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1.
By titration of two different stannous kits for 99mTc labeling of red blood cells (RBC) we found concentrations of 1-2 micrograms tin per ml of blood to give the highest labeling yield. Using a new kit containing 2 micrograms of tin and 0.1% hypochlorite (NaOCl) as an oxidizing agent we labeled RBC with 99mTc avoiding centrifugation of cells. To evaluate this new procedure we assessed the dependency of tin incubation time, and addition of 4.4% EDTA as a chelating agent on labeling efficiency. We also measured the dependency of EDTA on the stability of the label. Optimal conditions for labeling of 1 ml of whole blood using the new stannous kit were: 5-10 min of tin incubation, 0.2 ml of 0.1% hypochlorite, and 15 min of 99mTc incubation. This procedure resulted in a labeling efficiency of at least 96%. The overall effect of EDTA was not an increased labeling efficiency, and EDTA increased the stability of the label with only a few percent. The promising results of this new labeling approach encourage to further laboratory investigations and eventual clinical evaluation of the procedure.  相似文献   

2.
This study analyzes the transport characteristics of the pertechnetate anion across membranes of human erythrocytes during labeling with technetium-99m (99mTc). Transport of this anion is inhibited after incubation at low temperature, indicating the involvement of a process with high activation energy. Transport is also decreased by two well-known inhibitors of the band-3 anion transport system and is not affected by inhibition of the Na/K/Cl co-transport system. From these results we conclude that, in the process of labeling red blood cells with 99mTc, the pertechnetate anion may reach the interior of the erythrocyte through the band-3 anion transport system.  相似文献   

3.
Twenty-three mature Sprague-Dawley male and female rats were simultaneously injected with trace quantities of [153Gd]DTPA and [99mTc]DTPA and 0.5 mmol/kg of nonradioactive gadolinium DTPA. Rats were killed at 1 min, 5 min, 10 min, 15 min, and 30 min after the intracardiac bolus injection. The heart, lungs, liver, brain, kidney, and blood were excised and counted in a well-counter to determine the amount of the injected material in each organ and blood. In order for the percent of total injected activity to be determined, a technique was developed which allowed discrimination of the 140 keV gamma-ray of 99mTc from sum peaks of 153Gd when the latter is counted in a well-counter with 4 pi geometry. Although the distribution of the two DTPA compounds was qualitatively similar, statistical analysis indicated that the amount of 99mTc deposited in the lungs was higher than 153Gd (p = 0.03), the amount of 99mTc deposited in the kidneys was lower than 153Gd (p = 0.0004) and the amount of 99mTc in the blood was higher than 153Gd (p = 0.0022). This may be due to the greater binding of [99mTc]DTPA or its minor impurities to plasma proteins.  相似文献   

