soft tissue defect ranged from 10 cm×6 cm to 20 cm×12 cm. All patients were treated with the free thin sensate superficial circumflex iliac artery perforator flap based on lateral cutaneous branch of the subcostal nerve. After debridement or tumor resection, a thin sensate flap was harvested by intra-adipose tissue dissection between the superficial and deep fat layers. The size of flap ranged from 13 cm×8 cm and 13 cm×10 cm. The thickness of the defatted flap ranged from 3-6 mm. The distance from the anterosuperior iliac spine to the point where the lateral cutaneous branch of the subcostal nerve crossed the iliac crest ranged from 7.5-10.0 cm. The flap survival, complications, and reoperation were observed after operation. The sensory recovery of the flap was evaluated using Tinel sign and nine-grid method including monofilament touch perception, vibration perception, pinprick perception, temperature perception, and static two-point discrimination test. The joint range of motion, and shoewear and walking problems were recorded. At the last follow-up, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used to assess the affected foot and ankle. The injury at the donor site was detected as well. Results:All patients were followed up for 6-35 months [(21.1±10.1)months]. All flaps survived without infection or tumor reoccurrence. One patient developed ulceration, then surplus skin on the reconstructed heel was resected. One patient underwent flap debulking and removal of internal fixation. One or more sensory modalities within the nine areas in each flap could be detected at postoperative 3-6 months. The monofilament touch, vibration, pinprick, and temperature perception were presented in almost all regions of each flap at postoperative 12 months. However, only one patient in one region was noted with the static two-point discrimination, in which the distance of the two points was set as 25 mm. The range of ankle motion was slightly limited in 2 patients who underwent osseoligamentous complex reconstruction. All patients were able to wear normal shoes and walk without pain. At the last follow-up, the AOFAS ankle-hindfoot score ranged from 78 to 97 points [(86.4±7.4)points], significantly improved from preoperative 10-70 points [(44.2±18.4)points] ( P<0.01). No patients complained of pain at the donor site, but the widening linear scar was noted. Conclusion:For medium-sized soft tissue defect of the foot and ankle, the free thin sensate superficial circumflex iliac artery perforator flap based on lateral cutaneous branch of the subcostal nerve can be defatted with the requirement and has advantages in defect site appearance, sensory restoration, wearing ordinary shoes, painless walking, good functional recovery, and minimal donor site morbidity.
2.Effects of phlegm-resolving and stasis-removing herbal drugs on PGC-1α mRNA expressions and insulin resistance in NAFLD rats
Jianli GUO ; Shuai LU ; Chenxu LIU ; Yu LIU ; Xue HAN ; Lei HAO ; Yixin ZHANG
International Journal of Traditional Chinese Medicine 2019;41(3):252-257
