周乐年运用通补法治疗慢性腹泻经验

通补法,即寓通于补,是名中医周乐年在治疗脾胃病方面的重要思想之一。本文主要讨论了通补法在慢性腹泻病因病机的认识、治则治法的确定以及具体遣方用药方面的重要意义,以给临床医师更多的启发。

Therapeutic Effect of Chang'an Ⅰ Recipe(肠安Ⅰ号方) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial

Objective： To evaluate the efficacy and safety of Chinese medicine （CM） decoction Chang＇an I Recipe （肠安 Ⅰ号方） in the treatment of irritable bowel syndrome with diarrhea （IBS-D）. Method： A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang＇an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score （IBS-SSS） and the differences in adequate relief （AR） responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life （IBS-QOL） and Hospital Anxiety and Depression （HAD） scales. The safety indices included adverse events and related laboratory tests. Results： A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set （FAS）, 191 were included in the per protocol set （PPS）. In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval （CI） for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively （95% CI 16.6%-43.4%）. The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group （FAS： 59.6% vs. 35.5%; PPS： 62.8% vs. 38.1%）. As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups （P〉0.05）. Both anxiety and depression scales of HAD were not significantly different between the two groups （P〉0.05）. No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant. Conclusion： Chang＇an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. （No,ChiCTR-TRC-09000328）

A Randomized, Controlled, Double-Blinded and Double- Dummy Trial of the Effect of Tongjiang Granule （通降颗粒） on the Nonerosive Reflux Disease of and Gan （肝）-Wei （胃） Incoordination Syndrome

Objective： To assess the effectiveness of Tongjiang Granule （TJG, 通降颗粒） on the patients with nonerosive reflux disease （NERD） of Gan （肝）-Wei （胃） incoordination syndrome, its impact on their quality of life, and its safety. Method： A randomized, controlled, double-blinded, and double-dummy method was adopted in the trial. There were 120 NERD patients enrolled in the study and randomly divided into the experiment and control groups, each with 60 patients; drugs were distributed according to the drug number by patients＇ inclusion sequences. In the experiment group, patients were given TJG 10 g and mosapdde citrate dummy 5 mg three times a day, and in the control group, patients were given mosapdde citrate 5 mg and TJG dummy 10 g three times a day. The treatment courses of both groups were 4 weeks. Results： Among 120 included patients, 112 were screened for full analysis set （FAS）, and 105 were screened per-protocol set （PPS）. The results were as follows： （1） the improvement of total scores of symptom in the experiment group （0-4 week） were 15.93 ± 7.88 scores by FAS and 16.22 ±7.75 scores by PPS, and they were 10.43± 10.16 scores and 10.79± 10.27 scores in the control group, respectively. The 95% CI of net scores improvement between the two groups were 2.10- 8.90 scores and 1.92-8.94 scores in FAS and PPS; it was significantly better in the experiment group than that in the control group （P〈0.05）. （2） The improvement of scores of major symptom in the experiment group （0-4 week） were 10.68±5.35 by FAS and 10.89±5.29 by PPS and 7.40±7.41 and 7.60±7.46 in the control group, respectively. The 95% CI of net scores improvement in the two groups were 0.85-5.71 and 0.71-5.69 in FAS and PPS separately, and the improvement in the experiment group was significantly better than that in the control group （P〈0.05）. （3） The total effective rates were 86.0% and 61.8% in the experiment and the control group separately, and the Ridit analysis results showed that it was better in the experiment group （P〈0.05）. （4） The improvement quality of life in the domain of physical functioning and general health in the experiment group was better than that in the control group （P〈0.05）. （5） One case of experiment group caught a cold and recovered in six days without drug suspension. No adverse event was found in the other cases. There was no meaningful safety examination indices change in pretreatment and posttreatment periods in both groups. Conclusion： TJG showed a definite effect on the treatment of NERD with Gan-Wei incoordination syndrome, and it could improve the quality of life of NERD patient without obvious toxic and side effects.