4.
BACKGROUND: Routine technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) radiochemical purity measurements have revealed occasional unacceptably low values. Preliminary investigations suggested a causal link with the residence time of sodium chloride injection in the syringe used to reconstitute the MAG3 kit. OBJECTIVES: To investigate the cause of this phenomenon, determine how it can be avoided and establish whether it occurs with other 99mTc radiopharmaceuticals. METHODS: 99mTc-MAG3 was prepared by drawing sodium chloride injection into a lubricated, three-part, 10 ml Plastipak syringe and using it to reconstitute a MAG3 kit immediately or after a 15 min incubation period. The radiochemical purity was measured by high-performance liquid chromatography. The experiment was repeated using lubricant-free, two-part, Norm-Ject syringes and lubricated, two-part, Monoject syringes (15 min incubation only). To investigate the influence of Plastipak's rubber components on the radiochemical purity, samples were prepared using sodium chloride injection that had been incubated with lubricated or lubricant-free rubber plunger ends. Similar experiments were performed to determine the effect of Plastipak on 99mTc-exametazime, 99mTc-sestamibi and 99mTc-tetrofosmin. RESULTS: The radiochemical purities of 99mTc-MAG3 prepared with sodium chloride injection incubated for 0 and 15 min in Plastipak syringes were 96.4+/-0.5% and 89.4+/-5.5%, respectively. The difference was significant (P<0.05, n=10). With Norm-Ject syringes, the radiochemical purities were 96.5+/-0.5% and 96.6+/-0.5%, respectively. The difference was not significant (P>0.05, n=10). With Monoject syringes, the radiochemical purity was 96.6+/-0.4% (n=10). 99mTc-MAG3 prepared using sodium chloride injection treated with lubricated and unlubricated syringe rubber plunger ends had radiochemical purities of 85.3+/-6.6% and 82.1+/-6.5% (n=5), respectively. The radiochemical purities of other 99mTc radiopharmaceuticals prepared using sodium chloride injection incubated for 0 or 15 min in Plastipak syringes were as follows: 99mTc-exametazime, 95.3+/-0.6% and 94.5+/-1.8%; 99mTc-sestamibi, 98.0+/-0.6% and 97.7+/-0.6%; 99mTc-tetrofosmin, 96.5+/-0.2% and 97.0+/-0.4%. None of the differences was significant (P>0.05, n=5). CONCLUSIONS: A lipophilic impurity, originating from the rubber plunger of a three-part Plastipak syringe, is formed in 99mTc-MAG3 when the sodium chloride injection used to reconstitute the kit is in the syringe for a prolonged time. The effect is eliminated by using a two-part syringe or by injecting the sodium chloride injection into the kit immediately. The phenomenon does not occur with 99mTc-exametazime, 99mTc-sestamibi or 99mTc-tetrofosmin.  相似文献   

5.
Cellular uptake characteristics of hexakis(methoxyisobutylisonitrile)technetium(I) ([99mTc]MIBI), a myocardial perfusion imaging agent, were evaluated in cultured chick embryo heart cells. Myocyte net uptake of 99mTc-MIBI approached a plateau with a half-time of 9.3 +/- 1.5 min (mean +/- s.e.m.; n = 10). Tracer [99mTc]MIBI showed apparent competitive displacement by carrier [99Tc]MIBI at relatively high molar ratios ([99mTc]MIBI/[99Tc]MIBI) indicating a low affinity cellular retention process (apparent KD approximately 7 x 10(-5)). Metabolic inhibition induced by pre-incubation of cells for 2.5 hr in rotenone (10 microM), iodoacetate (1 mM), or both metabolic inhibitors together reduced 1-min [99mTc] MIBI uptake to 74.1% +/- 8.0% (p less than 0.05), 6.2% +/- 3.4% (p less than 0.01), and 10.1% +/- 3.6% of control (p less than 0.01), respectively (n = 11-12). Half-maximal inhibitory concentration of iodoacetate was approximately 5 microM. Iodoacetate inhibition of [99mTc]MIBI uptake kinetics was time-dependent; no significant effect on [99mTc]MIBI uptake was seen during the first 60 min of metabolic inhibition despite significant depletion of ATP content determined on the same preparations (control ATP: 40.2 nmoles/mg protein versus iodoacetate incubation: 2.8 nmoles/mg protein; p less than 0.01). However, prolonged metabolic blockade did eventually depress 1-min [99mTc]MIBI uptake. These data indicate that a late component of myocardial cell injury can depress [99mTc]MIBI cellular uptake.  相似文献   

6.
Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.  相似文献   

7.
Technetium-99m direct radiolabeling of lanreotide: a somatostatin analog.   总被引:6,自引:0,他引:6  
Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide 99mTc. Labeling was accomplished by reduction of the cysteine bridge, which provided sulfhydryl groups for chelation with 99mTc. Stannous chloride was used as reducing agent, while tartrate acted as transchelating agent. Lanreotide (100 microg), stannous chloride dihydrate (100 microg) and tartaric acid (64 microg) were dissolved in acetate/acetic acid buffer (pH 2.8). After overnight (approximately 18 h) incubation, approximately 444 MBq (12 mCi) 99mTc was added and kept in boiling water for 30 min. More than 97% labeling efficiency was confirmed by RP-HPLC, ITLC-SG and C18 cartridge analysis. Radiolabeling results in one major peak when analyzed by reverse-phase HPLC. The stability of the 99mTc-peptide bond was evaluated by cysteine challenge studies.  相似文献   