Objective To explore the mechanism of phlegm-resolving and stasis- removing herbals on NAFLD by observing expressions of PGC1α mRNA and insulin resistance. Methods A total of 60 male SD rats were randomly divided into the normal group, model group, positive medication control group, high-dose, middle-dose and low-dose group. The rats were fed with high-fat forage for 8 weeks. The positive medication control group were gavaged with Dongbao-Gantai liquid (0.9 g/kg/day), the high-dose, middle-dose and low-dose group were gavaged with Xiaotan-Huayu liquid (43.34、32.50、21.67 g/kg/day), and normal group, model group were gavaged with equal volume of distilled water. The drugs were given by 1 ml/100 g and last for 8 weeks. The levels of TC, TG, FFA, ALT, AST, FBG, FINS, and HOMA-IR in serum, and levels of TC, TG, and PGC-1α mRNA and pathological morphological changes in hepatic tissue were observed after 8 weeks. Results The levels of TG (0.55 ± 0.10 mmol/L, 0.58 ± 0.09 mmol/L, 0.67 ± 0.11 mmol/L vs. 1.18 ± 0.15 mmol/L), TC (1.48 ± 0.24 mmol/L, 1.69 ± 0.27 mmol/L, 1.74 ± 0.27 mmol/L vs. 3.29 ± 0.26 mmol/L), FFA (251.08 ± 48.18 μmol/L, 277.53 ± 56.73 μmol/L, 291.82 ± 48.67 μmol/L vs. 432.19 ± 67.83 μmol/L), ALT (29.32 ± 4.17 U/L, 31.26 ± 4.74 U/L, 33.56 ± 5.18 U/L vs. 47.21 ± 8.67 U/L), AST (11.05 ± 2.18 U/L, 12.15 ± 2.67 U/L, 12.96 ± 2.93 U/L vs. 19.43 ± 3.68 U/L), FBG (5.68 ± 1.22 mmol/L, 6.86 ± 1.36 mmol/L, 7.94 ± 1.82 mmol/L vs. 11.88 ± 2.54 mmol/L), FINS (8.48 ± 1.22 mmol/L, 9.55 ± 1.95 mmol/L, 9.96 ± 1.74 mmol/L vs. 12.96 ± 2.67 mmol/L), HOMA-IR (1.91 ± 0.26, 2.91 ± 0.65, 3.52 ± 0.58 vs. 6.89 ± 1.21) in serum of high-dose, middle-dose and low-dose groups were decreased than model group. Levels of FFA (242.19 ± 35.13 μmol/L, 259.78 ± 29.33 μmol/L, 277.62 ± 34.29 μmol/L vs. 436.48 ± 52.15 μmol/L), TG (23.65 ± 3.28 mmol/L, 24.41 ± 3.15 mmol/L, 25.37 ± 3.59 mmol/L vs. 15.98 ± 2.37 mmol/L), TC (7.15 ± 0.82 mmol/L, 8.60 ± 0.95 mmol/L, 8.86 ± 1.04 mmol/L vs. 36.98 ± 4.28 mmol/L) were in hepatic tissue of high-dose, middle-dose and low-dose groups were significantly lower than the model group. The levels of PGC-1α mRNA (1.24 ± 0.06, 1.02 ± 0.07, 0.99 ± 0.08 vs. 0.43 ± 0.06) in hepatic tissue of high-dose, middle-dose and low-dose groups were significantly higher than model group. Conclusions The phlegm-resolving and stasis-removing herbals may improve lipid metabolism by regulating the expression of PGC-1α mRNA, inhibiting gluconeogenesis and liver sugar output, correcting disturbance of lipid metabolism and improving insulin resistance.
3.Effects of Ginsenoside Rb1 in Different Dosages on Spinal Cord Ischemia-reperfusion Injury and Expression of Survivin in Rats
Bin CHENG ; Huanjin SONG ; Fengtao LI ; Lei LIN ; Jianli XUE ; Hao WU ; Jintao YE
Chinese Journal of Rehabilitation Theory and Practice 2018;24(5):520-525
Objective To observe the effects of different dosages of ginsenoside Rb1 preconditioning on spinal cord ischemia-reperfusion injury in rats, and the possible mechanism. Methods Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12), and 10 mg/kg (D10, n=12), 20 mg/kg (D20, n=12), 40 mg/kg (D40, n=12) and 80 mg/kg (D80, n=12) drug groups. Spinal cord ischemia for ten minutes and reperfusion model was established, and the drug groups were injected ginsenoside Rb1 intraperitoneally in their dosages 30 minutes before modeling. They were assessed with BBB score 48 hours after reperfusion, and then were sacrificed for HE staining, TUNEL staining and immunohistochemistry staining of survivin.Results The BBB score was more in the drug groups than in the model group (P<0.05), and was the most in D40 and D80 groups. The expression of survivin was more in the drug groups than in the model group (P<0.05), and was the most in D40 and D80 groups. The apoptosis of neurons was less in the drug groups than in the model group (P<0.05), and was the least in D40 and D80 groups.Conclusion The ginsenoside Rb1 could promote the expression of survivin, inhibit apoptosis of neurons, to protect the neural function, in dose-dependent manner somehow.
