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1.
目的探讨沙利度胺单药及联合应用5-氟尿嘧啶(5-FU)+奥沙利铂对肝癌细胞株SMMC7721生长的影响。方法采用MTT法检测确定各个单药的IC50,并以药物的IC50作为后续实验的给药浓度。实验分为空白对照组、沙利度胺组、5-FU+奥沙利铂组及沙利度胺联合5-FU+奥沙利铂组。MTT法检测各组药物作用24 h及48 h后对肝癌细胞的抑制率。各组药物作用48 h后,采用流式细胞术检测细胞周期,RT-PCR法测定SMMC7721细胞的Bcl-2、Bax mRNA的表达,Western blot法分析Bcl-2、Bax蛋白的表达。结果 MTT结果显示,药物作用24、48 h后,沙利度胺能够明显抑制肝癌细胞SMMC7721的增殖,促进其凋亡(抑制率分别为14.86%和24.24%),而沙利度胺联合5-FU+奥沙利铂的抑制作用更加显著(抑制率分别为29.80%和40.53%),呈现时间依赖性。药物作用48h后,三个用药组的肝癌细胞均被阻滞于G0/GI期,且沙利度胺联合5-FU+奥沙利铂组的阻滞作用更为明显(P0.05)。沙利度胺下调Bcl-2基因表达而上调Bax基因表达,且沙利度胺联合5-FU+奥沙利铂对Bcl-2、Bax基因的调控作用更为显著,差异均有统计学意义(P0.01)。结论沙利度胺能够明显抑制SMMC7721细胞的增殖,且与5-FU及奥沙利铂具有协同作用,其机制可能与影响Bcl-2及Bax的表达有关。  相似文献   

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目的 研究白桦脂酸(betulinic acid)对鼻咽癌细胞CNE-1生物学行为的影响并探讨其可能机制.方法 不同浓度(10、20、40、80、120、160 μg/mL)白桦脂酸处理CNE-1细胞,作用不同时间(24、48、72 h)后,MTT法检测CNE-1细胞增殖变化;不同浓度白桦脂酸(10、20、40 μg/mL)作用CNE-1细胞72 h后,流式细胞仪PI单染法和FITC-AnnexinⅤ/PI双染法检测细胞周期和凋亡变化;RT-PCR检测凋亡相关基因Bcl-2和Bax mRNA表达水平的变化;Western blot 检测Bcl-2和Bax蛋白表达水平的变化.结果 MTT实验显示不同浓度白桦脂酸对CNE-1细胞均有抑制作用(均P<0.05),抑制效果呈时间和剂量依赖性,24、48和72 h的IC50分别为(37.46±2.51),(24.28±1.87),(21.15±1.42)μg/mL;流式细胞术结果显示10、20、40 μg/mL白桦脂酸组与空白组比较均出现G0/G1期阻滞[(59.21±2.47)%、(72.20±4.28)%、(77.13±3.57)% vs (42.94±2.63)%,均P<0.05]和凋亡比例的增加[(14.95±2.11)%、(21.71±2.84)%、(38.49±3.26)% vs (4.02±0.96)%,均P<0.05];RT-PCR结果显示对照组与白桦脂酸20、40 μg/mL组的Bcl-2与内参β-actin吸光度积分值之比(Bcl-2/β-actin)随白桦脂酸浓度增加而减小,而Bax与内参β-actin吸光度积分值之比(Bax/β-actin)随白桦脂酸浓度增加而增加;Western blot结果显示白桦脂酸下调抑凋亡基因Bcl-2蛋白的表达,同时上调促凋亡基因Bax蛋白表达.结论 白桦脂酸通过介导细胞G0/G1期阻滞和诱导细胞凋亡抑制鼻咽癌细胞CNE-1增殖.其诱导凋亡作用可能与下调Bcl-2/Bax表达比例相关.  相似文献   