8.
The effect of increasing intensities of exercise on the water space and the red blood cell volume of the dog gracilis muscle was determined with 125I-labelled iodoantipyrine (n = 8) and 99mTc labelled red blood cells (n = 4). A sodium iodide scintillation probe attached to a two channel multiscaler and printer recorded the 125I activity of the muscle as a measure of the water space and the 99mTc activity as a measure of the red cell space. An electro-magnetic flow probe recorded muscle blood flow: aortic pressure was measured with a catheter in the mid-abdominal aorta. At least 30 min after i.v. administration of iodoantipyrine and red blood cells, the obturator nerve was electrically stimulated to produce muscle contraction at 1 contraction per second for 5 min. Data were recorded prior to exercise, during the 5 min exercise period, and for 10 min after exercise. During the greatest exercise period there was an eightfold increase in muscle blood flow, but only a small increase in [125I]iodoantipyrine activity (2.7 +/- 0.8%, 95% confidence limits) and 99mTc red blood cell activity (3.2 +/- 2.1%). Both values promptly returned to baseline during recovery. These data show that there is a minimal change in the water space and blood volume of the exercising dog gracilis muscle.  相似文献   

9.
(99mTc)HMPAO is a radiopharmaceutical used for SPECT imaging of regional cerebral perfusion and for labeling cellular blood elements. The addition of methylene blue enhanced the stability of lipophilic (99mTc)HMPAO complex up to 3 h after reconstitution, 86.9+/-4.2% compared to 49.8+/-8.9% for the non-stabilised complex and persists over time (86.2+/-3.5% after 15 min compared to 78.2+/-4.0% after 3 h). The method widely used for estimation of radiochemical purity is a standard chromatographic procedure which is quite time-consuming taking about 30 min. Comparison of the more rapid and simple solvent extraction method with octanol, which needs only about 10 min to complete. showed a good correlation with the chromatographic method (84.4+/-4.4% compared to 89.1+/-4.3%). Using ethyl acetate as solvent instead of octanol gave a slightly higher extraction rate of the lipophilic complex (91.5+/-5.5% compared to 89.1+/-4.3%). Further, the ethyl acetate extraction method results in an overestimation, extracting partly secondary complex. It is confirmed, that the stability of the lipophilic (99mTc)HMPAO complex can be increased with methylene blue. The octanol extraction method, using higher extraction volume (up to 3 ml), is recommended as a fast and efficient approach for the quality control in daily clinical routine.  相似文献   

10.
A technique for labeling leukocytes with 99mTc using hexamethylpropylene-amineoxime (HMPAO) was evaluated in vitro. The labeling procedure resulted in a cell bound fraction of radioactivity of 56% after 99mTc incubation and 96% after 1 washing of cells. In the final cell suspension 84% of the radioactivity was attached to the polymorphonuclear (PMN) leukocytes constituting 94% of white cells. Only 5% was bound to residual red blood cells. The stability evaluated in autologous plasma showed a decline of cell bound activity from 96% to 84% over 3 h. The chemotactic function of PMN leukocytes was unaffected by the labeling procedure. These findings demonstrate that HMPAO, albeit cell unspecific, is efficient for labeling PMN leukocytes with 99mTc. The stability of the labeling procedure is high and the technique does not affect cell function. No other current 99mTc leukocyte labeling technique possesses all these qualities.  相似文献   

11.
Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo.  相似文献   

12.
The biodistribution patterns of 99mTc (99mTc-lymph) and 111In-lymphocytes with [111In-(Sn)-lymph] or without (111In-lymph) stannous ion treatment was compared in Lewis rats. Syngeneic lymphocytes were labeled with either 125 microCi (4.63 MBq) 99mTc or 5 microCi (185 kBq) 111In per 2 x 10(7) cells. Mean labeling efficiency for 99mTc and 111In was 68.61% +/- 3.90% (SEM) and 87.22% +/- 2.01% (SEM) respectively. 99mTc-lymph (n = 4), 111In-lymph (n = 6) and 111In-(Sn)-lymph (n = 6) rats received 2 x 10(7) cells and were killed 18 h later. While 99mTc-lymph demonstrated significantly less localization in spleen, lymph nodes, and blood (P(F) less than 0.01) as compared with 111In-lymph, 111In-(Sn)lymph also demonstrated a significant difference (P[F]= 0.0001) in lymph node accumulation when compared to 111In-lymph. As the activity levels utilized are not associated with cell radiation damage, these alterations in biodistribution do not reflect viability or chromosomal damage, but appear related to stannous ion exposure.  相似文献   

