Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

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>

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.

Treatment of refractory depression patients of yin deficiency inner heat syndrome by jieyu granule combined paroxetine: an efficacy observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the efficacy of jieyu granule (JG) combined Paroxetine in treating refractory depression (RD) patients of yin deficiency inner heat syndrome (YDIHS).</p><p><b>METHODS</b>Seventy RD patients of YDIHS were randomly assigned to the experimental group (JG combined Paroxetine) and the control group (Chinese medical placebo combined Paroxetine), 35 cases in each group. Hamilt Depression Rating Scale and Hamilton Anxiety Scale were used before treatment, and at the weekend of the 2nd, 4th, and 8th week, respectively.</p><p><b>RESULTS</b>In the experimental group, 32 patients completed the trial and 3 patients dropped out. In the control group, 33 patients completed the trial and 2 patients dropped out. At the end of the 8th week of the treatment, the total score of Hamilt Depression Rating Scale was (14.75 +/- 7.85) in the experimental group, lower than that of the control group (19. 06 +/- 8. 31, P <0.05). At the end of the 2nd, 4th, and 8th week of the treatment, the score of Hamilton Anxiety Scale was 17.03 +/- 4.25, 14.50 +/- 5. 13, and 11.03 +/- 4.88, respectively in the experimental group, lower than that of the control group at each corresponding time point (19. 60 +/-3. 96, 17. 12 +/- 4.14, 14.64 +/- 4.47, P <0.05, P <0.01).</p><p><b>CONCLUSION</b>The efficacy of JG combined Paroxetine for treating RD patients of YDIHS was superior to that of using Paroxetine alone.</p>

Clinical study on a randomized, double-blind control of Shenwu gelatin capsule in treatment of mild cognitive impairment / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of Shenwu gelatin capsule (compound Chinese ginseng and fleeceflower root etc) in the treatment on senile mild cognitive impairment.</p><p><b>METHOD</b>166 patients meeting criteria for mild cognitive impairment were selected from patients in Dongzhimen Hospital and were randomly assigned into a treatment group (n = 83 cases), given 5 capsules of Shenwu gelatin capsule, and a positive control group (n = 83 cases) , given 2 capsules of aniracetam with 3 placebo capsules. All subjects took this medication 3 times a day for 3 months, double-blind and double-moulding control were used in this study. At a baseline and end (three months later), all subjects were assessed using a battery consisting of MMSE and clinical memory scale (CMS).</p><p><b>RESULT</b>Both Shenwu gelatin capsule and aniracetam can remarkably increase the score of memory quotient (MQ), P < 0. 01. They have the similarly effectiveness, there are no statistical difference between the two groups in effectiveness of increasing memory scores.</p><p><b>CONCLUSION</b>Shenwu gelatin capsule has certain effects on mild cognitive impairment.</p>

A clinical study on a randomized, double-blind control of Chinese medicine granules in treatment of vascular dementia / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of Chinese medicine granules (Compound Chinese extract from herbs) in the treatment on senile vascular dementia.</p><p><b>METHOD</b>One hundred and twenty patients meeting criteria for vascular dementia were selected from patients in Dongzhimen Hospital and were randomly assigned into a treatment group (n = 70 cases), given 1 package of Chinese medicine granules with 1 placebo tablets, and a positive control group (n = 50 cases), given 1 tablets of Duxil with 1 package of placebo. All subjects took this medication 3 times a day for 2 months. Double-blind and double-moulding control were used in this study. At a baseline and end (two months later), all subjects were assessed using a battery consisting of MMSE and Blessed behavior measuring scale.</p><p><b>RESULT</b>Both Chinese medicine granules and Duxil could remarkably increase the score of cognition and activity (P < 0.01). They had Similarly effectiveness and there was no statistical difference between the two groups in effectiveness of increasing memory scores. Chinese medicine granules was better than Duxil in increasing the scores of behavior (P < 0.05).</p><p><b>CONCLUSION</b>Chinese medicine granules has certain effects on vascular dementia. And it has remarkable effectiveness in ameliorating the status of total body. And it can relieve the symptoms in vascular dementia.</p>

Effect of GETO on expression of protein in postsynaptic dense zone of Alzheimer's disease model rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of GETO on expression of PSD-95 and Shank-1 protein in postsynaptic dense zone in Alzheimer disease (AD) model rats.</p><p><b>METHODS</b>The AD model rats were established by beta-amyloid protein (Abeta(1-42)) injection into hippocampus CA1 zone. They were assigned into the model group, the donepezil treated group and the GETO treated group, besides, a normal group was set for control. Four weeks after modeling, Morris water maze test was applied to determine the learning and memory function of the AD rats, the number of PSD-95 and Shank-1 protein positive neuron as well as the optical density (OD) in post-synaptic dense zone of hippocampus CA1 area were determined by using immuno-histochemical stain and computerized graphic analysis techniques.</p><p><b>RESULTS</b>Morris water maze test showed that the mean escape latent period (MELP) of the model rats obviously prolonged than that of the normal rats, and the times of traversing flat roof obviously decreased (P < 0.01), while in the model rats after being treated by GETO, the two parameters were significantly shortened and increased respectively (P < 0.01), reaching the level insignificantly different to those in the donepezil group and the normal group. Immunohistochemical test showed that the number of positive stained neuron of PSD-95 and Shank-1 in hippocampus CA1 zone in the model group was significantly different to those in the normal group (P < 0.01), while in the GETO group those indexes were insignificantly different to those in the donepezil group and the normal group (P > 0.05), but showed a significant difference when compared with those in the model group (P < 0.05).</p><p><b>CONCLUSION</b>GETO can obviously improve the function of learning and memory of AD rats induced by Abeta(1-42), and the mechanism may be associated with its actions in improving expressions of PSD-95 and Shank-1 protein in hippocampus CA1 zone, and recovering the structure and function of synapse and enhancing its plasticity.</p>