4.Evaluation of left and right atrial synchrony in patients with sick sinus syndrome before and after pacemaker implantation by tissue Doppler ultrasonography
Xue FENG ; Min LU ; Maohui ZHANG ; Jianli REN ; Haitao RAN ; Zhigang WANG
Chinese Journal of Ultrasonography 2017;26(12):1013-1017
Objective To evaluate the intra- and interatrial synchronization before and after pacemaker implantation in patients with sick sinus syndrome ( SSS) by tissue Doppler imaging ( TDI) . Methods Thirty-eight patients with SSS ( SSS group ) underwent pacemaker implantation . Echocardiography was performed before and after operation . Twenty-five volunteers were chosen as control group . Routine measurement of left and right atrial diameter by echocardiography . In apical four chamber view ,the sample volume of TDI was located at right atrial lateral wall at tricuspid annulus ,interatrial septum and left atrial lateral wall at mitral annulus . The interval time between the early diastolic wave ( E wave) and the late diastolic wave (A wave) (E-AR ,E-AI ,E-AL ) ,and the duration of A wave (AR ,AI ,AL ) were measured . At the same time ,the electromechanical coupling time was measured ,namely the initiation of the P wave of the synchronous electrocardiogram to the starting point of A wave ( P-A0R ,P-A0I ,P-A0L ) , and the starting point of the P wave to the peak point of the A wave ( P-AR ,P-AI ,P-AL ) . And the right atrial electromechanical delay time ,P-A0I and P-A0R value ( T0IR ) ,P-AI value and P-AR value ( TIR ) were recorded .Other parameters include left atrial electromechanical delay time:P-A0L and P-A0I value ( T0LI ) , and P-AL and P-AI value ( TLI ) ;interatrial electromechanical delay time:P-A0L and P-A0R value ( T0LR ) ,P-AL and P-AR ( TLR ) were recorded . Results Compared with the control group ,left atrium and right atrium in SSS group enlarged before operation , E-AR ,E-AI ,E-AL ,P-A0R ,P-A0I ,P-AR ,P-AL prolonged ,while T0LR and T0LI were shortened ( all P < 0 .05 ) . Postoperative changes in SSS group patients included shortened E-AR ,E-AI and E-AL ,and prolonged T0LI and T0LR ( all P <0 .05) . Compared with the control group ,the size of left atriums and right atriums in SSS group still increased postoperation ,and the P-A0I 、P-AR and P-AL remained longer (all P <0 .05) . The same as the control group ,the postoperative AR ,AI and AL in SSS group were decreased successively ( all P < 0 .05 ) . Conclusions In SSS patients , electromechanical asynchrony exists in different part of atrium and between left atrium and right atrium . Pacemaker therapy can improve atrial electromechanical synchronicity .
5.Clinical application of hepatic gallbladder puncture drainage under CT guide in emergency
Zhanli ZHANG ; Xinwei HAN ; Weidi WANG ; Lijun HE ; Dong LI ; Jianli WANG ; Nan XUE
Journal of Practical Radiology 2016;32(8):1275-1276,1281
Objective To explore the clinical application and value of percutaneous transhepatic gallbladder drainage (PTGD)under CT guide in high-risk emergency.Methods In all 57 old patients with high-risk acute cholecystitis in emergency,cuff-PTGD in 39 was performed and fractional step PTGD in 18 was also used.Results PTGD was successfully in all patients.After PTGD,except for 1 patient died of severe cardiac insufficiency,the abdominal pain and fever were alleviated during 72 hours,and the complications was not demonstrated.Conclusion As a safe,noninvasive and accurate method,CT-guided PTGD may relieve symptoms quickly,reduce the mortality and improve the treatment for some old patients with high risk acute cholecystitis.
