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1.
The purpose of this study was to compare the assessment of functional severity on in-vivo hepatic 31P-MRS in diffuse hepatic disease with functional severity assessed with 99mTc galactosyl serum albumin (99mTc-GSA). 31P-MRS was performed in 10 healthy control subjects and 16 patients with diffuse hepatic disease. Data were expressed as peak area ratios: PME/beta-ATP, PDE/beta-ATP, PME/PDE, Pi/beta-ATP, and PME/Pi. The functional severity of hepatic damage was evaluated visually and quantitatively (HH15, LHL15) by 99mTc-GSA in the group of patients with diffuse hepatic disease. Visual evaluation was classified into four grades based on anterior images of cardiac blood-pool and liver. We studied the correlation of spectral metabolic ratios and functional severity by 99mTc-GSA. We found statistically significant differences (ANOVA) among the classifications of Grade I, Grade II, and Grade III with both PME/beta-ATP and PME/PDE. A statistically significant direct correlation was found between HH15 and both PME/beta-ATP and PME/PDE. A significant inverse correlation was also seen between LHL15 and both PME/beta-ATP and PME/PDE. The studies comparing 31P-MRS with functional severity assessed by 99mTc-GSA showed that PME/beta-ATP and PME/PDE were useful for the assessment of functional severity in patients with diffuse hepatic disease.  相似文献   

2.
MRI及31P-MRS在脂质沉积性肌病中的诊断   总被引:1,自引:0,他引:1  
目的:应用磁共振成像(MRI)及磷频谱(31P-MRS)评价脂质沉积性肌病(LSM)的影像表现,探讨其临床应用价值.方法:对经病理证实的6例LSM和17例健康对照者进行MRI及31P-MRS检查.结果:6例LSM患者大腿后组肌群和内侧肌群T1 WI及T2 WI上均表现为多发小斑点状高信号,T2 WI抑脂后信号减低;LSM组PCr(磷酸肌酸)、PCr/ATP(三磷酸腺苷)和磷酸化能力(PP)较对照组明显降低(P<0.05),二磷酸腺苷(ADP)、Pi(无机磷)、Pi/ATP、Pi/PCr较对照组明显增高(P<0.05),PH与对照组无明显差别(P=0.6395).结论:MRI联合31P-MRS检查有利于LSM的诊断、鉴别诊断.  相似文献   

3.
磁共振动态磷谱对正常人骨骼肌运动状态功能的定量研究   总被引:3,自引:1,他引:2  
目的用磁共振动态磷谱技术(31P-MRS)无创性在体评价骨骼肌的功能。资料与方法对10名成年人和6名青少年受试者骨骼肌进行动态31P-MRS分析,对磷酸单酯(PME)、无机磷(Pi)、磷酸二酯(PDE)、磷酸肌酸(CP)、γ-ATP、α-ATP和β-ATP进行半绝对定量分析,同时计算二磷酸腺苷(ADP)和线粒体内氧化磷酸化潜能(PP)以及细胞内镁离子的浓度。分析在静息期、运动期和恢复期两组受试者能量代谢特点及肌肉做功效率。结果肌肉运动时CP和PP含量明显降低,Pi、Pi/CP和ADP升高,而ATP维持恒定。青少年肌细胞内ATP明显高于成人,而CP和PP含量相似,动态变化趋势相同。成人做功较多,但肌肉的效率与青少年组相同。结论动态磷谱技术可以无创性定量评价骨骼肌不同运动状态能量代谢特点,为肌肉的功能影像学提供客观信息。  相似文献   

