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OBJECTIVE@#To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions.@*METHODS@#Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms.@*RESULTS@#Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway.@*CONCLUSIONS@#We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.
Subject(s)
Female , Humans , Antigens, Neoplasm , Blood , Biomarkers, Tumor , Blood , Carrier Proteins , Blood , Case-Control Studies , Uterine Cervical Dysplasia , Blood , Diagnosis , Chromatography, Liquid , Complement Factor I , Early Detection of Cancer , Glycoproteins , Blood , Haptoglobins , Neoplasm Proteins , Blood , Orosomucoid , Precancerous Conditions , Blood , Diagnosis , Serum Albumin, Human , Tandem Mass Spectrometry , Uterine Cervical Neoplasms , Blood , DiagnosisABSTRACT
Purpose To investigate the value of contrast-enhanced ultrasound (CEUS) in monitoring hepatic parenchymal perfusion quantitatively during resuscitation after hemorrhagic shock (HS).Materials and Methods Forty-five labeled rabbits were randomly divided into five groups.One group was normal control group,and the other four groups were established reversible HS modes by using modified Wiggers method.In the four model groups,one group was chosen as the shock group,and the other three groups received colloid (hydroxyethyl starch) for resuscitation.The three resuscitation groups were named as 1 h group,4 h group,24 h group according to resuscitation time.The arterial blood was collected for testing blood lactic acid (LAC) in each group.The CEUS was performed to form time-intensity curve (TIC) for quantitative analysis.At the end of the experiment,the rabbits were sacrificed and the liver tissues were examined for pathology.Results Compared with the normal control group,the arrival time (AT) and time to peak (TTP) of the shock group were significantly prolonged,and the peak intensity (PI) and area under curve (AUC) of the shock group decreased,all with significant difference (all P＜0.05);in the 1 h resuscitation group,the PI and AUC increased,and the AT decreased,all with significant difference (all P＜0.05);in the 4 h and 24 h resuscitation group,the PI and AUC increased,and the AT and TTP decreased,but all without significant difference (all P＞0.05).Compared with the shock group,the PI and AUC of the 1 h resuscitation group increased,and the AT of 1 h resuscitation group decreased,all with significant difference (all P＜0.05);all the tested parameters of the 4 h and 24 h resuscitation group were significant different (P＜0.05).Conclusion CEUS can quantitatively evaluate the changes of hepatic parenchymal perfusion during HS resuscitation,which has a certain reference for clinical treatment.
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Purpose Contrast-enhanced ultrasound (CEUS) guided percutaneous puncture injection of hemostatic agents or biological glue is good for the control of closed renal trauma,but there are also some shortcomings.This study aims to explore the effect of CEUS guided percutaneous puncture injection of hemostatic agent and xanthan gum on the control of closed renal trauma hemorrhage.Materials and Methods Sixteen healthy white rabbits were established closed renal trauma models of active bleeding,and were randomly divided into two groups,puncture and laparotomy group.The puncture group was treated with CEUS guided percutaneous injection of snake venom enzyme and biological glue into the active renal hemorrhage.The laparotomy group was treated with traditional surgical suture.The therapeutic effect of two groups was evaluated after operation.The treatment time was recorded,and the renal function was measured every week after the operation.The pathological examination of the wound tissue was performed 1 month after operation.Results Two groups were successful hemostasis.The operation time of puncture group and open group was (179 ± 30) s and (298 ± 30) s,respectively,and the difference was statistically significant (P＜0.05).After operation,the serum creatinine of the puncture group was lower than that of the laparotomy group,and the difference was statistically significant (P＜0.05).The recovery of renal function of the puncture group was faster than that of the laparotomy group,and the renal wound healing was better than that of the laparotomy group.Conclusion The effect of CEUS guided percutaneous puncture injection of snake venom enzyme combined with biological glue in the treatment of closed renal trauma hemorrhage is good,which is a new method worth recommending for easy operation,small damage and quick recovery.
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Pttrpose Contrast-enhanced ultrasound (CEUS) is a noninvasive technique that can monitor the blood perfusion of organs.The study aims to discuss the value of CEUS in quantitative analysis of renal microcirculation during resuscitation after hemorrhagic shock (HS).Materials and Methods Forty healthy New Zealand white rabbits were randomly divided into five groups in this prospective study.One group was selected as normal control group (T1),the other four groups were established HS model by using the modified Wiggers's method;one of the four HS groups was taken as shock group (T2),and the other three HS groups were named as 2 h group (T3),6 h group (T4),and 24 h group (T5) according to resuscitation time.CEUS was used to observe the rabbits' renal perfusion and the perfusion parameters were recorded including amplitude of peak intensity (A),time to peak (TTP),area under curve (AUC) and curve rising slope rate (Grad);the correlation of these parameters with histological examination was analyzed.Results Compared with T1 group,The TTP ofT2 group prolonged and the A,AUC and Grad decreased (P＜0.05);the HS model was established successfully.Compared with T2 group,the A,AUC and Grad of T3,T4 groups increased (P＜0.05),but the TTP of T3,T4 groups was not shortened (P＞0.05).The above parameters were all significantly different between T5 group and T2 group (P＜0.05),but the differences did not exist between T5 and T1 groups (P＞0.05),which indicated that the perfusion parameters gradually returned to normal level after resuscitation.The histological staining demonstrated that the renal tubular epithelial cell swelling and vascular congestion gradually restored after resuscitation.Conclusion CEUS can quantitatively assess renal perfusion changes during resuscitation as a noninvasive monitor.
