Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

NSAIDs抗RSV作用机制的网络药理学分析

目的:通过网络药理学方法探寻非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)作为抗炎止痛药对呼吸道合胞病毒(RSV)的潜在作用机制,通过网络药理学研究筛选抗RSV的最有影响力的NSAIDs药物。方法:将美国食品和药物管理局(FDA)批准的NSAIDs(19种活性药物和一种前药)用于本研究。通过Swiss Target Prediction和PubChem数据库收集NSAIDs的靶点,在GeneCards数据库中检索疾病RSV靶标。利用韦恩网绘制NSAIDs靶点蛋白与RSV靶点蛋白的交集,在STRING数据库对药物-疾病交集靶蛋白进行蛋白互作分析,在Cytoscape 3.9.0中对该网络进行美化。在DAVID数据库中对交集靶蛋白进行京都基因和基因组百科全书(KEGG)通路富集分析,利用微生信在线绘图工具绘制KEGG通路富集分析的气泡图,通过Cytoscape 3.9.0进行通路-靶点-成分网络分析,最后通过分子对接(AutoDock Vina)确定NSAIDs对靶蛋白的结合亲和力。结果:共搜集到421个NSAIDs靶点,391个与RSV相关的靶点,39个重叠的靶蛋白,基因组富集分析显示了37条抗RSV的信号通路,探索出MAPK1、AKT1和MAP2K1是与B细胞受体信号通路相关性最大的靶蛋白。结论:三种NSAIDs(舒林酸、罗非昔布、双氯芬酸)可能通过使MAPK1、AKT1和MAP2K1等相关靶蛋白失活来阻断B细胞受体信号通路,从而缓解RSV引起的支气管炎和肺炎。

Split-dose or hybrid nonsteroidal anti-inflammatory drugs and Nacetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis

BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.

Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug

AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors on the ulceration in small intestines of rats.METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin)did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others(pravastatin, atorvastatin).CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.

NSAIDs在幽门螺杆菌相关性胃黏膜病变中的作用

目的了解NSAIDs与Hellicobecterpylori感染在胃黏膜病变中的作用。方法患者190例,①病例选择:连续服用NSAIDs治疗2周～12周190例。男性121例,女性69例。平均年龄55岁。②均经胃镜检查和病理组织学检查。对糜烂性胃炎的胃镜诊断和病理诊断胃黏膜炎症分级。③进行H.pylori感染的检测。分为H.pylori感染组与H.pylori阴性组。分析两组的病理组织学改变的特点,了解是否有显著性差异。结果①胃镜检查,轻度糜烂106例(55.8%,106/190)。中重度糜烂84例(44.2%,84/190)。糜烂性胃炎的轻重程度与服药的剂量时间无明显的相关性。②H.pylori感染组46例(24.2%)。H.pylori阴性组144例(75.8%)。③两组病人胃镜诊断的糜烂性胃炎程度无显著性差异(P>0.05)。④病理情况:H.pylori感染组黏膜中重度胃炎明显多于H.pylori阴性组(P<0.01)。⑤病理改变中有淋巴组织增生56例。其中H.pylori感染组有淋巴组织增生22例(47.8%),H.pylori阴性组34例(23.6%)。134例未见淋巴组织增生,其中H.pylori感染组24例(52.2%),H.pylori阴性组110例(76.4%)。两组相比,有显著性差异(P<0.01)。结论服用NSAIDs2周以上对胃黏膜有不同程度的损伤。服用NSAIDs同时合并H.pylori感染的患者的胃黏膜损伤的严重程度远远高于非感染组。NSAIDs与H.pylori感染是导致胃黏膜损伤的独立危险因子,它们对胃黏膜的损伤作用是叠加的。NSAIDs相关性胃病合并H.pylori感染,根除H.pylori治疗是必要的。