4.
Phosphorus-31 liver spectra were recorded from 6 controls and 12 patients with liver disease using TR values of 0.5 and 5 s and a pulse angle of 45 degrees. One of the control subjects was also examined at seven TR values ranging from 0.5 to 20 s. Spectra from one additional patient were collected at TRs of 0.5, 1, and 2 s only. There was a significant increase in the mean ratio of peak areas phosphomonoesters (PME)/beta-ATP in 9 of the 13 patients and a decrease in phosphodiesters (PDE)/beta-ATP in 3 of the patients, compared with controls, at the longer TR values. The saturation factors for PME and PDE were greater than those for Pi and beta-ATP, and spectral abnormalities in disease were often more evident as the TR value was increased from 0.5 to 5 s. Acquisition parameters need to be chosen with a knowledge of the impact that saturation effects have on metabolite quantification and spectral contrast.  相似文献   

5.
目的分析不同年龄组骨骼肌能量代谢特点。方法对10例成年人和6例青少年受试者进行31P MRS分析,对磷酸单酯(PME)、无机磷(Pi)、磷酸二酯(PDE)、磷酸肌酸(CP)、γ-ATP、α-ATP和β-ATP的峰下面积进行半绝对定量分析,同时间接计算二磷酸腺苷(ADP)和线粒体内氧化磷酸化潜能(PP)以及细胞内pH值和镁离子的浓度。比较2组受试者能量代谢相关化合物的含量。结果正常成年人(青少年)每千克骨骼肌内CP和总ATP含量分别为24.76(25.52)mmol和18.38(21.36)mmol。与成人相比,青少年ATP含量较高,PDE含量较低。pH值、镁合ATP及总镁离子含量青少年组均明显高于成人组。而Pi、CP、ADP、PP、自由镁离子和游离ATP的含量2组间无显著性差异。结论31P-MRS可无创探测细胞内能量代谢特点。  相似文献   

6.
Injection of iodized oil (Lipiodol) into the hepatic artery is widely used in the diagnosis and treatment of hepatocellular carcinoma. However, no reports have yet appeared concerning temporal changes in hepatic metabolism following Lipiodol injection. In the present study, Lipiodol was injected into the hepatic arteries of normal and cirrhotic rats, successive P-31 MR measurements were performed, and temporal changes in metabolism were compared with histologic findings. Both normal and cirrhotic rats displayed minimum levels of beta-ATP/PME and beta-ATP/Pi 5 days after hepatic arterial injection of Lipiodol. However, 10 days after injection these values had reverted to the preinjection levels. The metabolic dysfunction observed in the liver following hepatic arterial injection of 0.3 ml/kg b.w. Lipiodol was transient. Moreover, no distinct differences were observed between P-31 MR changes in normal and cirrhotic rats. Conversely, histologic impairment assessed on the basis of hepatic necrosis ratios was most severe 2 days after hepatic arterial injection in both normal and cirrhotic rats, and this did not coincide with the time of the most pronounced metabolic impairment as inferred from P-31 MR changes.  相似文献   

7.
31P NMR was used to measure the concentrations and spin-lattice relaxation times of phosphorus-containing metabolites in neocartilage developing in an NMR-compatible hollow-fiber bioreactor over four weeks. Separate studies were performed for tissue developing from chondrocytes taken from the proximal and the distal sternum of the chick embryo. The metabolite ratio beta-ATP/Pi did not change significantly with development (proximal: beta-ATP/Pi = 0.38+/- 0.12 at one week, beta-ATP/Pi = 0.44+/-0.07 at four weeks, P< 0.63; distal: beta-ATP/Pi = 0.39+/-0.05 at one week, beta-ATP/Pi = 0.66+/- 0.26 at four weeks, P<0.28). ATP spin-lattice relaxation times were found to be comparable to those in muscle and brain tissue (proximal: T(1)(beta-ATP) = 0.5+/-0.06 sec at one week, T(1)(beta-ATP) = 0.4+/- 0.01 sec at four weeks; distal: T(1)(beta-ATP) = 0.3+/-0.12 sec at one week, T(1)(beta-ATP) = 0.4+/-0.04 sec at four weeks). A large increase in the spin-lattice relaxation time of inorganic phosphate, from 1.2+/-0.13 sec to 3.8+/-0.04 sec (P<0.0001) over four weeks of growth, was observed in tissue developing from chondrocytes harvested from the proximal sternum. No comparable increase in T(1)(Pi) was found in tissue developing from chondrocytes harvested from the distal portion of the sternum, which ossifies later in vivo.  相似文献   