13.
The lipophilic 99mTc-HMPAO complex can be used for labelling platelets as well as granulocytes. Platelets were isolated according to standard isolation procedures for the evaluation of the optimal labelling parameters. The labelling efficiency (%) depends on incubation temperature (22 degrees C: 40%: 37 degrees C: 50%), incubation time (3 min: 20%, 25 min: 55%) and the incubation medium (plasma: 40%; saline 50%). The 60 min 99mTc elution out of the platelets ranged around 8%. The platelet recovery used as a quality control parameter is around 25% +/- 4% and is stable for at least 240 min. The high elution rate out of the platelets leads to renal excretion of the label and hence to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can normally be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection. In conclusion, 99mTc-HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet survival studies, because of the short physical half life of 99mTc.  相似文献   

14.
The mechanisms by which [99mTc]pertechnetate becomes attached to stannous-primed red blood cells are not known in detail. To study the problem further, the effect of red cell surface charge on labeling efficiency was evaluated. Red cell surface charge was reduced by using the enzyme neuraminidase to remove the terminal charge-bearing sialic acid moiety of the membrane glycoprotein. Forty-five blood samples from six volunteers were treated with neuraminidase for varying lengths of time, resulting in the removal of from 11% to 99% of the normal negative surface charge, as determined from electrophoretic mobility measurements. There was excellent linear correlation between labeling efficiency and the remaining red cell surface charge for values down to 20% of normal (r = 0.89). When surface charge was less than 20% of normal, labeling efficiency was constant at 30%. Eleven blood samples from three donors were divided into two groups that were treated with neuraminidase either before or after they were labeled. The labeling efficiency was independent of the order in which the steps were performed. No evidence for shifting of the radiolabel from the cell membrane to hemoglobin was found. The results suggest that clinical conditions associated with a reduction of sialic acid on the erythrocyte membrane may be one cause of decreased red blood cell labeling efficiency, and that increased membrane permeability for reduced technetium species may be responsible for the decrease.  相似文献   

15.
Currently, there is no low-molecular-weight agent for imaging of the pulmonary circulation. Adrenomedullin (AM) is a peptide predominantly cleared by the pulmonary circulation through specific endothelial receptors. We developed human AM derivatives radiolabeled with 99mTc and evaluated their biodistribution, plasma kinetics, and utility as pulmonary vascular imaging agents. METHODS: Two derivatives radiolabeled with 99mTc were evaluated: the natural cyclic form of the peptide, to which the chelator diethylenetriaminepentaacetic acid was added (C-DTPA-AM), and the linear form, which allows direct labeling (L-AM). The compounds were injected into dogs, and the activities of the tracers in blood and in organs were determined with a nuclear medicine camera. Single-pass pulmonary clearance was measured by the indicator dilution technique. The capacity to image perfusion defects was evaluated after surgical pulmonary artery ligation. RESULTS: Both derivatives were rapidly cleared from plasma, with elimination half-lives of 42 and 32 min for C-DTPA-AM and L-AM, respectively. The lungs retained most of the activity after 30 min; this activity was higher (P = 0.02) for L-AM (42% +/- 5% [mean +/- SEM]) than for C-DTPA-AM (27% +/- 1%). Lung activity slowly declined over time but was maintained after 2 h at approximately 20% for both tracers. The single-pass pulmonary clearance of plasma L-AM was 414 +/- 85 mL/min. There was a higher level of urinary excretion of L-AM than of C-DTPA-AM. After pulmonary artery ligation, perfusion defects were easily detectable by external imaging. CONCLUSION: AM derivatives are promising compounds for molecular imaging of the pulmonary circulation. L-AM displayed higher levels of initial lung retention and of kidney excretion.  相似文献   

