Efficacy of acupuncture and pharmacological therapies for vascular cognitive impairment with no dementia: a network meta-analysis.

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=331718, identifier: CRD42022331718.

[Association of CYP2C19 and CYP3A5 gene polymorphisms with myocardial infarction].

OBJECTIVE: To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction. METHODS: Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power. RESULTS: The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%. CONCLUSION: CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.

Four New Chromone Derivatives from Colletotrichum gloeosporioides.

Four previously unreported chromones, 5-hydroxy-2-(hydroxymethyl)-8-methoxy-4H-chromen-4-one (1), (5R,7S)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4H-chromen-4-one (2), (5R,7S)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4H-chromen-4-one (3), and (5R,7S)-5,7-dihydroxy-2-[(E)-prop-1-en-1-yl]-5,6,7,8-tetrahydro-4H-chromen-4-one (4), as well as one known analogue 5-hydroxy-2-methyl-4H-chromen-4-one (5) were isolated from the fermentation broth of the endophytic fungus Colletotrichum gloeosporioides derived from the mangrove Ceriops tagal. Their structures were elucidated based on extensive spectroscopic analyses. The absolute configurations of 2-4 were determined by comparison the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 2 showed cytotoxic activity against A549 cell line with the IC50 value of 0.094 mm.

[Observation on therapeutic effect and mechanism research of acupuncture on headache in the recovery phase of ischemic stroke].

OBJECTIVE: To explore the clinical therapeutic effect and mechanism of acupuncture on headache in the recovery phase of ischemic stroke. METHODS: A total of 97 patients with headache in the recovery phase of ischemic stroke were randomized into an acupuncture group (57 cases) and a western medication group (40 cases). In the western medication group, flunarizine hydrochloride capsule was taken orally 5 mg each time, once a day. In the acupuncture group, acupuncture was applied at Qiuxu (GB 40), Zulinqi (GB 41), Xuanli (GB 6), Shuaigu (GB 8), Fengchi (GB 20) and Baihui (GV 20) for migraine; Chongyang (ST 42), Neiting (ST 44), Jiexi (ST 41), Zusanli (ST 36), Hegu (LI 4), Cuanzhu (BL 2) and Baihui (GV 20) for forehead pain; Jinggu (BL 64), Kunlun (BL 60), Tianzhu (BL 10), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for occipital headache; Taichong (LR 3), Yongquan (KI 1), Sanyinjiao (SP 6), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for parietal headache. The needles were retained for 30 min each time, once a day and 5 times a week. Both of the two groups were given consecutive treatment for 14 days. The visual analogue scale (VAS) and the headache scores before and after treatment and the recurrence rate 1 month after treatment were observed to evaluate the therapeutic effect, before and after treatment, the contents of substance P (SP), dopamine (DA), serotonin (5-HT), alpha-endorphin (α-EP) and beta-endorphin (ß-EP) in plasma were determined by ELISA in the two groups. RESULTS: Compared before treatment, the VAS scores, the headache scores and the contents of SP, DA and 5-HT in plasma were reduced and the contents ofα-EP andß-EP in plasma were increased in the two groups (all P<0.01). After treatment, the changes of the VAS score, the headache score and the contents of pain-related factors and endogenous opioid peptides in plasma in the acupuncture group were larger than the western medication group (all P<0.05). The total effective rate in the acupuncture group was 84.2% (48/57), which was superior to 62.5% (25/40) in the western medication group, and the recurrence rate in the acupuncture group was lower than the western medication group (both P<0.01). CONCLUSION: The therapeutic effect of acupuncture on headache in the recovery phase of ischemic stroke is superior to flunarizine hydrochloride capsule, and the mechanism may relate to down-regulate the pain-related factors and up-regulate endogenous opioid peptides in plasma.

[Using bioinformatics tools to explore cellular biological mechanisms of "Triple Energizer Acupuncture Method" in treating senile dementia].