8.
RATIONALE AND OBJECTIVES. Hepatic embolization combined with intra-arterial administration of cytostatic drugs (chemoembolization) is frequently used to treat primary and metastatic cancers to the liver. Quantitative phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to assess the metabolic state of hepatic cancers and their metabolic response to chemoembolization. METHODS. Fifteen localized 31P MRS studies were performed on five patients with liver tumors. Thirteen healthy volunteers served as controls. Metabolite ratios and molar metabolite concentrations were calculated. RESULTS. Untreated hepatic tumors, relative to normal controls, showed elevated phosphomonoester/adenosine triphosphate (PME/ATP) ratios, reduced concentrations of ATP and inorganic phosphate (Pi), and normal phosphodiester (PDE) concentrations. As an acute response to chemoembolization, ATP, PME, and/or PDE concentrations diminished, whereas Pi concentrations increased or stayed relatively constant. Long-term follow-up after chemoembolization showed decreased PME/ATP and increased ATP concentrations in the absence of changes on standard magnetic resonance and computed tomographic images. CONCLUSIONS. These preliminary spectroscopic data suggest that quantitative 31P MRS can be successfully used to monitor directly metabolic response to hepatic chemoembolization.  相似文献   

9.
Changes in metabolic state of the liver after intravenous fructose (250 mg/kg) load were evaluated by P-31 MR spectroscopy. Study was performed in eight healthy volunteers and six patients with liver cirrhosis. In the spectra of the cirrhotic livers the fructose load caused no significant increase in PME peak, which suggested that fructose metabolism of the cirrhotic livers had impediments before the fructose-1-phosphate stage. Also shown in the spectra of the cirrhotic livers was the significant drop of Pi, PDE, and ATP peaks. This might reflect the low concentration of Pi, PDE and ATP in the cirrhotic livers.  相似文献   

10.
The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment.  相似文献   

11.
The current study tested the concept that cine magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy might be used to provide a comprehensive evaluation of the functional and metabolic status of the myocardium in humans. Thirteen patients with congestive cardiomyopathy and eight healthy volunteers were imaged at 1.5 T with the one-dimensional chemical shift imaging technique for localization of P-31 MR spectroscopy and an electrocardiographically referenced gradient refocused sequence for imaging of the heart. Prominent peaks in the PDE and PME regions were observed in cardiomyopathic patients, but only the former peak was measured. The PCr/beta-ATP peak ratio was not significantly lower in cardiomyopathic patients compared with healthy subjects (1.51 +/- 0.08 vs 1.54 +/- 0.04). The ratios of PDE/PCr (0.80 +/- 0.07 vs 0.54 +/- 0.10) (P less than or equal to .01) and PDE/beta-ATP (1.19 +/- 0.10 vs 0.84 +/- 0.08) (P less than or equal to .05) were significantly higher in patients with dilated cardiomyopathy compared with healthy volunteers. Left ventricular systolic wall thickening was significantly lower and left ventricular peak and end-systolic wall stress and mass were significantly higher in cardiomyopathic patients compared with healthy volunteers. Thus, localized, gated P-31 MR spectroscopy combined with cine MR imaging allowed identification of both abnormal myocardial phosphate metabolism and abnormal ventricular function. While this study suggests that increased myocardial PDEs may be a marker for abnormal myocardium, the sensitivity and specificity of this marker need to be further evaluated.  相似文献   