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王瑾  宋珂珂  马肖容  张王刚  何爱丽 《西部医学》2019,31(12):1814-1819,1825
目的 观察CpG ODN对人急性单核细胞白血病细胞株U937化疗敏感性的影响,探讨增强急性白血病化疗效果的可能途径及其作用机制。〖HTH〗方法〖HTK〗 多柔比星(ADM)单药及联合应用CpG ODN与U937细胞共同孵育,采用CCK-8法检测U937细胞生长抑制率,Hoechst染色法和流式细胞仪Annexin V-PI双染法检测U937细胞的凋亡情况,RT-PCR检测分析凋亡相关基因Bcl-2和Bax的水平。 结果 ADM对U937细胞生长具有明显抑制作用,而且CpG ODN与其联合应用可进一步加强该作用。各浓度ADM+CpG ODN联合组对U937细胞的生长抑制率和诱导的早期凋亡率均显著高于ADM单药组(均P<0.05)。ADM+CpG ODN联合组细胞内Bax基因的mRNA表达量较ADM单药组明显上升(P<0.05),而Bcl-2 mRNA的表达无显著性差异(P>0.05)。ADM+CpG ODN联合组较ADM单药组的Bcl-2/Bax值减小(P<0.05)。 结论 CpG ODN可增强ADM对U937 细胞生长的抑制作用,加强ADM诱导白血病细胞凋亡的作用,从而增强U937对ADM的化疗敏感性。该作用可能是通过上调Bax基因的表达而实现。  相似文献   

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祁敏芳  吴慧娟  郑贞苍  徐挺立  林露 《浙江医学》2020,42(22):2388-2392,2407
目的探讨绞股蓝总苷(Gyp)对缺氧/复氧(O/R)小鼠海马HT22细胞p21活化蛋白激酶1(PAK1)、环磷酸腺苷反应单元结合蛋白(CREB)表达及凋亡的影响。方法将小鼠海马HT22细胞分为正常对照组、O/R组、70mg/LGypO/R组、85mg/LGypO/R组和100mg/LGypO/R组后,4组细胞建立O/R模型。观察细胞形态学变化;采用流式细胞仪检测各组细胞凋亡率;Westernblot法测定各组B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、PAK1、CREB蛋白表达水平。结果正常对照组细胞贴壁生长,细胞膜光滑、完整,胞体折光性强,细胞突触明显,突触之间相互交织成网状;O/R组细胞贴壁不紧,细胞膜皱缩,胞质凝聚,细胞胞体突触明显减少,细胞间连接大量减少;70mg/LGypO/R组、85mg/LGypO/R组、100mg/LGypO/R组细胞上述现象依次缓解。与正常对照组相比,O/R组细胞凋亡率、Bax、Bax/Bcl-2蛋白表达水平均升高(均P<0.05),Bcl-2、PAK1、CREB蛋白表达水平均降低(均P<0.05);与O/R组相比,70mg/LGypO/R组、85mg/LGypO/R组、100mg/LGypO/R组细胞凋亡率、Bax、Bax/Bcl-2蛋白表达水平依次降低(均P<0.05),Bcl-2、PAK1、CREB蛋白表达水平依次升高(均P<0.05)。结论Gyp可能通过上调小鼠海马HT22细胞PAK1、CREB蛋白表达水平来抑制细胞凋亡。  相似文献   

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目的 探讨沙利度胺对子宫内膜异位症(EMT)患者内膜间质细胞(ESC)的增殖、迁移运动、修复及体外侵袭能力的影响及其作用机制.方法 体外原代培养EMT患者的ESC,加入不同浓度沙利度胺(500.00、250.00、125.00、62.50、31.25μg/ml)分别作用24 h、48 h后,应用噻唑蓝法测定ESC的抑制率.另取ESC分为空白组(沙利度胺0μg/ml)、15 μg/ml沙利度胺组、30 μg/ml沙利度胺组,分别应用划痕实验、Transwell小室实验测定沙利度胺对ESC迁移运动及修复能力、体外侵袭能力的影响,流式细胞仪检测在沙利度胺作用24 h后ESC的凋亡率,酶联免疫吸附试验实验检测沙利度胺对ESC血管内皮生长因子(VEGF)蛋白表达的影响.结果 15、30 μg/ml沙利度胺组细胞的迁移及修复能力、穿膜细胞数较空白组下降,细胞凋亡率较空白组升高(P<0.05);细胞抑制率随沙利度胺作用的浓度升高而升高(P<0.05);15、30 μg/ml沙利度胺组细胞VEGF蛋白表达量明显低于空白对照组(P<0.05).结论 沙利度胺可抑制人EMT患者ESC的增殖、迁移运动和体外侵袭能力,并可以诱导细胞凋亡,其机制可能是下调细胞VEGF蛋白分泌.  相似文献   