OBJECTIVE: To observe the effect of needling "Danzhong" (CV17), "Zhongwan"(CV12), "Qihai" (CV6), "Xuehai"(SP10)and "Zusanli"(ST36) (Triple Energizer Acupuncture Method) on the learning-memory ability and profile of hippocampal differentially-expressed genes and proteins of SAMP8 mice (rapid aging mice), so as to explore its underlying mechanisms in improving Alzheimer's disease (AD)．. METHODS: A total of 60 SAMP8 were used as the dementia model and randomly divided into blank control, acupoint and non-acupoint groups (n＝20 per group). The 5 acupuncture points and non-acupoints (subcostal region) on the bilateral sides were needled with filiform needles and manipulated manually for 30 s at each one，once daily, 6 times a week for 4 weeks. The Morris water maze tests (location navigation tests and space probing trials) were used to evaluate the mouse's learning-memory ability. The hippocampal tissue was extracted to detect differentially expressed genes and proteins related to acupuncture intervention by gene chip and isobaric tags for relative and absolute quantitation (iTRAQ) techniques as well as bioinformatic analysis, separately. The information is analyzed through bioinformatics database tools. Finally, immunofluorescence staining was used to verify theresults of microarray analysis. RESULTS: Compared with mice of the control and non-acupoint groups, the escape latency of location navigation task of Morris water maze tests on 4th and 5th day of training was significantly shortened in mice of the acupoint group, and the duration of stay in the original safe-platform quadrant was significantly increased in the acupoint group (P<0.05). Gene microarray displayed that in comparison with the control group, 898 differentially expressed genes were up-regulated, 418 genes were down-regulated in the hippocampus of acupoint group. The iTRAQ analysis indicated that in the acupoint and non-acupoint groups, 286 and 299 differentially expressed proteins were up-regulated, 319 and 179 proteins down-regulated, respectively. Of the 34 terms containing 47 proteins up-regulated by acupoint needling, including intermediate filament, keratin filament, myelin sheath, postsynaptic density, neuron projection were related with neurite and cytoskele-ton. While in the non-acupoint group, of the 24 terms were listed by the system, only the myelin sheath involving 11 differentially expressed proteins functions in activities of neurite and cytoskeleton. Immunofluorescence staining of the hippocampal tissue showed that the high-density distribution areas of neurons and neurite fibers were characterized by decentralization and disordering, with the highlighted areas being mainly near the cell body parts in control mice, but in mice of the acupoint group, the highlighted areas at the neurite were relatively dense, the morphology of hippocampal cells was complete, the fiber structure was clear, dense and orderly, and the neurites were closely arranged and in order, indicating an improvement of the distribution and arrangement of nerve fibers after acupuncture. The height of neurite highlight area of the acupoint group was significantly higher than that of the non-acupoint group (P<0.05)．. CONCLUSION: The "Triple Energizer Acupuncture" of acupoints is able to improve the learning-memory ability in SAMP8, which may be related to its effects in regulating the expression and function of hippocampal genes and proteins related to neurite and cytoskeleton.

Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice.

BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P<0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P<0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P<0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P<0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.

[Effect of Acupuncture Plus Moxibustion on Immune Function in Patients with Bra-chiocephalic Takayasu Arteritis].

OBJECTIVE: To observe the influence of acupuncture and moxibustion on humoral immunity and cellular immunity related indexes in patients with bra-chiocephalic Takayasu arteritis (BCTA), so as to explore its underlying mechanisms in the treatment of Takayasu arteritis (TA). METHODS: A total of 31 BCTA patients (9 men and 22 women at age of 16-70 years) were treated by manual acupuncture stimulation of main acupoint Renying(ST 9)and auxillary acupoints as Jiquan (HT 1), Chize (LU 5), Fengchi (GB 20), bilateral Xinshu (BL15), Feishu (BL 13) and Geshu (BL 17), Jingming (BL 1), etc. according to clinical symptoms, with the needles retained for 20 min. Additionally, moxibustion was applied to Taiyuan (LU 9), BL 15, BL 13 and BL 17. The treatment was conducted twice daily for 4 weeks. Serum IgG, IgA, IgM, IgE, C3 , C4 contents, and CD 3＋， CD 4＋， CD 8＋ T lymphocytes contents were assayed by using immue turbidimetry and cell counting. RESULTS: Before the treatment and in these 31 BCTA patients, an abnormal increase was found in serum IgG content in 10 cases, IgM in 3 cases, IgE in 3 cases, C3 in 11 cases, CD 4＋ in 6 cases, and CD 8＋ in 9 cases, and an abnormal decrease was found in serum CD 3＋ level in 11 cases, CD 4＋ in 7 cases, as well as CD 8＋ in 4 cases. After the treatment, the increased levels of IgG, IgM, C3, CD 4＋ and CD 8＋ in patients with abnormally higher values were considerably down-regulated (P<0.05), the decreased levels of CD 3＋， CD 4＋ and CD 8＋ in patients with abnormally lower values were evidently up-regulated (P<0.05). No significant changes were found in IgG, IgA, IgM, IgE, C3 and C4, CD 3＋ and CD 8＋ in patients with normal values of these indexes after the treatment (P>0.05). The CD 4＋ level in patients with normal value was significantly deun-regulated after the treatment (P<0.05), but still in the range of normal value. CONCLUSION: Acupuncture plus moxibustion can regulate some of the abnormally elevated and lowered humoral immunity and cellular immunity related indexes in BCTA patients, possibly having a favorable role in the treatment of BCTA.