433例非甾体抗炎药物不良反应报告分析

目的通过对非甾体抗炎药物(NSAIDs)致药品不良反应(ADRs)进行分析,了解NSAIDs致ADRs发生特点,为临床合理安全用药作参考。方法收集2022年10月1日至2023年9月30日,国家药品不良反应监测系统接收的济南市范围内的所有NSAIDs相关ADRs报告,共计535例;剔除药品等相关信息不详报告,最终433例纳入统计分析,对报告一般情况、性别和年龄、NSAIDs类别、ADR发生时间、给药途径以及ADRs累及系统/器官和临床表现等进行统计分析。结果NSAIDs所致ADRs患者中,一般报告379例;严重ADR报告54例,转归情况大部分为痊愈或好转;男女性别比为1∶1.23,多发生于≥60岁人群(66.7%);NSAIDs涉及乙酸类(24.2%)、丙酸类(22.2%)、甲酸类(21.5%)等十大类别:ADRs发生时间≤1天(264例,61.0%);给药途径以口服(256例,59.1%)和静脉(133例,30.7%)为主。433例ADRs报告中累及多个系统/器官,共计551例次,其中排名前3位分别为胃肠系统(310,56.3%)、皮肤及其附件(122,22.1%)和视觉障碍(25,8.7%);54例严重报告累及多个系统/器官共计76例次,主要累及皮肤及其附件系统(40,52.6%)、胃肠系统(14,18.4%)和泌尿系统(4,5.3%),临床表现主要以皮疹、瘙痒、呕吐等为主。结论NSAIDs在临床上使用广泛,会导致不同程度ADRs,临床中应合理用药,确保用药安全。

药物治疗干眼的临床应用及研究进展

干眼又称作干燥性角结膜炎,其临床表现为眼部干涩,有搔痒感、灼烧感、视物模糊等症状,严重影响患者的生活质量。近年来干眼的发病率逐年升高,已成为眼科临床的常见疾病之一。目前治疗干眼的手段主要有药物治疗、手术治疗和临床护理等,其中药物治疗是治疗干眼最为常用的手段。本文对近年来临床上基于渗透通路和炎症通路的药物治疗干眼的应用及研究进展进行归纳总结,为后续干眼的治疗及药物研发提供一些思路。

Synthesis and Characterization of Naproxen-Salicylate Derivatives as Potential Dual-Targeted Inhibitors of Dihydrofolate Reductase

Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). Chemotherapy drugs such as methotrexate help to slow the progression of cancer by limiting the ability of dividing cells to make nucleotides by competitively inhibiting DHFR. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been previously reported to exhibit competitive inhibition of DHFR, in addition to their primary action on cyclooxygenase enzymes. This interaction interferes with the enzymatic reduction of dihydrofolate to tetrahydrofolate, thereby impeding the folate metabolism pathway essential for nucleotide synthesis and cell proliferation. This activity stems from their structural resemblance to the p-aminobenzoyl-l-glutamate (pABG) moiety of folate, a substrate of DHFR. It has been established that NSAIDs containing a salicylate group (which has structural similarities to pABG), such as diflunisal, exhibit stronger DHFR-binding activity. In this study, we synthesized salicylate derivatives of naproxen with the aim of exploring their potential as inhibitors of DHFR. The interactions between these derivatives and human DHFR were characterized using a combination of biochemical, biophysical, and structural methods. Through polyacrylamide gel electrophoresis (PAGE) analysis, enzymatic assays, and quantitative ELISA, we investigated the binding affinity and inhibitory potency of the synthesized salicylate derivatives towards DHFR. The findings of this study suggest the potential of salicylate derivatives of naproxen as promising candidates for the inhibition of DHFR, thereby offering novel therapeutic opportunities for modulating the inflammatory process through multiple pathways. Further optimization of these derivatives could lead to the development of more efficacious dual-targeted analogs with enhanced therapeutic benefits.

Triggers of histologically suspected drug-induced colitis

BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.