6.Effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in developing rats
Jianli LI ; Honghai WU ; Wei LIANG ; Gai XUE ; Yang YU ; Yanning HOU
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(7):584-587
Objective To investigate the effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in neonatal rats.Methods 80 SD male rats aged 7 days were randomly divided into group C,V,E,K and K+E,and 16 per group.Group C was intraperitoneally injected with same volume of saline for three consecutive days,Group V was subcutaneously injected with same volume of sesame oil for three consecutive days,Group E was subcutaneously injected with 600 μg · kg-1 17β-estradiol for three consecutive days,group K was intraperitoneally injected with 75 mg · kg-1 ketamine for three consecutive days,group K+E was intraperitoneally injected with 75 mg · kg-1 ketamine in combination with 600 μg · kg-1 17β-estradiol injected subcutaneously for three consecutive days.At 2 months of age,learning and memory abilities were tested with the Mortis water maze.After Morris water naze test,ten rats from each group were decapitated and the prefrontal cortex (PFC) was isolated to detect acetylcholine esterase(AchE) activity with ELISA assay and to measure acetylcholine(Ach) level by hydroxylammonium chloride method.Results The escape latency ((40.26±2.36) s,(30.25±2.20) s,(21.55±2.42) s) and path length((1019.35±58.13) cm,(811.16±27.58) cm,(598.34±34.74) cm) of group K were more than those of group C on the third,fourth aud fifth training days (all P<0.05),while escape latency ((29.46±2.20) s,(24.86± 2.14) s,(17.20±1.91) s) and path length((913.90±41.89) cm,(729.42±31.36) cm,(487.64±18.61)cm) of group K+E were significantly lower than those of group K(all P<0.05).On test day 6,rats were subjected to a probe trial,ratio of time spent in the target quadrant ((24.5±2.7) %) and the number of crossings over previous platform locations (1.9±0.5) in group K were fewer than those of group C (all P<0.05),while ratio of time spent iu the target quadrant((42.3±3.0) %) and the number of crossings over previous platform locations(3.5±0.5) of group K+E were more than those of group K (all P<0.05).The AchE activity((0.69±0.04) U · mg pro-1) in rats PFC of group K was significantly higher than that of group C ((0.52±0.06) U · mg pro-1) (P<0.05).The AchE activity of group K +E ((0.58±0.12)U · mg pro-1) was lower than that of group K(P<0.05).The Ach level ((2.59±0.34)mg · g-1) in rats PFC of group K was significantly lower than that of group C ((4.35±0.56) mg · g-1) (P<0.05).The Ach level of group K+E((3.88±0.61) mg · g-1) was higher than that of group K(P<0.05).Conclusions These results indicate that ketamine impairs learning and memory abilities as rat matures,while 17β-estradiol treatment improves these impairments by inhibiting AchE activity and increasing Ach level.
7.In vivo tracking of PKH26-labeled human umbilical cord mesenchymal stem cells after transplantation into rats with liver cirrhosis.
Gai XUE ; Jianli LI ; Jianfang LIU ; Honghai WU ; Yanning HOU
Chinese Journal of Hepatology 2014;22(12):910-914
OBJECTIVETo observe the in vivo migration of human umbilical cord mesenchymal stem cells (hUCMSCs) labeled with the PKH26 red fluorescent dye after transplantation into rats with liver cirrhosis.
METHODSFrozen hUCMSCs were resuscitated and labeled with PKH26. Labeling efficiency and fluorescent maintenance time of the PKH26-1abeled cells were measured. Morphology of the labeled and unlabeled (control) cells was observed by microscopy. The cell growth curve was determined using the MTT method. The PKH26-1abeled hUCMSCs were transplanted via tail vein injection into healthy (control) rats and rats with liver cirrhosis. Migration of the PKH26-1abeled hUCMSCs observed 48 h later in frozen liver sections under a fluorescence microscope.