Research of kingsbrain on improving the learning and memory ability of MCAO rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the influence of Kingsbrain (GETO) on the learning memory impairment of rats with cerebral ischemia.</p><p><b>METHOD</b>Rats with cerebral ischemia were administered GETO orally once a day for one month. The ability of spatial-learning memory of rats was evaluated by Morris Water Maze (MWM). Duxil was used as a positive control.</p><p><b>RESULT</b>the results of place navigation of MWM showed that at the 3rd time of swimming training, the escape latency of rats of the GETO group, Duxil group and Sham group were shorter than that of model group. The escape latency were (54.1 +/- 43.94), (55.9 +/- 43.49), (50.4 +/- 34.99) and (85.4 +/- 42.8) s, respectively; but there was no significantly difference. After the 6th time of swimming training, the escape latency of rats of the GETO group (37.8 +/- 38.69) s, the Duxil group (37.4 +/- 38.03) s and the sham group (26.9 +/- 21.63) s were significantly shorter than that of model rats (77.5 +/- 47.59) s, P < 0.05, respectively. Comparison of the swimming distance among groups were similar to the escape latency among groups. In the test of spatial probe, results of the ratio of the swimming time of platform quadrant (tP) vs the total swimming time (tT) and the ratio of the swimming distance of platform quadrant (dP) vs the total swimming distance (dT) indicated that the ratios of the GETO group (0.347 +/- 0.0662, 0.344 +/-0.055 1), the Duxil group (0.345 +/- 0.0984, 0.34 +/- 0.0934) and the sham group (0.35 +/- 0.0662, 0.349 +/- 0.0589) were significantly higher than those of the Model group (0.261 +/- 0.0689, 0.274 +/- 0.0544), P < 0.05, respectively.</p><p><b>CONCLUSION</b>GETO can significantly improve the spatial learning and memory ability of rats with cerebral ischemia, which provides the pharmacodynamics evidence for its clinical application of improveing the learning and memory ability in poststroke patients.</p>

Influence of Chinese herbal extract complex on expression of corticotropin-releasing factor and protein kinasec protein in hippocampus of middle cerebral artery occlusion rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the influence of one Chinese herbal extract complex (GETO) on the expression of corticotropin-releasing factor(CRF) and protein kinasec(PKC) proteins of the hippocampus in middle cerebral artery orilusion(MCAO) rats.</p><p><b>METHOD</b>All rats were subjected to MCAO by nylon thread, except the sham-group rats. Rats were divied into four groups: sham-group, cerebral ischemia model-group, GETO-group(6. 1 g x kg(-1) x d(-1) )and Duxil-group (7.3 mg x kg(-1) x d(-1)). Using immunohistochemistry technique we measured the expression quantity of CRF and PKC protein in hippocampus of MCAO rats at 2 h,6 h and 24 h after reperfusion, contrasted to Duxil.</p><p><b>RESULT</b>CRF: There were lots of positive and deeper dyeing neurons in hippocampus of model-group rats, while there were a few of positive and lighter dyeing neurons in sham-group, GETO-group and Duxil-group. The positive expression areas of CRF protein in hippocampus of model-group was significantly bigger than that of sham-group, GETO -group and Duxil-group respectively( P <0. 01). PKC: There were a great number of denser positive granules in hippocampus of model-group rats, while there were a few of scattered positive granules in sham-group, GETO-group and Duxil-group. The positive expression areas of CRF protein in hippocampus of model-group was significantly bigger than that of sham-group, GETO-group and Duxil-group respectively( P < 0. 01). At the same time there was not significant difference about the expression of CRF and PKC protein between GETO group and Duxil-group.</p><p><b>CONCLUSION</b>The high expression of CRF and PKC induced by cerebral ischemia may be one important factor that resulted in the delayed neuronal death in hippocampus. GETO can down-regulate the expression of CRF and PKC induced by cerebral ischemia, which may be one of the mechanisms that the Chinese herbal extract complex, protect cerebral ischemic injury.</p>

The influence of CGE on expression of IL-1beta and c-fos protein in the hippocampus region in rats following cerebral ischemia-reperfusion / 中国中药杂志