Efficacy of Nonsteroidal Anti-inflammatory Drugs for Treatment of Uncomplicated Lower Urinary Tract Infections in Women:A Meta-analysis

Urinary tract infections(UTIs)are among the most frequent causes for antibiotic prescription and;therefore,alternative treatment options for UTIs can potentially reduce antibiotic usage and development of resistance.To evaluate the efficacy of nonsteroidal antiinflammatory drugs(NSAIDS)for the treatment of uncomplicated lower UTIs in women,this study implemented a meta-analytic approach to evaluate the results of available randomized clinical studies from online databases.A total of four trials involving 1144 patients with uncomplicated lower UTIs were included in the final evaluation.Results showed that symptom resolution at Day 3-4 in the NSAIDs group was significantly lower than that in the antibiotics group[pooled odds ratio(OR)=0.41,95%confidence interval(CI):0.23-0.74,P<0.05].However,there was no significant difference between the NSAIDs and antibiotics groups in symptom resolution at Day 7(pooled OR=0.43,95%CI:0.17-1.06,P=0.07),secondary antibiotic treatment rate at Day 28-30(pooled OR=1.15,95%CI:0.16-7.98,P=0.89)and adverse events rate(pooled OR=1.09,95%CI:0.61-1.96,P=0.77).Therefore,this metaanalysis suggests that,although inferior to antibiotics in fast symptom resolution,symptomatic treatment with NSAIDs can be considered as an alternative treatment option for uncomplicated lower UTIs in women.However,given the low number of randomized controlled trials that met inclusion criteria in this meta-analysis,efficacy of NSAIDs for treatment of uncomplicated lower UTIs should be further evaluated in more comprehensive clinical studies.

基于“动静结合,以动为主”的清宫正骨拔戳揉捻法治疗肱骨外上髁炎临床观察

目的观察基于“动静结合,以动为主”理论的清宫正骨拔戳揉捻法治疗肱骨外上髁炎(LE)的临床疗效。方法选取2020年10月—2021年12月中国中医科学院望京医院就诊的LE患者64例,随机分为手法组和对照组各32例。2组均予宣教和肘部练功法指导,手法组采用清宫正骨拔戳揉捻法治疗,3次/周,治疗4周;对照组采用双氯芬酸二乙胺乳胶剂外用并佩戴护肘制动,1次/d,治疗4周。对比2组在治疗前、治疗结束后即刻以及治疗完成后2个月的视觉模拟评分(VAS)、美国特种外科医院(HSS)评分以及肘部压痛阈值。结果与治疗前比较,2组治疗结束后即刻和完成后2个月的VAS评分、HSS评分、肘部压痛阈值均改善(P<0.05);与对照组比较,手法组治疗结束后即刻和完成后2个月的VAS评分、HSS评分及压痛阈值改善明显(P<0.05)。与治疗结束后即刻比较,手法组治疗完成后2个月的VAS评分差异无统计学意义(P>0.05),HSS评分及压痛阈值下降(P<0.05);对照组治疗完成后2个月的VAS评分升高,HSS评分及压痛阈值下降(P<0.05)。结论与外用非甾体抗炎药治疗比较,基于“动静结合,以动为主”理论的清宫正骨拔戳揉捻法可显著减轻LE患者肘关节疼痛,改善关节活动功能,治疗结束长时间后仍有较好的止痛效果。

