国医大师葛琳仪辛勤耕耘于杏林六十载,临证倡三位合一,衷正本清源,主用药简练,力求量少轻灵、法捷效速.治肺系病,善用清法,倡衷中参西、分期论治;治脾胃病,立论和法,重视气机斡旋;治老年病,主补虚泻实;治疑难杂病,主正本清源;治未病,重视体质辨识,以"适龄以养""适体以调"为原则.积淀诸多验方医案,文章将葛老临证常用之验方清肺止咳方、降逆平喘方、理气和胃方作一简单介绍.

肺结节是指位于肺内的单发或多发直径≤3cm的类圆形或不规则形病灶,不伴有肺门及纵隔淋巴结肿大、肺不张或肺炎等其他疾病[1-2].大部分肺结节患者,临床无明显的咳嗽、咳痰、胸闷气急等呼吸系统症状,既往研究也显示,96.4％的孤立肺结节多为肉芽肿、错构瘤等良性病变[3].中医文献中无"肺结节"病名及直接论述,故可将其归为"积聚""肺积"等范畴.国医大师葛琳仪悬壶六十余载,擅长诊治肺系疾病、脾胃病和老年病,对肺结节的诊治积累了丰富的临床经验.笔者有幸师承葛老师,随师伺诊,获益良多,现将葛老师运用"清化"法诊治肺结节经验浅析如下.

咯血是肺系疾病中常见病证,其血由肺或气管而来,经口咳嗽而出,表现为痰中带血,或痰血相间,甚或纯血鲜红.现代医学中,支气管扩张、肺结核等都是引起咯血的最常见病因[1-2].支气管扩张是指慢性气道损伤引起支气管壁肌肉和弹力支撑组织破坏所导致的一支或多支支气管不可逆扩张[3].葛琳仪教授为第三届国医大师,第二、第六批全国老中医药专家学术经验继承工作指导老师,擅长肺系疾病、脾胃病及疑难病证的诊治.笔者有幸侍学于侧,获益良多.现将葛老运用"清法"治疗支气管扩张伴咯血的经验浅述如下.

糖尿病周围神经病变(DPN)是糖尿病(DM)患者常见的慢性神经系统并发症之一,发病率占DM患者的40％ ～70％,好发于中老年人,常见症状为肢体麻木、疼痛、灼热或其他异常感觉,严重时可发生溃疡或肢端坏疽等严重并发症,致残及死亡率较高[1-2].DPN的发病机制十分复杂,大多数学者认为其发病机理主要与高血糖、山梨醇旁路、肌醇耗竭、炎症因子异常、蛋白质非酶糖基化、微循环障碍和脂质过氧化等相关[3-4].硫辛酸是一种的强效抗氧化剂,可抑制脂质过氧化,减轻神经组织的氧化应激,维持神经内膜血流和神经传导速度,达到治疗DPN的目的,但部分DPN患者治疗后效果欠理想[5-6].近年来随着中医药的发展,中医外治法在DPN的治疗上显现出明显优势[7].笔者采用外用自拟活血化瘀方联合硫辛酸用于DPN患者,取得了较好疗效,报道如下.

[目的]整理分析葛琳仪教授(以下简称葛老)治疗消化系统肿瘤术后胃肠功能紊乱的特色经验.[方法]通过随师门诊,整理相关医案,从病因病机、辨证论治、用药特色等方面总结分析葛老治疗消化系统肿瘤术后胃肠功能紊乱的临证经验,并列举验案一则加以说明.[结果]葛老认为本病的病机主要可以归为:“脾胃虚弱,中焦失和”“情志郁结,肝失疏泄”和“内生诸邪,郁滞不解”三方面,治疗上以健脾和中为基础,常用六君子汤加减,再佐以柴胡、木香、枳壳、佛手、苍术、厚朴、当归、丹参等药物疏肝理气、豁痰化瘀.所举验案中患者辨为脾胃虚弱证,葛老拟健脾和中法随证加减,疗效显著.[结论]葛老以健脾和中为基础,辅以疏肝理气、豁痰化瘀等方法治疗消化系统肿瘤术后胃肠功能紊乱疗效显著,颇具特色,具有重要临床意义.

第三届国医大师葛琳仪教授悬壶50余载,在治疗多囊卵巢综合征(PCOS)方面积累了丰富的临床经验.葛琳仪提出肝郁气滞、肾精不足及痰湿困脾为该病基本病因病机,并通过融辨病、辨体(质)、辨证为一体之“三位合一”的多元思辨模式进行诊治,取得了良好的临床疗效.

