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1.
骨性关节炎(OA)是在力学和生物学因素的共同作用下,软骨细胞、细胞外基质(ECM)及软骨下骨三者间分解和合成代谢失衡的结果。其病因及发病机制尚未明了,目前有多种学说解释OA的发生机制。一种观点认为,在某些炎症介质和细胞因子的作用下,基质金属蛋白酶的分泌异常增多,分解ECM,导致OA发生:另一种观点认为反复过量的负荷会损害软骨细胞和ECM,导致OA发生;还有一种观点认为,软骨细胞过度凋亡可能在OA的发病中产生了重要影响。  相似文献   

2.
骨关节炎(OA)的主要病理改变为关节软骨的损伤退变.碱性成纤维细胞生长因子(bFGF)是最有效的软骨细胞分裂素,bFGF缓释微球能维持其关节腔内的有效浓度.目前研究表明基质金属蛋白酶(MMP)-13、基质金属蛋白酶抑制剂(TIMP)-1为软骨细胞外基质合成和降解的主要调节因子.本研究旨在观察bFGF缓释微球治疗兔膝OA对MMP-13和TIMP-1 mRNA表达的影响,探讨bFGF治疗OA的作用机制.  相似文献   

3.
目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0....  相似文献   

4.
目的 探讨骨性关节炎各组织成分中细胞冈子、金属基质蛋白酶等炎性物质表达水平与疾病的关系.方法 获取行OA组关节置换及创伤性股骨颈骨折组患者手术时的软骨、滑膜组织和软骨下骨,苏木素-伊红(HE)染色行软骨下骨组织形态计量分析,应用放射免疫测定肿瘤坏死因子(TNF)-α与门细胞介素(IL)-1β,以酶联免疫吸附试验(ELISA)测金属基质蛋白酶(MMP)-9蛋白表达水平,并将两组结果进行t检验,软骨下骨组织计量值与细胞因子水平进行相关分析.结果 OA组较非OA对照组软骨下骨骨形成增加,骨质硬化骨小梁数目增加并错乱;滑膜组织中MMP-9表达是调;软骨组织中MMP-9及IL-1 β较对照组提高;而在软骨下骨,MMP-9、TNF-α及IL-β均有增高,并且与软骨下骨组织学改变相关联.结论 证实了OA促炎症条件的病理学基础,并且炎性改变与软骨硬化及关节软骨退变相关.  相似文献   

5.
目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0.01)。实验组MMP-9 mRNA与蛋白表达成正相关(r=0.924,P=0.000),TGF-β1 mRNA及蛋白表达亦成正相关(r=0.941,P=0.000);实验组MMP-9及TGF-β1蛋白表达成负相关(r=—0.762,P=0.000),MMP-9 mRNA及TGF-β1 mRNA表达成负相关(r=?0.681,P=0.000)。结论 OA中TGF-β1的高表达下调了关节软骨与滑膜中MMP-9的表达,对OA关节软骨起保护作用,从而延缓OA进展。  相似文献   

6.
目的探讨槲皮素对类风湿性关节炎成纤维样滑膜细胞(MH7A)炎症因子和基质金属蛋白酶的表达的影响及可能机制。方法选用人类风湿性关节炎成纤维样滑膜细胞(MH7A)为研究对象,TNF-α诱导MH7A细胞,用不同浓度的槲皮素干预,RT-PCR法检测对IL-1β、IL-6、IL-8、MMP-1、MMP-3、MMP-13的变化的影响,Western blot法检测对NF-κB的影响。结果槲皮素浓度依赖性地降低TNF-α诱导的MH7A细胞IL-1β、IL-6、IL-8、MMP-1、MMP-3、MMP-13的表达,对TNF-α诱导的MH7A细胞NF-κB的磷酸化有明显的抑制作用。结论槲皮素可有效地减轻类风湿性关节炎成纤维样滑膜细胞炎症因子及基质金属蛋白酶的表达,其机制可能和抑制NF-κB的表达相关,槲皮素是治疗类风湿性关节炎的潜在有效药物。  相似文献   