非甾体抗炎新药联苯乙酸的合成

以苯乙腈为起始原料，经四步反应合成非甾体抗炎新药联苯乙酸．通过对各步反应进行研究，找到了理想反应条件，四步反应总收率２７ ．６ ％ ．

阿司匹林预防结直肠腺瘤的Meta分析

目的系统性评价阿司匹林预防结直肠腺瘤的有效性和安全性。方法结合所有随机双盲安慰剂数据对照试验来评价阿司匹林对结直肠腺瘤的预防作用,检索Medline(1966年1月至2009年1月)数据库,OVID(1996年1月至2009年1月)数据库,Embase(1980年1月至2009年1月)数据库,中国生物医学文献数据库(CBMdisk,1996年1月至2009年1月),并鉴定随机对照研究(RCT)的质量。按Jadad质量评分进行评定。用Rev Man 4.2软件进行荟萃分析。结果共有5篇文献,其中4篇为随机临床对照试验,1篇为队列研究;共有24 770例纳入研究,任何剂量阿司匹林与安慰剂比较,预防结直肠腺瘤的发生,P=0.002,PetoOR=0.82,95%CI=0.72～0.93;高剂量阿司匹林和安慰组比较,P=0.006,PetoOR=0.78,95%CI=0.65～0.93;小剂量阿司匹林和安慰组比较P=0.05,PetoOR=0.85,95%CI=0.72～1.00;各剂量阿司匹林组均可预防结直肠腺瘤的发生;发生不良反应事件的危险度各剂量阿司匹林组间比较差异无统计学意义,但中风的发生率高于安慰剂组。结论阿司匹林剂可以有效消退结直肠腺瘤性息肉,但其潜在的风险,尚不可作为常规用药,还需临床研究进一步确定在特殊人群中预防性使用非甾体类抗炎药(NSAIDs)的最佳剂量和疗程。

芳基烷酸类非甾体抗炎药的手性药动学和药效学研究

非甾体抗炎药(nonsteroidal antiinflammatory drugs,NSAIDs)是一类常见的具有抗炎、解热、镇痛及抗风湿作用的药物,临床应用广泛。大多数芳基烷酸类非甾体抗炎药都具有手性,它们的2个对映体在体内的药理活性、代谢过程及不良反应存在显著的差异。文中对常见芳基烷酸类NSAID对映体的药效学和药动学特点,年龄、性别、疾病状态等因素对其药动学过程的影响,以及临床应用进行了综述。

北京27家医院解热镇痛非甾体抗炎药应用情况

目的:探讨临床用药特点及问题.方法:调查北京地区27家医院1996年解热镇痛非甾体抗炎药的应用情况,进行全面分析.结果:使用总品种88个,10所以上医院使用的品种16个.结论:北京地区27所医院对本类品种的使用是比较科学合理的.

绝经后妇女骨关节炎合并骨质疏松三联治疗的临床观察

目的探讨绝经后妇女骨关节炎合并骨质疏松三联治疗的临床效果。方法选取2017年4月至2018年3月在我院治疗的64例绝经后骨关节炎合并骨质疏松患者进行研究,按照简单随机法将患者分为对照组、观察组,对照组予以非甾体类药物(NSAID)+玻璃酸钠治疗,观察组予以NSAID+玻璃酸钠+依降钙素治疗。比较两组患者的治疗效果及治疗前后VAS评分、Lysholm膝关节评分、WOMAC评分、腰骨密度值变化。结果对照组患者治疗有效率为78.13%,观察组治疗有效率为93.75%,观察组患者治疗有效率高于对照组(P<0.05)。两组患者治疗后骨密度高于治疗前(P<0.05);而在治疗后3个月、6个月,观察组患者骨密度高于对照组(P<0.05)。两组患者治疗后VAS评分、Lysholm膝关节评分、WOMAC评分低于治疗前(P<0.05);而在治疗后3个月、6个月,观察组患者VAS评分、Lysholm膝关节评分、WOMAC评分均低于对照组(P<0.05)。结论 NSAID、玻璃酸钠、依降钙素联合应用于绝经后妇女骨关节炎合并骨质疏松治疗,不仅可提高治疗效果,改善膝关节功能,还能提高活动度及患者生活质量,应用于临床可起到积极作用。