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李跃文  万强 《中国全科医学》2018,21(32):3971-3975
目的 探讨甘草总黄酮对阿司匹林损伤人胃黏膜上皮细胞(GES-1)的保护作用及可能机制。方法 2017年3—11月,选取GES-1细胞株,分为6组,对照组:加DMEM培养基;阿司匹林组:阿司匹林18.5 mmol/L与GES-1共同培养24 h;甘草总黄酮低组、甘草总黄酮中组、甘草总黄酮高组:GES-1分别以甘草总黄酮(3、6、12 mg/L)预处理2 h后再加阿司匹林18.5 mmol/L共同培养24 h;PD98059组:GES-1以甘草总黄酮12 mg/L预处理2 h后,加PD98059 10 μmol/L处理1 h,再加阿司匹林18.5 mmol/L共同培养24 h。采用MTT法检测细胞增殖抑制率,采用流式细胞术检测细胞凋亡率,检测乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,采用Western blotting法检测细胞磷酸化细胞外调节蛋白激酶(p-ERK1/2)、B淋巴细胞癌2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达。结果 与对照组比较,阿司匹林组、甘草总黄酮低组、甘草总黄酮中组、甘草总黄酮高组、PD98059组细胞增殖抑制率、细胞凋亡率、LDH活性、MDA含量、p-ERK1/2、Bax表达升高,SOD活性、Bcl-2表达降低(P<0.05);与阿司匹林组比较,甘草总黄酮中组、甘草总黄酮高组、PD98059组细胞增殖抑制率、细胞凋亡率、LDH活性、MDA含量、p-ERK1/2、Bax表达降低,SOD活性、Bcl-2表达升高(P<0.05);与甘草总黄酮低组、甘草总黄酮中组、甘草总黄酮高组比较,PD98059组细胞增殖抑制率、细胞凋亡率、LDH活性、MDA含量、p-ERK1/2、Bax表达降低,SOD活性、Bcl-2表达升高(P<0.05)。结论 甘草总黄酮可通过促增殖、抗凋亡、抗氧化应激等途径减轻阿司匹林诱导的GES-1损伤,其机制可能与抑制ERK1/2信号通路有关。  相似文献   

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目的 探讨苍耳亭对白血病细胞的抗癌作用及其机制是否与调控长链非编码RNA(lncRNA)类赖氨酰氧化酶1反义RNA1(LOXL1-AS1)和微小RNA(miR)-520d-5p表达有关。方法 按转染细胞分组:对照组、苍耳亭6 μmol/L组、苍耳亭20 μmol/L组、苍耳亭60 μmol/L组、si-NC组、si-LOXL1-AS1组、苍耳亭+pcDNA-LOXL1-AS1组;采用细胞计数试剂盒(CCK-8)法、流式细胞术检测细胞增殖和凋亡。实时定量PCR(RT-qPCR)检测LOXL1-AS1和miR-520d-5p表达;蛋白质印迹法检测B细胞淋巴瘤(Bcl)-2和Bcl相关x蛋白(Bax)蛋白表达。分别转染LOXL1-AS1小干扰RNA、LOXL1-AS1过表达载体至K-562细胞中,通过CCK-8法、流式细胞术、蛋白质印迹法分析干扰LOXL1-AS1表达或过表达LOXL1-AS1联合苍耳亭对K-562细胞增殖、凋亡以及Bcl-2、Bax蛋白表达的影响。双荧光素酶报告实验分析LOXL1-AS1和miR-520d-5p相互作用。结果 苍耳亭处理后K-562细胞增殖抑制率、凋亡率、Bax蛋白表达、miR-520d-5p表达显著升高(均P<0.05),Bcl-2蛋白表达、LOXL1-AS1表达显著降低(均P<0.05)。干扰LOXL1-AS1表达后K-562细胞增殖抑制率、凋亡率、Bax蛋白表达、miR-520d-5p表达显著升高(均P<0.05),Bcl-2蛋白表达显著降低(P<0.05)。过表达LOXL1-AS1明显减弱苍耳亭处理对K-562细胞细胞增殖、凋亡以及Bcl-2和Bax蛋白表达的影响。LOXL1-AS1与miR-520d-5p直接结合。结论 苍耳亭可抑制白血病细胞增殖,诱导其凋亡,其机制可能与抑制LOXL1-AS1/miR-520d-5p轴有关。  相似文献   