RESULTSThe labeling ratio of PKH26 to hUCMSCs was 100%. Growth of the labeled cells was good. The cell morphology was not significantly different between the labeled and unlabeled cells; all cells were long and spindle-like. Cell proliferation was not impacted significantly by labeling.Fluorescence was maintained for at least 20 days, as detected by in vitro analysis. After transplantation into the rats, the PKH26-1abeled hUCMSCs were mainly distributed in the area surrounding the portal vein, the blood vessels, and the false lobule of the cirrhotic liver; a small amount ofhUCMSCs were present in the spleen and lung.
CONCLUSIONPKH26 is an ideal fluorescent dye to label hUCMSCs. The PKH26 labeling technique can be used to study the migration of hUCMSCs in cirrhotic liver.
Animals ; Cell Proliferation ; Fluorescent Dyes ; Humans ; Liver Cirrhosis ; Mesenchymal Stromal Cells ; Organic Chemicals ; Rats ; Umbilical Cord
8.Clinical features and risk factors analysis of acute graft-versus-host disease in patients with related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation.
Wenjing XUE ; Urumqi 830054, CHINA. ; Ming JIANG ; Urumqi 830054, CHINA. ; Meng TIAN ; Urumqi 830054, CHINA. ; Xianlin DUAN ; Urumqi 830054, CHINA. ; Jianhua QU ; Urumqi 830054, CHINA. ; Hailong YUAN ; Urumqi 830054, CHINA. ; Jianli XU ; Urumqi 830054, CHINA. ; Bingzhao WEN ; Urumqi 830054, CHINA. ; Ling LI ; Urumqi 830054, CHINA. ; Yichun WANG ; Urumqi 830054, CHINA. ; Ying LIU ; Urumqi 830054, CHINA. ; Xinyou WANG ; Urumqi 830054, CHINA. ; Haizhou CAO ; Urumqi 830054, CHINA.
Chinese Journal of Hematology 2014;35(12):1100-1106
OBJECTIVETo study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT).
METHODSFrom July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period.
RESULTS(1)The cumulative incidence of aGVHD in the RHNT-PBSCT group was significantly higher than the MSNT-PBSCT group [(56.2±4.7)% vs (34±3.6)%, P<0.05], but the cumulative incidences of II-IV and III-IVgrade aGVHD had no significant difference between the two groups[(39.5±2.9)% vs (21.2±5.4)%, P>0.05; (12.6±4.1)% vs (10.8±2.4)%, P>0.05]. (2)The cumulative incidence of cutaneous aGVHD was significantly higher in RHNT-PBSCT group than that in MSNT-PBSCT group [(42.3±3.2)% vs (17.5±2.3)%, P<0.05]. The cumulative incidences of liver and gastrointestinal aGVHD between the two groups had no significant difference [(7.7±2.1)% vs (12.6±3.4)%, P>0.05; (16.3±4.5)% vs (10.3±2.5)%, P>0.05]. (3)The 3-year disease free survival (DFS) and overall survival(OS) of RHNT-PBSCT group and MSNT-PBSCT group were (63±5.5)%, (65.2±4.7)% and (74.2±5.4)%, (77.4±5)% respectively, without significance (P=0.078, P=0.052). (4)aGVHD occurrence with HLA haplotype (P=0.003) and matched loci (P=0.002) were significantly correlated by univariate analysis. Multivariate analysis showed that only the HLA typing is a risk factor for aGVHD (HR=1.891, P=0.03).
CONCLUSIONAlthough the incidence of total aGVHD in RHNT-PBSCT protocol is higher than that in MSNT-PBSCT, but there was no significance in severe aGVHD and cutaneous aGVHD was the common type, which indicates that RHNT-PBSCT protocol is feasible.
Disease-Free Survival ; Graft vs Host Disease ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Humans ; In Vitro Techniques ; Incidence ; Peripheral Blood Stem Cell Transplantation ; Risk Factors ; Siblings ; T-Lymphocytes
9.Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells induced by liver homogenate supernatants
Xin MA ; Gai XUE ; Jianfang LIU ; Jianli LI ; Yanning HOU
Chinese Journal of Tissue Engineering Research 2013;(45):7877-7884
BACKGROUND:Preliminary experiments have demonstrated that rat liver homogenate supernatants can induce the morphological changes of human umbilical cord mesenchymal stem cells. However, little is known about whether the induced cells have some phenotypic and functional features of hepatocytes.