[目的]通过对国医大师葛琳仪(以下简称葛老)学术思想的总结,传承其学术经验,以供广大中医学者参考学习.[方法]亲身采访葛老,根据其本人的回忆及相关著作探求其治学方法;通过跟师抄方及葛老言传身教,传承其辨证论治的临床经验;收集临床病例,经过临床用药组方分析、归纳用药特点等方式总结其遣方用药特色;综合学生与患者对葛老的评价,展现其高尚的医德医风.[结果]葛老辛勤耕耘于杏林数十载,成果丰硕.治学上主张博采众长,知行合一;辨证上提倡三位合一,融辨病、辨证、辨体于一身;论治上善用“和”法以起沉疴;遣方上衰用药简练,力求量少轻灵、法捷效速;医风上崇以人为本,以德修心.[结论]国医大师葛老之学术思想内涵丰厚,值得后辈中医不断挖掘与传承,从中感悟医者治病、治人之一二.

[目的]评价祛酸胶囊治疗慢性痛风合并高尿酸血症患者的临床疗效和安全性.[方法]采用双盲随机对照的方法,将80例慢性痛风患者按1:1比例随机分成试验组40例(口服祛酸胶囊,2片/次,3次/d)和对照组40例(口服祛酸胶囊模拟剂,2片/次,3次/d),治疗期2个月,随访期3个月.主要疗效指标为治疗前后血尿酸(serum uric acid,SUA)水平的差值,次要疗效指标为两组受试者痛风发作次数、SUA达标率(SUA水平降低到360μmol·L-1以下的患者比例).以上指标在治疗前、治疗后以及随访期检测.[结果]最后完成试验并纳入统计的受试者为69例,其中试验组35例、对照组34例,两组患者的一般资料和基线值具有可比性(P>0.05).通过对两组受试者治疗前后的SUA差值进行独立样本t检验,结果显示组间差异有统计学意义(t=2.28,P=0.026).两组患者的痛风发作次数、SUA达标率比较均无统计学差异(P>0.05).肝肾功能检测结果和不良反应总结提示祛酸胶囊具备较好的安全性.[结论]祛酸胶囊可以明显降低受试者的SUA水平,具备较好的安全性.

系统性红斑狼疮(SLE)是一种自身免疫性疾病,以女性多见.近年来,人们对SLE免疫学发病机制研究有了新的进展,诸多研究显示:Th17/Treg细胞免疫失衡参与了SLE异常免疫应答过程[1-2].解毒祛瘀滋阴方是范永升教授治疗SLE的经验方,已证实具有良好的临床疗效.本研究以Th17/Treg细胞免疫失衡为切入点,探讨解毒祛瘀滋阴方对这一免疫平衡的调控作用.

痛风是一种尿酸钠盐沉积所致的晶体相关性关节病,与嘌呤代谢紊乱所致的高尿酸血症(HUA)直接相关.急性痛风性关节炎(AGA)是痛风最常见的临床表现之一,发作时以四肢远端关节非对称的急性红肿热痛为主要特征,常反复发作,后期易引起肾功能损害、关节畸形等.中医学对AGA的认识和诊治具有悠久的历史和丰富的经验,现做一综述.

笔者在临床治疗中采用清热为主,佐以养阴作为治疗大法,运用以"清热养阴丹"为基础方的清热养阴法治疗口腔溃疡,取得较好的临床疗效.很多研究发现中药比如黄连、灵芝、麦冬等可以直接与肠道菌群相互作用,改善肠道微生态结构和多样性,发挥对机体的代谢调控作用[1-3].因此,笔者推测清热养阴丹具有直接调控肠道菌群的作用,这可能是清热养阴丹治疗口腔溃疡的重要原因之一.故用实验研究加以验证.

Objective To evaluate the clinical efficacy of Jiawei Simiao Pills in treating acute gouty arthritis (AGA).Methods Sixty patients with AGA were randomly divided into a western medicine group and a Chinese and western medicine group,with 30 cases in each group.The western medicine group was given Diclofenac Sodium Sustained Release Tablets orally,75 mg each time,once a day,and Sodium Bicarbonate Tablets,1000 mg each time,3 times a day orally.The Chinese and western medicine group was given Jiawei Simiao Pills in addition to the treatment same as in the western medicine group.The patients in the two groups were both treated for 3 days.During the treatment,if the joint pain got worse,patients switched to be treated with glucocorticoids after judgment.Before and after treatment,levels of white blood cells (WBC),C reactive protein (CRP),alanine aminotransferase (ALT),aspartate aminotransferase (AST),blood uric acid (UA),and serum creatinine (Cr) were tested,and scores of joint pain,joint redness and swelling were evaluated respectively.The proportion of patients switching to glucocorticoids was compared between the two groups.Results There were 2 cases in the Chinese and western medicine group switching to glucocorticoids,significantly lower than 9 cases in the western medicine group (P ＜ 0.05).After treatment,levels of WBC,CRP,and UA,as well as scores of joint pain and joint swelling in the Chinese and western medicine group were significantly lower than that before treatment (P ＜ 0.01),and levels of CRP and UA,as well as scores of joint pain,joint redness and swelling were all lower than those in the western medicine group (P ＜ 0.05).Conclusion Jiawei Simiao Pills could inhibit inflammatory reaction,relieve joint swelling and pain symptoms,and reduce the use of glucocorticoids in the treatment of AGA.