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目的 观察神经酰胺(ceramide,Cer)对人胃癌耐顺铂(cisplatin,DDP)细胞的耐药逆转作用并对其机制进行初步探讨.方法 体外培养SGC7901/DDP细胞后给予外源性Cer及DDP干预,通过MTT、流式细胞仪观察肿瘤细胞增殖、凋亡、周期阻滞情况,免疫细胞化学染色检测细胞Bcl-2、Bax蛋白表达的改变.结果 单独使用DDP 2.5 mg/L、Cer 2.5 μmol/L组细胞增殖、周期阻滞、细胞凋亡、蛋白表达与对照组相比无统计学差异.Cer 2.5 μmol/L预处理后给予DDP 2.5 mg/L可抑制细胞增殖,作用均强于单独使用Cer及DDP组;Cer 5 μmol/L联合DDP 2.5 mg/L组作用强于Cer 2.5 μmol/L联合DDP 2.5 mg/L组.Cer 2.5 μmol/L+DDP 2.5 mg/L组凋亡率为(19.898±2.003)%,与对照组[(11.930±1.973)%]相比有统计学差异(P〈0.05),与单独使用Cer及DDP组相比也有统计学差异(P〈0.05).Cer 2.5 μmol/L预处理后给予DDP 2.5 mg/L Bcl-2表达下降、Bax表达上调,Bcl-2/ Bax比值下降,与单独使用Cer及DDP组相比有统计学差异(P〈0.05).Cer 2.5 μmol/L预处理后给予DDP 2.5 mg/L出现细胞周期阻滞作用,G0/G1期细胞增多,S期细胞减少,与单独使用Cer及DDP组相比出现统计学差异(P〈0.05).结论 Cer逆转了DDP的耐药作用,其中Cer逆转了DDP的凋亡耐药与改变Bcl-2/Bax比值有关.  相似文献   

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目的:探讨沙利度胺对卵巢癌细胞株SKOV-3的增殖抑制以及凋亡的影响,为后续临床治疗及基础研究提供依据。方法:采用MTT法测定不同浓度沙利度胺作用于SKOV-3细胞株24 h后的吸光度,测定其对SKOV-3的增殖抑制率,Tunel染色法鉴定细胞凋亡,流式细胞术检测细胞凋亡,Q-PCR法检测caspase3 mRNA表达水平,Western Blot法检测caspase3蛋白表达水平。结果:沙利度胺的浓度从31μg/m L增加至500μg/m L时,对于SKOV-3的增殖抑制率从6.22%上升至86%;300μg/m L沙利度胺处理SKOV-3 24 h后,流式细胞术检测其凋亡率上升为52.66%,明显高于空白对照(P<0.01)。Tunel法在荧光显微镜下观察,沙利度胺组可见大片绿色荧光。同时,沙利度胺处理后的SKOV-3的caspase3 mRNA及蛋白表达量与空白对照组相比也明显上升(P<0.01)。结论:沙利度胺能够抑制卵巢癌细胞SKOV-3的增殖并且能够诱导其凋亡。  相似文献   

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Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

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Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

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FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.  相似文献   

19.
In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.  相似文献   

20.
Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.  相似文献   

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