OBJECTIVE:To investigate whether human umbilical cord mesenchymal stem cells have some phenotypic and functional characteristic of hepatocytes after being induced by liver homogenate supernatants.
METHODS:Passage 3 human umbilical cord mesenchymal stem cells were used and divided into control group (cells were cultured in basic culture medium) and liver homogenate supernatant group (cells were cultured in liver homogenate supernatants for 3, 5, 7 days). Meanwhile, positive control group (QSG-7701 human liver celllines) and negative control group (simple liver homogenate supernatants) were set up. The protein and mRNA level of hepatocyte markers, alpha-fetoprotein, cytokeratin 18 and tryptophan 2,3-dioxygenase enzyme, were detected at different time points.
RESULTS AND CONCLUSION:After inducement, the stem cells of fusiform shape began to lose their sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with the morphous of triangle, polygon and anomalism shape. Compared with the control group, the protein and mRNA level of alpha-fetoprotein, cytokeratin 18 and tryptophan 2,3-dioxygenase enzyme significantly increased time dependently after inducement with liver homogenate supernatants (P<0.01). This study demonstrated that human umbilical cord mesenchymal stem cells are able to differentiate into hepatocyte-like cells in vitro that possess some functions of liver cells.
10.Anterolateral thigh perforator flap bridging superficial circumflex iliac artery flap for the treatment of complex limb wound
Zhaohui PAN ; Jianli WANG ; Pingping JIANG ; Hongfei LI ; Shan XUE ; Yuxiang ZHAO
Chinese Journal of Orthopaedics 2013;(7):723-730
Objective To investigate the application and clinical outcomes of anterolateral thigh perforator flap bridging different superficial circumflex iliac artery flaps for the treatment of complex limb wound.Methods Data of 10 patients,who had undergone free tissue transfer of anterolateral thigh perforator flap bridging different superficial circumflex iliac artery flaps (iliac osteocutaneous flap,iliac crest flap and ilioinguinal flap) for the complex limb wound from March 2009 to January 2011,were retrospectively analyzed.There were 9 males and 1 female,aged from 21 to 57 years (average,39.7 years).Iliac osteocutaneous flap was used in 7 patients,iliac crest flap in 2 patients and ilioinguinal flap in 1 patient.The free tissue transfer was performed for hand reconstruction in 3 cases,foot reconstruction in 4 cases and leg reconstruction in 3 cases.The mean size of soft tissue defect was 20 cm × 9.7 cm.Results The mean size of the anterolateral thigh flap and the ilioinguinal flap was 17.8 cm×9.4 cm and 8.4 cm×4.5 cm,respectively.The mean volume of iliac crest was 5.4 cm×2.1 cm×0.8 cm,and the mean length of flow-through conduit was 10.5 cm.Except for the distal necrosis of iliac osteocutaneous flap in 1 case,which were treated by dressing change and skin grafting,the other flaps survived without complications.All patients were followed up for 6 to 36 months (average,12 months).The average bone union time was 3 months in the hand group,4 months in the foot group,and 4.5 months in the leg group.The disabilities of the arm,shoulder,and hand questionnaire score averaged 43,the mean Japanese Orthopaedic Association's foot rating scale was 71.3,and the mean Puno's functional score was 91.Donor site scars were mostly flat,pale and soft but widened in the thigh in 6 patients and in the ilioinguinal region in 3 patients,and numbness was reported in 2 patients.Conclusion In clinical situation that requires for coverage of complex and extensive limb defects,the free tissue transfer of anterolateral thigh perforator flap bridging superficial circumflex iliac artery flap is a better method,which can meet specific reconstructive demands with minimal donor site morbidity.However,a relative high risk has to be considered.

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