Objective To explore the effects of kaempferol(KPF) on renal tissues and to elucidate its underlying inflammatory molecular mechanism in db/db mice.Methods Twenty-four male db/db mice were randomly divided into four groups:Two groups were orally administered a low or high dose of KPF (50 or 200mg/kg,respectively),one control group and one positive control (metformin hydrochloride 0.2g/kg) group.Six male db/m mice were set as normal control group.After 10 weeks treatment,24 hour urinary albumin excretion (UAER) 、SCr were detected;the gene expression of tumor necrosis factor-α (TNF-α),and interleukin-6 (IL-6) were measured by real time PCR;the protein expression of IKKα、phospho-IκBα、phospho-NF-κBp65 were evaluated by Western blotting.Results After 10 weeks of KPF treatment,the urinary albumin excretion,SCr,IL-6 and TNF-αwere reduced,the gene expressions of TNF-α and IL-6 were inhibited.Importantly,the protein expression level of IKKα、phospho-IκBα、phospho-NF-κBp65 in renal tissue was significantly decreased (P ＜ 0.01、0.05).Conclusions Kaempferol has protective effects on renal tissues through inhibiting NF-κB pathway and related inflammation in db/db mice.

Objective] To observe the therapeutic effect of"Modified Simiao Pill"in the treatment of acute gouty arthritis(AGA) and to explore the mechanism of "Modified Simiao Pill"based on the"TLR4/NF-kB"signal pathway.[Methods] 108 SD male rats were randomly divided into normal group, model group, colchicine group,"Modified Simiao Pill"low,medium and high dose groups, 18 rats in each group. Except the normal group, the rest rats were established as AGA model by injecting monosodium urate(MUS) into the knee joint cavity according to Coderre method, after 4 days of treatment, the calculation of each time point tested joint swelling index, the pathological changes of synovial tissue were observed by optical microscope, and the content of IL-1βand TNF-αin joint cavity washing liquid was detected by ELISA method;Immunohistochemistry was applied to measure the expression of TLR4, NF-kB and p-NF-kB protein in synovial tissues. RT-PCR was used to detect the expression of TLR4mRNA in synovial tissues. [Results] Compared with the normal group, model group of rat knee joint swelling index was significantly increased(P<0.01), synovial tissue inflammatory changed obviously, and the expression of TLR4, NF-kB and p-NF-kB protein and TLR4mRNA in synovial tissue was significantly increased(P<0.01), the contents of IL-1βand TNF-αin the washing fluid of the joint cavity were significantly increased(P<0.01).Compared with the model group,"Modified Simiao Pill"high and medium dose group rats knee of joint swelling index decreased significantly(P<0.01), synovial tissue inflammatory changes were alleviated significantly, and the expression of TLR4, NF-kB and p-NF-kB protein and TLR4mRNA in synovial tissue was significantly decreased(P<0.01), the contents of IL-1βand TNF-αin the washing fluid of the joint cavity were significantly decreased(P<0.01).[Conclusion]"Modified Simiao Pill"may be through inhibiting the "TLR4/NF-kB"signaling pathway, thereby inhibiting the production of IL-1βand TNF-αto play a role in the treatment of AGA, and the therapeutic effect is in a dosage-dependent manner.