7.
目的 观察骨关节炎(OA)中基质金属蛋白酶(MMP)-1、3与白细胞介素-1β(IL-1β)的表达及关节软骨细胞凋亡,探讨其在OA发病机制中的作用.方法 将20只中国大白兔随机分成正常组(A组)、实验组(B组),每组10只,A组未造模,B组采用Hulth法制成OA模型,4周后取胫骨平台关节软骨进行组织病理学检查,采用免疫组织化学和原位末端标记细胞凋亡检测法分别检测关节软骨和滑膜中的MMP-1、3、IL-1β及软骨细胞凋亡指数(AI)的水平.结果 组织病理学检查可见,B组关节软骨退变程度明显重于A组,符合OA关节软骨退变特征;通过检测MMP-1、3,IL-1β和AI,A组的结果分别是21.005±9.406、18.697±8.225、0.100±0.040和14.900±3.400,B组的结果分别是56.147±22.340、46.182±20.561、0.180±0.060和25.400 ±5.200;B组MMP-1、3和AI的水平均明显高于A组(P<0.01),B组IL-1β水平高于A组(P<0.05).结论 MMP-1、MMP-3、IL-1β的表达及关节软骨细胞凋亡在OA发病机制中作用重要,其异常升高与OA关节软骨退变和炎症反应密切相关.  相似文献   

8.
目的研究柚皮苷在炎症环境下对人骨关节炎(OA)软骨细胞凋亡的影响和可能的作用机制。方法采用不同浓度(0、0.1、1、10、100 mg/L)柚皮苷对 OA 软骨细胞进行预处理2 h 后,加入或不加入炎症因子混合液(白细胞介素-1β5 ng/ml 和肿瘤坏死因子-α20 ng/ml)共作用24 h。首先检测柚皮苷对炎症环境下软骨细胞活性和凋亡的影响,然后检测软骨细胞在柚皮苷作用下的一氧化氮(NO)水平及半胱氨酸天冬氨酸特异性蛋白酶(caspase)-3、caspase-8活性变化情况。结果柚皮苷预处理后软骨细胞在炎症因子刺激下发生凋亡显著减轻,且其抑制细胞凋亡作用具有浓度依赖性。进一步分子生物学检测显示,柚皮苷对 NO 生成及激活的 caspase 信号转导通路具有明显抑制作用。结论柚皮苷能有效抑制人 OA 软骨细胞凋亡,其作用机制可能是柚皮苷阻断了 NO 产生并抑制了下游的 caspase 信号通路,有望应用于 OA 治疗新药的研发。  相似文献   

9.
目的通过检测与创面愈合进程相关的组织基因表达,探讨采用负压创面治疗(nagetive pressure wound therapy,NPWT),促进糖尿病足溃疡(diabetic foot ulcer, DFU)愈合的作用机制。方法将纳入的50例DFU患者随机分成NPWT组(25例)和对照组(25例)。对照组接受局部湿敷治疗。两组患者治疗前后10 d均取创面肉芽行组织活检,利用RT-PCR检测转移生长因子-β1(transforminggrowth factor beta 1, TGF-β1)、血管内皮生长因子(vascular endothelial growth factor, VEGF)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-1β(interleukin-1β, IL-1β)、基质金属蛋白酶-1(matrix metalloproteinase-1, MMP-1)、基质金属蛋白酶-9(matrixmetalloproteinase-9, MMP-9)和基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1, TIMP-1)的mRNA表达,并进行对比分析。结果治疗后10 d,NPWT组患者创面肉芽组织中VEGF、TGF-β1和TIMP-1 mRNA的表达较治疗前显著增加,IL-1β、TNF-α、MMP-1和MMP-9 mRNA的表达显著下降(P<0.05);而对照组上述各项指标的mRNA表达,治疗前后均无显著变化(P>0.05)。结论 NPWT可能通过影响生长因子、炎症细胞因子和基质金属蛋白酶的表达来促进DFU愈合。  相似文献   

10.
Smad与肾纤维化   总被引:11,自引:1,他引:10  
转化生长因子-β(transforming growth factor-β,TGF-β)是介导肾小球硬化和肾间质纤维化关键的细胞因子,其作用包括趋化和活化炎性细胞,介导肾小管上皮细胞向间充质细胞转分化,以及刺激细胞外基质蛋白的合成及降低基质金属蛋白酶的活性和俄增加蛋白酶抑制剂的合成来促进细胞外基质的沉积。由于TGF-β在肾纤维化中的核心作用,TGF-β信号传导机制引起了人们极大的兴趣。  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.  相似文献   

13.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

14.
Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg−1 followed by 0.15 mg · kg−1 · h−1, n=8) or verapamil (0.1 mg · kg−1 followed by 0.3 mg · kg−1 · h−1, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.  相似文献   

15.
Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.  相似文献   

16.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

17.
Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.  相似文献   

18.
Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.  相似文献   

19.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

20.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

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