16.
To investigate the usefulness of the 20 min 99mTc-pertechnetate uptake test, the records of 246 consecutive patients were reviewed. Of these, 192 patients (151 females, 41 males; 10 weeks to 78 years) had at least one year clinical follow-up or a confirmed diagnosis by biopsy or surgery and were included in our study. In these patients, the 99mTc pertechnetate uptake and hormonal values (T3 resin uptake, T4 RIA, T-index) were obtained. These results were then compared to the clinical diagnosis at the time of the uptake and one year later. All patients received an i.v. injection of 5 mCi of 99mTc pertechnetate. Imaging was performed using a pinhole collimator and a scintillation camera interfaced to a computer. Regions of interest for the thyroid and the background were used to calculate the 20 min 99mTc pertechnetate uptake as a percentage of the injected dose. 99mTc uptake and hormonal values were confirmatory in 158 patients (82.3%): 138 were euthyroid, 18 were hyperthyroid and 2 were hypothyroid. In 29 other patients (15.1%) the pertechnetate uptake provided useful additional information and helped to identify Hashimoto's thyroiditis (8 patients); thyroid suppression by exogenous iodide, steroids or T4 (7 patients); overtreated hyperthyroidism (1 patient); persistent hyperthyroidism (5 patients); different stages of Grave's disease (4 patients); and toxic nodular goiter (4 patients). The 99mTc uptake was misleading in 5 euthyroid patients (2.6%). We have found the 99mTc pertechnetate uptake a useful adjunct to measurement of hormonal levels in patients with suspected thyroid disease.  相似文献   

17.
Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.  相似文献   

18.
This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.  相似文献   

19.
Technetium-99m t-butylisonitrile ([99mTc]TBI) is a promising new radiotracer for myocardial imaging. Its myocardial uptake is sufficiently high in humans to permit planar, tomographic, and gated images of excellent technical quality. We studied the behavior of [99mTc]TBI in the dog at rest and under conditions of hyperemia and reperfusion in order to determine the relationship between [99mTc]TBI myocardial concentration and blood flow. After permanent occlusion of the left anterior descending artery, the correlation between the relative myocardial concentration of [99mTc]TBI and regional myocardial blood flow (RMBF) measured with radiolabeled microspheres was excellent. In a dog model of transient hyperemia, the concentration of [99mTc]TBI was directly related to blood flow but underestimated the degree of hyperemia. Technetium-99m TBI redistributed into transiently ischemic myocardium. The myocardial concentrations of [99mTc]TBI and thallium-201(201TI) in transiently ischemic myocardium were similar at 10 and 30 min following reperfusion and were significantly higher than blood flow prior to reperfusion. When [99mTc]TBI was injected into the left anterior descending artery, the washout was slow, falling to 78% of initial activity at 120 min after injection. In conclusion, [99mTc]TBI reflects regional myocardial blood flow accurately in ischemic and normal resting myocardium and underestimates blood flow at high flows. The rate of myocardial redistribution after reperfusion is similar for [99mTc]TBI and 201TI.  相似文献   

20.
Results are reported on the use of a commercial kit for the labeling of human serum albumin with 99mTc. One-hour blood levels obtained in 20 subjects undergoing gated cardiac imaging were found to be 46.0 +/- 10.5% (s.d.) of the administered dose. The highest labeling efficiencies (94.2 +/- 9.3%) were obtained when human serum albumin 25% (salt-poor) was used. Satisfactory nuclear cardiac ventriculographic images were obtained in patients receiving the radiopharmaceutical when the labeling efficiency was at least 85%. Occasional batches were milky in appearance, contained black particulate matter, were acidic, or contained a high percentage of unbound 99mTc activity. Although this kit makes 99mTc-human serum albumin accessible to most nuclear medicine facilities for general clinical use, an active quality control program is required prior to use in patients.  相似文献   

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