Objective To explore the mechanism of hypoglycemic effect of GLP-1 on the regulation of intestinal flora. Methods 40 SD male rats were randomly divided into normal group,model group,metformin group and GLP-1 group,10 rats in each group. In addition to the N group, the other rats were fed with high fat diet for 8 weeks and intraperitoneal injection of STZ according to the 30mg/kg for type 2 diabetes model. MET and GLP-1 group were treated respectively with metformin and GLP-1,N and M groups were subcutaneous injected with normal saline for 6 weeks, then collected of rat feces to intestinal flora 16SrDNA sequence. Results Compared with N group,the fasting blood glucose of M,MET and GLP-1 group rats were significantly elevated(P<0.01);compared with M group,MET and GLP-1 group were significantly decreased(P<0.01),and no significant difference between the two groups(P<0.01).The 3 indexes of observed species,shanno,and chao were N grouP>GLP-1 grouP>MET grouP>M group. Compared with N group,the 3 indexes' difference of M group and MET group had statistical significance(P<0.01),while only Chao index difference of GLP-1 group had statistical significance(P<0.01). Compared with the N group,the proportion of Bacteroidetes of M group was significantly decreased(P<0.01),and the proportion of Proteobacteria and Firmicutes were significantly increased(P<0.01).Compared with the M group,the proportion of Bacteroidetes of GLP-1 group was significantly increased(P<0.01),and the proportion of Proteobacteria was significantly decreased(P<0.01).Compared with N group,the proportion of Lactobacillus and Bifidobacterium of M group were significantly decreased(P<0.01),and the proportion of Escherichia and Streptococcus were significantly increased(P<0.01).Compared with M group, the proportion of Lactobacillus and Bifidobacterium of GLP-1 group were significantly increased(P<0.01),and the proportion of Escherichia and Streptococcus were significantly decreased(P<0.01). Conclusion GLP-1 may increase the species diversity of the intestinal flora of T2DM rats,and increase the proportion of probiotics such as Lactobacillus and Bifidobacteria,thus playing a role in regulating blood glucose.

葛琳仪主任中医师系浙江中医药大学教授、硕士研究生导师，第二批全国名老中医药专家学术经验继承工作指导老师。悬壶50余载，临证强调中医“知常善变”和“治病求本”的辨证观，精通内、外、妇、儿各科，尤擅“糖尿病”等内分泌系统疾病诊治。葛老师临床治疗2型糖尿病，必因证制宜，综合运用脏腑及气血津液辨证，对其病因病机、治则、处方用药有独到的见解，取得良好的临床疗效。笔者有幸随师侍诊，获益匪浅，现将葛老师临床经验整理总结如下。

葛琳仪系全国老中医药专家学术经验继承工作指导老师,临证经验丰富.葛老治疗肺系疾患时,擅用“清”法贯串始终,如清宣法、清降法、清润法、清补法等,取效良好.现结合医案将葛老用清法治疗肺系疾病经验整理如下.

葛琳仪教授为国家级名老中医,临证50年擅治疑难杂症,尤其对于病情复杂的头痛及老年病,独具匠心,用药精练得当,常收奇效;笔者有幸随师侍诊,获益匪浅,现将葛老师体会心得一隅总结如下,以飨同道.

目的:观察人参皂苷对实验性自身免疫性甲状腺炎大鼠血清甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6的影响.方法:40只Wistar大鼠随机分为5组,每组8只,即正常组、模型组、人参皂苷低、中、高剂量组.除正常组外,其余4组以猪甲状腺球蛋白造模,造模成功后,人参皂苷各剂量组以相应剂量人参皂苷灌胃,正常组及模型组以蒸馏水灌胃,8周后酶联免疫法检测TGAb、TPOAb、TNF-α及IL-6的水平.结果:与正常组比较,模型组的TGAb、TPOAb显著增加(P＜0.05).与模型组比较,人参皂苷各剂量组TGAb、TPOAb均下降,其中低剂量与中剂量有显著性意义(P＜0.05),高剂量组差异无显著性意义(P＞0.05).与正常组比较,模型组TNF-α显著增加(P＜0.05);与模型组比较,人参皂苷各剂量组的TNF-α均下降,差异均有显著性意义(P＜0.05);但各剂量组间比较,差异无显著性意义(P＞0.05).与正常组比较,模型组的IL-6显著下降(P＜0.05);与模型组比较,人参皂苷各剂量组IL-6均有所上升,但差异均无显著性意义(P＞0.05).结论:人参皂苷能降低甲状腺自身抗体指标,其作用机制可能通过抑制Th1细胞功能的过度亢进,调节免疫的途径来保护甲状腺组织.

[Objective] To study the relationship between type 2 Diabetes(T2DM) in different TCM syndromes and autoimmune thyroid disease(AITD), guide autoimmune thyroid antibodies screening. [Methods] Select 30 cases for every syndrome including yin deficiency and excess heat syndrome ,damp heat syndrome, qi and yin deficiency syndrome,deficiency of yin and yang syndrome and stagnated blood syndrome. 30 cases of healthy people were selected as the normal control group(NCG). Thyroid function and autoimmune thyroid antibodies were measured and the relationship between TCM syndrome and thyroid function and autoimmune thyroid antibodies were analysed. [Results] The prevalence of hypothyroidism of T2DM group was higher than that of NCG, the prevalence of hypothyroidism of deficiency of yin and yang syndrome was higher than other four syndromes, the positive rates of TPOAb of yin deficiency and excess heat syndrome were higher than other syndromes ,with a significant difference. [Conclusion] Examining autoimmune thyroid antibodies of T2DM especial y of yin deficiency and excessive heat syndrome has great importance to early diagnosis and treatment of T2DM with AITD.