12.
An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.  相似文献   

13.
OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A. KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448. Background: Various abnormalities in skeletal muscle have been demonstrated by biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high-energy metabolite composition at rest (HEMC) provides data on important metabolic characteristics; however, the significance of HEMC has not been clarified in patients with CHF. Therefore, we investigated HEMC in normal subjects and patients with CHF and examined its relation to muscle metabolic capacity and exercise tolerance. Methods: High-energy metabolites (phosphocreatine (PCr), inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P-magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP, and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size-matched normal subjects. Muscle metabolism was evaluated during local exercise of unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the rate of PCr breakdown in relation to the workload. Systemic exercise capacity was evaluated by a bicycle ergometer. Results: The ratio of PCr to ATP was significantly increased in patients with CHF compared with controls (3.06 +/- 0.43 vs 2.72 +/- 0.36, P < 0.05) and was significantly correlated with metabolic capacity (r = -0.37, P < 0.01) and with peak oxygen uptake (r = -0.45, P < 0.01). There was a significant correlation between metabolic capacity and peak oxygen uptake (r = 0.53, P < 0.001). Conclusion: HEMC was altered in patients with CHF, and this change was related to metabolic capacity and exercise capacity. These findings provide new insight into the mechanism of impaired muscle metabolism in CHF.  相似文献   

14.
To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.  相似文献   

15.
Human leg neuromuscular diseases: P-31 MR spectroscopy   总被引:1,自引:0,他引:1  
Phosphorus-31 magnetic resonance (MR) spectra of leg muscles in patients with the neuromuscular diseases Duchenne dystrophy, myotonic dystrophy, postpoliomyelitis, Werdnig-Hoffmann disease, and pedal dystonia were recorded. Ratios of beta-adenosine triphosphate (ATP), inorganic phosphate (Pi), alpha-glycerophosphorylcholine (GPC), and phosphomonoesters to phosphocreatine (PCr) were calculated from peak integrals and compared with normal muscle ratios. In all diseases studied, beta-ATP/PCr and Pi/PCr values showed an increase from normal values. The extent of increase in beta-ATP/PCr was related to the clinical severity of the disease, suggesting that this could be a useful noninvasive means of monitoring effectiveness of therapy for neuromuscular disorders. In myotonic dystrophy and Werdnig-Hoffmann disease, GPC/PCr values increased greatly. The intracellular pH in Duchenne and postpoliomyelitis muscles was slightly elevated compared with that in normal muscles. Hydrogen-1 MR images of muscles showed fat infiltration in all patients, more in weaker muscles and less in stronger muscles.  相似文献   

16.
The early effects of in vivo platinum-rhodamine (PtR) chemotherapy on tumor high-energy phosphorous metabolism was investigated using phosphorus-31 (31P) magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), and histologic examination in a subcutaneously implanted hamster melanoma model. PtR was chosen because of its potential antimitochondrial and antineoplastic properties. All melanomas were clearly observed on both T1- and T2-weighted images (T1WI and T2WI), with viable tumor regions generally characterized by low to intermediate intensity on T1WI and high intensity on T2WI. Necrotic regions were more variable in appearance, depending on the amount of cystic fluid and hemorrhage. No changes were detected on either T1WI or T2WI within 90 minutes of a tumoristatic dose of PtR (40 mg/kg) by visual examination, but slight differences were seen on calculations of relative signal intensities. However, this same dose of PtR caused a 50% drop in tumor ATP and phosphocreatine content (relative to Pi) measured by 31P MRS within 90 minutes of drug injection. Magnetic resonance spectroscopy appears to offer a sensitive means of detecting the earliest biochemical effects of chemotherapeutic agents that are known to affect tumor bioenergetics.  相似文献   