局部应用法斯通治疗骨关节及软组织肿痛

目的：评价法斯通凝胶对急性创伤、关节炎或肌腱炎患者的骨关节及肌肉组织肿痛的疗效及安全性。方法：根据受累部位不同，局部应用法斯通凝胶２～４ｇ，ｂｉｄ，共用７ｄ。对照组选用扶他林乳剂，用法及用量同法斯通。结果：法斯通凝胶能有效改善关节及软组织的肿胀和压痛，总有效率为６０．７％，显效率７．８％，有效率５２．９％，其中对ＲＡ和ＯＡ的总有效率为４１．９％，对良性创伤的总有效率为９０％，与扶他林乳剂比较两者在总有效率和慢性关节炎（ＲＡ＋ＯＡ）有效率方面无显著性差异，而对良性创伤治疗方面，前者优于后者（Ｐ＞０．０５）。结论：法斯通可用于治疗各种原因引起的关节及软组织肿痛，特别是对急性创伤效果更佳。对需全身用药的慢性关节炎，可作为一种辅助治疗用药。

环氧酶选择性抑制剂筛选模型的建立

目的 建立COX1和COX2活性检测模型 ,为COX2选择性抑制剂的筛选及抗炎作用机制研究提供可靠方法。方法 COX1抑制剂筛选模型用新生小公牛主动脉内皮细胞为酶源 ,6 keto PGF1α的含量变化评价化合物对COX1的抑制作用。COX2抑制剂筛选模型用激活的小鼠腹腔巨噬细胞 ,PGE2 含量变化评价化合物对COX2的抑制作用。结果 Indomethacin可显著地抑制COX1的活性 ,Meloxicam可显著地抑制COX2的活性 ,其对COX2的选择性抑制作用高于前者。结论 COX1和COX2抑制剂筛选模型可用于COX2选择性抑制剂的筛选和机制研究。

非甾体抗炎新药联苯乙酸的合成

联苯经乙酰化制得乙酰联苯,再经Willgerodt反应和水解制得联苯乙酸。

COX-2和iNOS在实验性大鼠肺癌发生发展中的表达及其与微血管密度的关系

目的 探讨环氧化酶 2蛋白 (COX 2 )和诱导型一氧化氮合酶蛋白 (iNOS)在肺癌发生发展中的表达及其与肿瘤血管生成的关系。方法 Wistar大鼠 88只 ,“左肺叶支气管灌注致癌质碘油”法诱发肺鳞癌 ,分批处死 ,获取肺鳞癌发生发展各阶段标本 ,以 10只正常大鼠作为对照。用免疫组化法检测标本中COX 2、iNOS的表达和MVD值。结果 共获取 15 5例病变组织 ,其中 14例支气管粘膜增生 ,2 5例鳞状化生 ,33例不典型增生 ,12例原位癌 ,5 4例浸润癌 ,17例转移癌。不典型增生 (2 .1± 1.9)与鳞状化生 (0 .6± 0 .9)比较、原位癌 (3.7± 2 .4)与不典型增生比较、转移癌 (5 .9± 3.2 )与浸润癌 (3.8± 2 .7)比较 ,COX 2表达评分差异均有显著性 (P <0 .0 1,P <0 .0 5 ,P <0 .0 1)。支气管粘膜增生 (3.7± 2 .1)与正常粘膜 (0 .5± 0 .7)比较、转移癌 (9.1± 4.0 )与浸润癌 (5 .3± 3.7)比较 ,iNOS表达评分差异均有显著性 (P <0 .0 5 ,P <0 .0 1)。原位癌 (31.7±13.3)与不典型增生 (6.2± 4.0 )比较、浸润癌 (4 7.8± 15 .7)与原位癌比较、转移癌 (64 .4± 2 7.7)与浸润癌比较 ,MVD值差异均有显著性 (P <0 .0 1,P <0 .0 1,P <0 .0 1)。COX 2与iNOS表达呈正相关 (r =0 .60 16,P<0 .0 0 1)。MVD与COX 2。