基于生物信息学方法分析影响胆管癌发生发展的差异基因

目的：通过生物信息学的方法挖掘基因综合表达数据库(GEO)中影响胆管癌(cholangiocarcinoma,CCA)发生发展的核心基因,并分析其生物学功能,为CCA的诊断、治疗和评估预后提供理论依据。方法：分析来自GEO数据库中的3个微阵列数据集(GSE32879、GSE45001和GSE76297)。使用GEO2R进行在线差异基因的分析,DAVID进行差异基因的GO 和KEGG 通路分析。使用STRING和Cytoscape进行蛋白互作网络分析(PPI)和枢纽基因(HUB)的筛选。结果：共筛选出151个上调基因,通过PPI筛选出连接度最高的10个基因,分析发现APOA1、AGXT、F13B、FETUB、FERPINC1、SLC2A2这些枢纽基因过度表达与胆管癌的不良预后相关。结论：通过生物信息学探索的枢纽基因可能在胆管癌的发生发展中起着重要作用,并为进一步研究胆管癌的分子机制提供了一定的理论依据。     

结直肠癌差异基因筛选及功能预测

目的 基于美国癌症肿瘤基因图谱（TCGA）数据库分析结直肠癌组织及正常组织的差异表达基因,并探讨其相关分子机制。方法 从TCGA数据库下载所有结直肠癌中mRNA转录组数据。共包含样本740例,其中,结直肠癌组织为571例,正常组织为169例。在R语言环境下,采用edge R工具包处理数据,得到差异表达基因。利用DAVID数据库对差异表达的前1 000个基因进行GO分析及KEGG通路富集分析。对显著差异表达的前200个差异表达基因进行分析,基于Cysctoscape绘制蛋白互作网络图。比较关键基因在癌组织及正常组织中的表达水平。以关键基因的中位表达水平为界值,将关键基因分为高表达组与低表达组,比较高表达组与低表达组的生存情况。结果 共筛选出5 073个差异表达基因,其中,上调基因2 136个,下调基因2 937个。GO分析结果显示,其生物过程主要在细胞增殖、转运、rRNA加工、受体介导的内吞作用等功能富集。KEGG富集分析结果表明,差异表达基因的信号通路主要有细胞周期、转录失调、胆汁分泌、甲状腺激素信号通路、血小板活化等信号通路。筛选出的前7位关键基因为PLK1、BRD4、EHMT2、HIST2H4B、PRPF19、SUV39H1、TRIM28。进一步分析显示,癌组织中PLK1、PRPF19、SUV39H1表达均高于正常组织（P <0.05）。从生存分析曲线可知,PLK1和SUV39H1高表达组总生存时间与低表达组比较,差异无统计学意义（P >0.05）;HIST2H4B低表达组总生存时间高于HIST2H4B高表达组（P <0.05）。结论 基于TCGA数据库分析出PLK1在结直肠癌组织中高表达,其参与细胞增殖、有丝分裂细胞周期的G2/M转换等生物过程,通过P53信号通路发挥作用,在结直肠癌的发生、发展中起重要作用,有望成为诊断结直肠癌的肿瘤标志物。     

基于生物信息学筛选分析脓毒症预后相关核心基因

目的 基于生物信息学分析影响脓毒症预后的潜在核心基因。方法 利用基因表达数据库(Gene Expression Omnibus,GEO)筛选到脓毒症患者的基因表达数据集GSE54514和GSE65682,通过加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)和维恩分析筛选与脓毒症预后相关的关键基因,采用Metascape数据库、RcisTarget包和CIBERSORT算法进行基因功能富集分析、转录因子富集分析及免疫浸润分析。选取数据集GSE5772进行验证,筛选与脓毒症预后相关的核心基因并使用Kaplan-Meier法进行生存分析。结果 对数据集GSE54514、GSE65682分别进行WGCNA分析,筛选出与脓毒症预后相关性最高的“绿色”和“棕色”模块,并对两个模块的基因取交集,维恩分析得到20个关键基因。这些关键基因主要富集在细胞形态调节、单核细胞迁移等通路上。转录因子富集分析显示转录因子ZNF148可能是基因集的主要调控因子之一。进一步通过数据集GSE5772验证,发现基因FGD3、MBP、MSN、RNF130和SETD1B在脓毒症患者中明显低表达(P＜0.05)。免疫浸润分析表明这5个核心基因均与免疫细胞含量密切相关,其中只有FGD3、MSN和RNF130的表达与脓毒症患者的生存率相关(P＜0.05)。结论 基于生物信息学分析筛选到与脓毒症预后相关的5个核心基因,这些基因与免疫细胞密切相关,其中基因FGD3、MSN和RNF130可能是脓毒症预后的重要预测因子。     