Chang'an Ⅱ Decoction(肠安Ⅱ号方)-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats

Objective To investigate the effect of Chang’an Ⅱ Decoction(肠安Ⅱ号方))-containing serum on intestinal epithelial barrier dysfunction in rats.Methods Tumor necrosis factor(TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium.Caco-2 monolayers were treated with blank serum and Chang’an Ⅱ Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang’an Ⅱ Decoction intragastrically at doses of 0.49,0.98,1.96 g/(kg·d)for 1 week,respectively.After preparation of containing serum,cells were divided into the normal group,the model group,the Chang’an Ⅱ-H,M,and L groups(treated with 30 ng/mL TNF-αand medium plus 10%high,middle-,and low-doses Chang’an Ⅱ serum,respectively).Epithelial barrier function was assessed by transepithelial electrical resistance(TER)and permeability of fluorescein isothiocyanate(FITC)-labeled dextran.Transmission electron microscopy was used to observe the ultrastructure of tight junctions(TJs).Immunofluorescence of zonula occludens-1(ZO-1),claudin-1 and nuclear transcription factor-kappa p65(NF-κBp65)were measured to determine the protein distribution.The mRNA expression of myosin light chain kinase(MLCK)was measured by real-time polymerase chain reaction.The expression levels of MLCK,myosin light chain(MLC)and p-MLC were determined by Western blot.Results Chang’an Ⅱ Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α.It alleviated TNF-α-induced morphological alterations in TJ proteins.The increases in MLCK mRNA and MLCK,MLC and p-MLC protein expressions induced by TNF-αwere significantly inhibited in the Chang’an Ⅱ-H group.Additionally,Chang’an Ⅱ Decoction significantly attenuated translocation of NF-κBp65 into the nucleus.Conclusion High-dose Chang’an Ⅱ-containing serum attenuates TNF-α-induced intestinal barrier dysfunction.The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κBp65.

A Preparation Model of Chinese Medicine Decoction Placebo

Chinese medicine（CM）decoction placebo is one of the key factors restricting the placebo-controlled clinical trial of CM.In this article,based on the analysis of the difficulties in preparing CM placebo,the production requirements for placebo were put forward.Moreover,in accordance with clinical practices,a production method and evaluation process of CM decoction placebo was proposed,to provide a reference for clinical research.

以硼替佐米为主的不同化疗方案治疗多发性骨髓瘤的疗效观察

目的探讨硼替佐米+环磷酰胺+地塞米松(PCD)方案与标准或减低剂量的硼替佐米+表柔比星+地塞米松(PAD)方案治疗多发性骨髓瘤(MM)的疗效及对并发症的影响。方法选取2016年7月至2019年6月间辽宁省健康产业集团阜新矿平安医院收治的87例初治或复发难治性MM患者进行回顾性研究。按治疗方法不同进行分组,其中,采用PCD方案治疗的31例患者纳入PCD组,采用标准PAD方案治疗的27例患者纳入标准PAD组,采用低剂量PAD方案治疗的29例患者纳入低剂量PAD组。观察比较三组患者的疗效、感染及化疗不良反应。结果三组初治多发性骨髓瘤患者的深度缓解率比较,差异无统计学意义(P>0.05)。三组复发难治多发性骨髓瘤患者的深度缓解率比较,差异无统计学意义(P>0.05)。三组多发性骨髓瘤患者的总深度缓解率比较,差异无统计学意义(P>0.05)。低剂量PAD组胃肠道症状、感染及周围神经病变发生率均明显低于PCD组,PCD组的血小板减少发生率则明显低于标准PAD组及低剂量PAD组,差异均有统计学意义(均P<0.01)。结论PCD治疗与标准及低剂量PAD治疗MM的疗效相当,但低剂量PAD治疗后的感染、胃肠道反应及神经毒性等不良反应明显少于其他两种方案。