Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer's Disease / 中国结合医学杂志

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.

Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice.</p><p><b>METHODS</b>Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg•d)], the low, medium and high dosage of GAPT groups [0.075, 0.15, 0.30 g/(kg•d), 12 in each group], and 12 three-month-old C57BL/6J mice were set as a normal control group, treatments were administered orally once a day respectively, and both the normal group and model group were given 0.5% sodium carboxymethyl cellulose solution. Immunohistochemistry (IHC) and Western blot analysis were used to detect the expression of total tau protein (Tau-5), cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in hippocampal neurons of experimental mice after 8-month drug administration (11 months old).</p><p><b>RESULTS</b>In the model group, the expression of Tau-5 and CDK5 were increased, whereas the expression of PP2A was decreased in hippocampal neurons, which were signifificantly different compared with that in the normal group (all P<0.01). IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups, and an increase of PP2A. Compared with the model group, the changes were signifificant in GAPT groups (P<0.05 or P<0.01). Similar results were shown by Western blot.</p><p><b>CONCLUSION</b>GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.</p>

Treatment of vascular dementia by Chinese herbal medicine: a systematic review of randomized controlled trials of clinical studies / 中国中西医结合杂志

<p><b>OBJECTIVE</b>Chinese herbal medicine has been extensively used in the treatment of vascular dementia (VaD), but lacked systematic review on its efficacy and safety. So we conducted a systematic review to assess the efficacy and safety of Chinese herbal medicine in treating VaD.</p><p><b>METHODS</b>CNKI, CBM, PubMed, and Wiley Online Library were retrieved for randomized trials (RCTs) on Chinese herbal medicine treating VaD patients. Randomized parallel control trials by taking Chinese herbal medicine as one treatment method and placebos/cholinesterase inhibitors/Memantine hydrochloride as the control were included. Quality rating and data extraction were performed. RevMan5.2.0 Software was used for meta-analysis. Standardized mean difference (SMD) at 95% confidence interval (CI) was used to indicate effect indicators of results.</p><p><b>RESULTS</b>Seven RCTs met the inclusive criteria. Totally 677 VaD patients were randomly assigned to the treatment group and the control group. Descriptive analyses were performed in inclusive trials. The cognitive function was assessed in all trials. Results showed Mini-Mental state examination (MMSE) score was better in the Chinese herbal medicine group than in the placebo group, but with no significant difference when compared with the donepezil group (P > 0.05). Adverse reactions were mainly manifested as gastrointestinal symptoms such as abdominal pain in the Chinese herbal medicine group. But they occurred more in the donepezil group than in the Chinese herbal medicine group.</p><p><b>CONCLUSIONS</b>The methodological quality of included trials was poor with less samples. Results of different trials were lack of consistency. Present evidence is not sufficient to prove or disapprove the role of Chinese herbal medicine in improving clinical symptoms and outcome indicators of VaD patients. Their clinical efficacy and safety need to be supported by more higher quality RCTs.</p>

Analysis on follow-up efficacy and safety of slow transit constipation treated with individualized deep puncture at Tianshu (ST 25): a multi-central randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the follow-up efficacy and safety on slow transit constipation (STC) treated with individualized deep puncture at Tianshu (ST 25).</p><p><b>METHODS</b>One hundred and twenty-eight cases of STC were randomized into a deep puncture group (64 cases), a western medication group (31 cases) and a shallow puncture group (33 cases) at the ratio of 2:1:1. In the deep puncture group, electroacupuncture of deep puncture was applied to bilateral Tianshu (ST 25). The needle was inserted perpendicularly and slowly at the acupoint and went deeply till penetrating the peritoneum, about 20 to 65 mm in depth. In the western medication group, lactulose oral liquid was prescribed for oral administration. In the shallow puncture group, electroacupuncture of shallow puncture was done at bilateral Tianshu (ST 25). The needle was inserted perpendicularly and slowly, 5 to 8 mm in depth. The treatment lasted 4 weeks in the three groups and the follow-up visit of 12 weeks and 6 month after treatment was performed respectively. The weekly defecation frequency, patient's satisfaction and safety of deep puncture at Tianshu (ST 25) were assessed before and after treatment in each group.</p><p><b>RESULTS</b>In the deep puncture group, the weekly defecation frequency was (1.79 +/- 1.05) times/week before treatment and was (3.90 +/- 1.43) times/week after 4-week treatment. It was (3.49 +/- 1.46) times/week in 12-week follow-up visit after treatment and was (3.51 +/- 1.42) times/week in 6-month follow-up visit after treatment. In the deep puncture group, the improvements in weekly defecation frequency, patient's satisfaction and short-term efficacy were same as those in the western medication group and the shallow puncture group (all P > 0.05). The long-term efficacy in follow-up visit was better remarkably than that in the western medication group (P < 0.05, P < 0.01). Besides, the combined medication was reduced and no adverse reaction occurred.</p><p><b>CONCLUSION</b>The individualized deep puncture at Tianshu (ST 25) is effective in the treatment of STC and achieves the satisfactory long-term efficacy. This therapy displays the good effective advantage and deserves to be promoted in clinical practice of acupuncture and moxibustion therapeutic program as compared with the first-tier line of medication, lactulose oral liquid, recommended at home and abroad, in terms of the evidence-based medicine.</p>

Assessment of the results of syndrome in clinical trials of dementia treated by Chinese herbal medicine / 中国中西医结合杂志

Chinese medical syndrome efficacy, as a second efficacy indicator, has been widely used in clinical trials of treating dementia by Chinese herbal medicine. The syndrome assessment tool is a key point in assessing the efficacy of Chinese medical syndrome. The syndrome assessment tool for dementia used nowadays needs to be optimized in content, reliability, and validity. In this paper, the authors reviewed some problems correlated with the design of Chinese medical assessment questionnaire on the basis of Chinese medical theories by combining the common requirements for questionnaire development.