17.
To investigate the high-energy phosphate metabolic correlates of left ventricular (LV) dysfunction during the onset and recovery from severe, global myocardial ischemia in vivo, seven preinstrumented closed-chest dogs had ECG-gated phosphorus-31 (31P) NMR-spectroscopy (NMR-S) studies performed and LV micromanometer and sonomicrometer data measured before, during, and every 5 min following severe occlusive global myocardial ischemia. Ischemic LV + dP/dtmax fell from 2396 +/- 576 mm Hg/s at baseline to 2185 +/- 478 mm Hg/s (p less than 0.05) and did not normalize until after 30 min of reperfusion. LV ejection fraction (EF) decreased significantly (0.32 +/- 0.07 EF units to 0.12 +/- 0.13 EF units; p less than 0.05) and did not recover by 30 min of reperfusion (0.27 +/- 0.09 units; P less than 0.05 vs baseline). Simultaneous 31P NMR-S studies demonstrated excellent beta-ATP signal-to-noise (10 +/- 4:1). Myocardial acidosis occurred during global ischemia (delta pH = -0.22 +/- 0.23 units; p less than 0.05), with recovery at 30 min of reperfusion. Inorganic phosphate/phosphocreatine ratio (Pi/PCr) increased significantly during ischemia (0.46 +/- 0.07 to 0.61 +/- 0.07; P less than 0.05), with delayed normalization of this ratio at 30 min of reperfusion. beta-ATP peak area did not change during ischemia. Pi/PCr and LV contractility (+dP/dtmax) were significantly correlated at baseline (r = -0.70) and during global ischemia (r = -0.78; p less than 0.01), but not during recovery (r = 0.006; p = NS). Therefore, the simultaneous evaluation of high-fidelity hemodynamic data and topical 31P NMR-S can be performed in the intact state.  相似文献   

18.
PurposeTo study liver 31P MRS, histology, transient elastography, and liver function tests in patients with virus C hepatitis (HCV) or autoimmune hepatitis (AIH) to test the hypothesis that 31P MR metabolic profile of these diseases differ.Materials and methods25 patients with HCV (n = 12) or AIH (n = 13) underwent proton decoupled 31P MRS spectroscopy performed on a 3.0 T MR imager. Intensities of phosphomonoesters (PME) of phosphoethanolamine (PE) and phosphocholine (PC), phosphodiesters (PDE) of glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC), and γ, α and β resonances of adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide phosphate (NADPH) were determined. Liver stiffness was measured by transient elastography. Inflammation and fibrosis were staged according to METAVIR from biopsy samples. Activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALT) and thromboplastin time (TT) were determined from serum samples.ResultsPME had a stronger correlation with AST (z = 1.73, p = 0.04) and ALT (z = 1.77, p = 0.04) in HCV than in AIH patients. PME, PME/PDE, PE/GPE correlated positively and PDE negatively with inflammatory activity. PE, PC and PME correlated positively with liver function tests.Conclusion31P-MRS suggests a more serious liver damage in HCV than in AIH with similar histopathological findings. 31P-MRS is more sensitive in detecting inflammation than fibrosis in the liver.  相似文献   

19.
目的:运用3T高场强磁共振动态磷谱技术(^31P-MRS)在体评价骨骼肌线粒体能量代谢情况。方法:对20名正常人受试者骨骼肌进行动态31P-MRS采集,后期利用Matlab软件对无机磷(Pi)、磷酸肌酸(PCr)、三磷酸腺苷(ATP)等化合物的峰下面积进行定量分析,分别计算在静止期,运动末期及数个恢复期骨骼肌内高能磷酸化合物的含量,同时计算二磷酸腺苷(ADP)和细胞内PH值,评价磁共振动态磷谱技术对研究骨骼肌线粒体功能的价值。结果:肌肉运动时PCr含量明显降低,Pi、Pi/PCr和ADP升高,恢复期各含磷化合物含量逐渐恢复至静息水平。结论:3T高场强动态磷谱技术可以无创性定量评价骨骼肌线粒体功能,为肌肉的功能影像学提供客观证据,为以后客观研究肌肉相关疾病提供了理想的方法。  相似文献   

20.
31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, ATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.

Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.

Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.

In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.  相似文献   


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