<p><b>OBJECTIVE</b>To observe inhibiting effect of CGE (compound ginseng extract) on increased expression of IL-1beta and c-fos protein following cerebral ischemia-reperfusion.</p><p><b>METHOD</b>The vascular dementia model was made by middle cerebral artery occlusion for 2 hours. Expression of IL-1beta and c-fos were determined by immunohistochemistry in the hippocampus regions in brain tissue at the 0.5 h-7 d after reperfusion. CGE was diluted by CMC and poured into the stomach by 0.7 mL x (100 g)(-1) with a high dosage (19.34 x 10(3) g x L(-1) row herbs), a middle dosage (9.67 x 10(3) g x L(-1)), a low dosage (4.83 x 10(3) g x L(-1)). There were an IL-1ra (rhIL-1ra 20 microg injected into the left cerebral ventricle), a sham operation (NaCl 20 microL injected into the left cerebral ventricle) and a model as control.</p><p><b>RESULT</b>Compared with control group, three dose groups (low, middle and high) in CGE showed significant inhibiting effects on the expression of c-fos protein at 2, 3, 4, 12 hours and 3 day following cerebral ischaemic-reperfusion. The level of the inhibiting effects in small and middle groups were lower at all time points than that in IL-1ra group (P < 0.05 to P < 0.01). CGE inhibited the expression of hippocampus IL-1beta protein, taking effect from the 2 h after reperfusion. Both HD group (531 +/- 151.1) and MD group (589.3 +/- 78.6) showed more obvious effect which lasted until the 72 h compared with the model group (687.6 +/- 116.7) (P < 0.01 and 0.05). Large dose group (81.3 +/- 16.1) showed the same level of the inhibiting effect on expression of c-fos protein as IL-1ra group (67.2 +/- 25.7) from 4 hour on following cerebral ischaemic reperfusion (P > 0.05).</p><p><b>CONCLUSION</b>CGE with function of Yiqi Bushen, Huoxue Huatan has effect of inhibiting up-regulated expression of IL-1beta and c-fos protein following cerebral ischemia-reperfusion. However, this effect of CGE starts relatively later than that of IL-1ra. The effect of CGE is associated with its dosage, i.e. a larger dosage has a better effect on expression of c-fos protein in post-stroke dementia.</p>

Clinical study of effect of tianzhi granule on senile vascular demetia / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of Tianzhi Granule (TZK) on senile vascular dementia (VaD), which is classified as sthenia of liver-yang.</p><p><b>METHOD</b>Two hundred VaD patients were treated with TZK (0.5 g/bag), which was taken one bag each, three times a day. The treatment course was one month and they were treated for rwo courses.</p><p><b>RESULT</b>TZK could remarkably increase gnosia and activity, with no striking difference from that of positive control group (P > 0.05). Simultaneously, TZK could significantly improve the clinical syndrome of traditional Chinese medicine and viability. It could also drastically reduce the whole blood and plasma viscosity and improve erythrodegeneration and abnormality of aggregation index in the abnormal blood viscosity patients.</p><p><b>CONCLUSION</b>TMC has certain effects on senile VaD.</p>

A follow-up study on a randomized, single-blind control of King's Brain pills in treatment of memory disorder in elderly people with MCI in a Beijing community / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effect of King's Brain pills (Compound Chinese ginseng extract from herbs) on the treatment and the delaying of memory decline in the elderly with mild cognitive impairment (MCI) in a community by a year follow-up of neuropsychology.</p><p><b>METHOD</b>75 patients with MCI were selected from Beixinqiao community of Beijing by a cutoff score of 0.0/0.5 on CDR and were randomly assigned into a treatment group (n = 30 cases), given 4 pills of a compound Chinese ginseng extract (King's Brain) with 2 placebo tablets, and a positive control group (n = 30 cases), given 2 tablets of Piracetam with 4 placebo tablets, as well as a placebo group (n = 15 cases), given a placebo of 4 tablets and 2 pills. All subjects took this medication 3 times a day for 3 months. Single-blind and double-moulding control were used in this study. At a baseline and a middlepoint (after 3 months), and a follow-up end (one year later) following a three months of medication therapeutics, all subjects were assessed using a battery consisting of MMSE and 5 memory items on BNPT battery.</p><p><b>RESULT</b>In the treatment group, MMSE score 27.50 +/- 1.68 was increased to 28.27 +/- 1.70 after 3 months but decreased to 26.90 +/- 1.90 after one year of the treatment. However, the latter score was higher than that in a placebo group 26.33 +/- 1.03 (P < 0.05). Verbal Learning Test score was significantly increased from 68.73 +/- 28.74 at baseline to 87.33 +/- 29.78 at follow-up point in the treatment group, which was significantly higher than that in the placebo group (P < 0.01). The total score of memory items on BNPT battery was significantly increased from 78.23 +/- 28.98 at baseline to 93.53 +/- 35.56 at follow-up point in the treatment group, higher than that in Piracetam group (P < 0.05) and the placebo group (P < 0.01).</p><p><b>CONCLUSION</b>Both King's Brain spills and piracetam tablets have protective effect on cognitive and memory decline in elderly with MCI.</p>