转移性结直肠癌患者总生存期的相关新基因APOH、KNG1和FGG

目的 通过生物信息学方法探讨结直肠癌转移的分子机制，为结直肠癌转移提供潜在的治疗靶点。方法 从高通量基因表达数据库（GEO）下载GSE41568数据集，用Limma软件包筛选转移性和原发性结直肠癌的差异表达基因；通过加权基因共表达网络分析（WGCNA）筛选与结直肠癌不同转移部位相关的核心模块和核心基因；使用STRING和Cytoscape构建蛋白质-蛋白质相互作用（PPI）网络；利用PROGgenesV2数据库进行预后分析。通过基因集富集分析（GSEA）预测基因参与结直肠癌的潜在分子机制。结果 共获得1 159个差异表达基因，由703个上调基因和456个下调基因组成。共表达模块中，前50个核心基因的基因本体（GO）功能富集分析表明，基因主要与创伤反应和急性炎症反应相关。通过PPI网络筛选的3个核心基因APOH、KNG1和FGG对结直肠癌患者的预后有显著影响。结论 APOH、KNG1和FGG与结直肠癌患者的预后呈负相关，这些基因有望成为结直肠癌的诊断生物标志物或治疗靶点。     

乳腺癌中KIF4A基因表达的临床意义及基因富集分析

目的 探讨驱动蛋白超家族4A （kinesin family member 4A,KIF4A）在乳腺癌中的表达及与临床病理特征、预后的关系。方法 利用GEO数据库的GSE3494公共数据集和TCGA数据库的乳腺癌样本及其临床资料,采用χ²检验进行KIF4A与临床病理特征的相关性分析,Kaplan-Meier法进行生存分析。通过基因富集分析预测乳腺癌中高表达KIF4A所富集的基因集。结果 KIF4A在不同Elston组织学分级和TNM分期的乳腺癌肿瘤样本中表达差异有统计学意义（P=0.000）。GSE3494和TCGA数据库中KIF4A与ER水平、PR水平均显著相关（P=0.000）;与年龄仅TCGA数据库分析结果差异有统计学意义（P=0.000）。此外,GSE3494数据集中,KIF4A与肿瘤大小、淋巴结浸润均显著相关（P=0.000）;TCGA数据库中,KIF4A仅与T分期显著相关（P=0.000）,与N分期（P=0.081）、M分期（P=0.372）均不相关。KIF4A高表达的乳腺癌患者预后较差,其疾病特异生存期（P=0.001）和总体生存率（P=0.005）均远低于KIF4A低表达患者,且富集了与细胞分裂、细胞周期调控、DNA复制及DNA损伤修复有关的基因集。结论 KIF4A与乳腺癌多个临床病理指标相关,可作为潜在的乳腺癌预后标志物和治疗靶标进一步研究。     

基于大数据的前列腺癌生物信息学分析

【目的】利用生物信息学的方法,对GEO和TCGA两个基因组学数据库进行分析,探究与前列腺癌相关的差异基因及相关的调控网络。【方法】综合GEO数据库的前列腺癌基因表达芯片数据（GSE46602、GSE55945）和TCGA数据库的RNA-seq数据,利用GEO2R及R语言的edgeR包进行基因差异分析,获得共同的显著差异基因,结合R语言的clusterProfiler包进行GO功能分析及KEGG通路分析,同时利用string网站进行蛋白互作网络分析,筛选出前列腺癌中调节蛋白表达量的关键基因,再结合TCGA临床随访数据分析关键节点基因的临床预后价值。【结果】获得共同差异基因共278个,其中表达上调100个,表达下调178个,它们与上皮细胞的调节增殖、含苯化合物的代谢过程等功能以及谷胱甘肽代谢和粘着斑等信号通路密切相关。蛋白互作网络分析结果得出3个重点蛋白表达模块以及12个关键节点基因。在这些关键基因中,EDN3、EDNRB和AMACR与前列腺癌患者的生存率密切相关。【结论】通过对前列腺癌基因芯片和RNA-seq数据的生物信息学分析,我们发现EDN3、EDNRB与AMACR很可能在前列腺癌的发生发展过程中发挥重要作用。     

ITGA2基因在胰腺癌中表达和临床意义的生物信息学分析

目的：　通过生物信息学方法研究ITGA2（integrin alpha-2）基因在胰腺癌中的表达情况、表达与预后的关系、表达与临床病理特征的关系,并进一步预测ITGA2的生物学功能。方法：　使用GEPIA在线工具分析肿瘤基因组图谱（The Cancer Genome Atlas,TCGA）中ITGA2基因在胰腺癌组织和正常组织中的表达差异,并回顾性分析表达水平与生存预后的关系。利用LinkedOmics数据库筛选ITGA2在胰腺癌中的共表达基因列表,在WebGestalt数据库中分析生物学功能。下载TCGA数据库中胰腺癌患者临床信息和ITGA2表达数据,分析ITGA2表达量与临床病理特征的关系,研究影响胰腺癌生存预后的危险因素。结果：　ITGA2在胰腺癌组织中显著高表达（P<0.05）;与低表达患者相比,ITGA2高表达的胰腺癌患者的总体生存期（log-rank P=0.002）、无病生存期（log-rank P=0.004）明显降低。利用LinkedOmics找出278个与ITGA2共表达的基因,GO分析显示这些基因主要参与细胞黏附、细胞间连接组成、细胞骨架形成等生物过程;KEGG分析显示显著富集于黏着斑、黏附连接、紧密连接、肌动蛋白细胞骨架的调节、肿瘤蛋白聚糖等通路。ITGA2表达水平与肿瘤分期（χ²=6.380,P=0.036）、肿瘤大小或侵袭范围（χ²=5.214,P=0.022）、肿瘤分化程度（χ²=11.998,P=0.002）显著相关具有统计学意义。Cox回归分析结果显示,ITGA2表达水平是影响胰腺癌患者预后的独立危险因素（HR=1.888,95%CI=1.021~3.490,P=0.043）。结论：　ITGA2基因与胰腺癌发生发展密切相关,可作为临床判定胰腺癌预后的标志物,并有成为肿瘤治疗靶点的潜力。     