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Purpose To study the value of contrast-enhanced ultrasound (CEUS) quantitative technique in evaluating the perfusion of hepatic microcirculation in acute hemorrhagic shock (HS),and to investigate the value of CEUS quantitative analysis in HS diagnosis and treatment.Materials and Methods Sixty healthy adult New Zealand white rabbits of either gender were randomly divided into three groups for establishing mild,moderate and severe HS models,respectively.Before modeling and 30 min after stable modeling,liver CEUS examination was performed,and the original images were stored.Blood test of lactic acid,liver function,and liver biopsy for pathological examination were conducted after CEUS.Finally,the arrival time (AT),time to peak (TTP),rising time (RT),peak intensity (PI) and area under the curve (AUC) were analyzed offiine.Results Compared with pre-modeling,AUC decreased in mild HS group (P＜0.05);TTP and RT were delayed,but PI and AUC decreased in moderate and severe HS groups (all P＜0.05);AT was delayed in severe HS group (P＜0.05).The differences of TTP,RT,PI and AUC between the groups of mild,moderate and severe HS were significant (P＜0.05).Compared with pre-modeling,lactic acid in three HS groups increased significantly,the liver function indexes were changed to different degrees,and the degree of liver cell pathological changes was closely related to the degree of HS.Conclusion CEUS can quantitatively evaluate the changes of hepatic microcirculation induced by HS at different degrees.
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Purpose To study the effects of different doses of ultrasound contrast agent SonoVue upon contrast-enhanced ultrasound (CEUS) in the kidney of healthy rabbits, and to seek the optimal dose of SonoVue. Materials and Methods CEUS was performed in 10 healthy rabbits with GE LOGIQ-E9 by using 8 different doses of SonoVue (ranging from 0.02 ml/kg to 0.16 ml/kg). The quantitative parameters of the time-intensity curve (TIC) were measured and statistically compared. Results The TICs showed that the peak intensity (PI) and the area under curve (AUC) increased with dose when the doses ranged from 0.02 ml/kg to 0.10 ml/kg (r=0.962 and 0.965, P<0.05); when the dose further increased, AUC had little change but PI decreased reversely. The arrival time (AT) shortened along with the increase of the SonoVue dose (r= - 0.917, P<0.05). The dose had a positive correlation with time to peak (r=0.49, P<0.05). Conclusion The parameters of TIC are influenced intensely by different doses of SonoVue. It is important to realize the relationship between SonoVue doses and its effects upon contrast-enhancement ultrasound in microcirculatory quantification. The dose of 0.10 ml/kg appears to be the optimal dose for CEUS in examining kidney of healthy rabbit.
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PurposeThe monitor of organ microcirculation is significant in the diagnosis and treatment of hemorrhagic shock (HS). We established an HS experimental model and evaluated it by contrast-enhanced ultrasound (CEUS), which aimed to evaluate the value of CEUS and time-intensity curve (TIC) in quantitative analysis of renal cortical microcirculation.Materials and Methods The experimental models of HS were established in 30 healthy New Zealand white rabbits by controlled exsanguinations and were divided into four groups according to the shock grade: normal (100% MAP), mild (70% MAP), moderate (50% MAP) and severe (40% MAP). The right kidneys of the experimental model were examined by CEUS. The corresponding parameters of the TIC such as arrival time (AT), time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were measured with the TIC analysis software package when the region of interest was set in superficial of renal cortex.Results The model of HS were successfully established with 30 healthy New Zealand rabbits. Twenty-seven healthy New Zealand rabbits were alive at the end of the experiment, and three died of severe shock. The TIC rose steeply and reached the peak quickly, and then declined slowly to the baseline, which reflected the transition of microbubble in the region of interest. As the hemorrhagic shock model progressed from normal to mild, PI and AUC gradually decreased and the differences were significant (P0.05). AT and TTP gradually prolonged compared with normal and mild shock groups, and the differences were significant (P<0.05).Conclusion CEUS and TIC can quickly and accurately assess the renal perfusion changes of acute hemorrhagic shock model of animals in a quantitative way. It can be used as a new noninvasive monitoring tool in quantitative analysis of renal cortical microcirculation.