生物信息学分析胰腺癌组织关键基因表达及其意义

目的 利用生物信息学方法对GEO数据库进行探索,获取胰腺癌发生、发展的核心基因,分析胰腺癌发生、发展的潜在机制。方法 使用GEOquery包从GEO数据库获取胰腺癌相关芯片数据(GSE62452),利用Limma包进行差异分析,结合clustreProfiler包对上调基因和下调基因分别进行GO功能和KEGG通路分析,利用String在线网站对差异基因进行蛋白互作网络分析,利用Cystoscopes软件筛选出核心基因,最后借助TCGA数据库和芯片数据(GSE28735)对核心基因进行再次验证。结果利用生物信息学方法共获得286个差异基因,其中包含上调基因189个,下调基因97个。富集分析结果显示上调基因涉及细胞组织黏附、细胞外基质组织构成等功能以及蛋白消化与吸收、PI₃K-Akt等信号通路相关。下调基因与脂类消化、细胞壁破裂等功能和胰腺分泌等信号通路密切相关。通过蛋白互作网络筛选出20个关键基因,利用GEPIA数据库对关键基因进行生存分析验证,发现3个基因(MMP11、LAMB3、PLAU)与胰腺癌预后明显相关。结论 通过生物信息学方法最终筛选出3个核心基因,为胰腺癌的诊断和预后提供了新的思路。     

利用加权基因共表达网络挖掘乳腺癌相关疾病靶标

目的 利用公共数据库癌症基因组图谱（TCGA）,通过加权基因共表达网络分析（WGCNA）挖掘乳腺癌诊断年龄和肿瘤分期相关疾病靶标。方法 利用TCGA得到53例亚洲人种和126例非洲人种乳腺癌基因芯片表达数据及相应的临床指标,然后用R软件的WGCNA包分别构建这2个人群的共表达网络,得到与诊断年龄和肿瘤分期的相关显著性模块,并用在线网站DAVID进行功能富集,用在线网站UALCAN进行生存分析。结果 WGCNA分析得到11个与肿瘤分期和诊断年龄显著相关的模块。将11个模块取交集后得到42个候选基因,利用在线网站DAVID进行基因本体（GO）富集分析,发现这些候选基因主要富集在蛋白质结合功能方面。取42个候选基因中9个由WGCNA识别出的核心基因,输入在线网站UALCAN上行差异分析和生存分析,最终筛选出2个（ERLIN2和ASH2L）候选生物标志物,这2个基因在正常组织和癌组织中的表达差异有统计学意义（P<0.01）,且表达水平影响乳腺癌患者的生存期（P<0.05）。结论 利用数据挖掘寻找生物标志物或疾病靶标是一种高效、经济的研究方式。本研究通过数据挖掘发现ERLIN2和ASH2L为乳腺癌的候选生物标志物,可用于大样本临床验证及机制探讨。     

利用生物信息学分析食管腺癌的核心基因和通路

目的：　探讨食管腺癌（esophageal adenocarcinoma，EAC）的核心基因及通路。方法：　结合GEO数据库分析EAC与正常食管组织间的差异表达基因。利用多种在线分析软件对中枢基因进行功能富集、通路分析、构建蛋白质互作网络及挑选核心基因。结合TCGA、Oncomine肿瘤数据库对核心基因进行验证以及绘制受试者工作特征（receiver operating characteristic，ROC）曲线、计算曲线下面积（area under the curve，AUC）。结果：　4个GEO数据集分析得出中枢基因共141个，富集在细胞外基质中，主要通过糖酵解、糖异生通路和酪氨酸、组氨酸、苯丙氨酸、β-丙氨酸代谢通路。筛选出3个核心基因，COL1A2的AUC为0.707~0.954；TIMP1的AUC为0.795~0.984；MMP1的AUC为0.896~1.000。结论：　利用生物信息学方法筛选出与EAC相关的核心基因及通路，有助于EAC的早期分子诊断与基因靶向治疗。     

Value of D-Dimers in patients with acute aortic dissection

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.     

Research of combined liver-kidney transplantation model in rats

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.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

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…     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

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.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

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.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.