Acupuncture improves dendritic structure and spatial learning and memory ability of Alzheimer's disease mice.

Acupuncture can improve the cognitive state of Alzheimer's disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai (CV6), Zhongwan (CV12), Danzhong (CV17), bilateral Zusanli (ST36), and bilateral Xuehai (SP10) acupoints was performed once a day (1-day rest after 6-day treatment) for 14 consecutive days. Senescence-accelerated mouse prone 8 (SAMP8) mice without acupuncture and senescence-accelerated mouse resistant 1 (SAMR1) mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.

Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation.

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 (SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong (CV17), Zhongwan (CV12), Qihai (CV6), bilateral Xuehai (SP10) and bilateral Zusanli (ST36) 15 days before and after implantation of neural stem cells (5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

miR-22 exerts anti-alzheimic effects via the regulation of apoptosis of hippocampal neurons.

To investigate the expression of miR-22 in the hippocampus of amyloid ß (1-42)-induced alzheimic rats, and to assess the underlying mechanism. A total of 60 male Sprague Dawley rats weighing between 274.65 and 293.97 g (mean weight = 284.31 ± 9.66 g) and aged 12 to 14 weeks were randomly assigned to three groups: control group (n = 20), Alzheimer's disease group (AD group; n = 20) and AD + miR-22 mimic group (ADMM group; n = 22). Rat AD model was established by injecting a solution of Aß1-42 into the hippocampal CA1 regions. After 24 h, rats in the ADMM group also received intraventricular injection of miR-22 mimic continuously for 28 days. The escape latency of rats, neuronal damage in the hippocampus, synaptic structure, brain-derived neurotrophic factor (BDNF), and the expressions of apoptosis-related proteins were assessed or determined, as appropriate. The expression of miR-22 in hippocampus of the AD group was significantly lower than that in the control group (p < 0.05). However, after 28 days of intraventricular injection of miR-22 mimic into AD rats, the expression was significantly increased, relative to control (p < 0.05). The escape latency of AD rats was significantly prolonged, and the number of platform sites significantly reduced when compared to the control group (p < 0.05). However, the escape latency was significantly shortened and the number of platform sites significantly increased in the ADMM group, relative to the control and AD groups. Results of transmission electron microscopy showed that the expression of miR-22 significantly reversed the degradation of synaptic structures in the hippocampus of AD rats as evidenced by recovery of abnormal synaptic cleft width and the length of synaptic active zones (p < 0.05). Results of Nissl staining revealed significant proliferation of gliacyte and loss of Nissl bodies. After miR-22 injection, the number of gliacytes in the hippocampus of AD rats was significantly reduced, while the number of Nissl bodies was significantly increased (p < 0.05). The expressions of BDNF in CA1 and CA2/3 regions of AD rats were significantly lower than those in the control group, and BDNF in the hippocampus of AD rats was significantly increased after 28 days of continuous injection of miR-22 (p < 0.05). The positive expression of Tunnel in the ADMM group (22.67 ± 2.96 %) was significantly higher than that in the AD group (4.49 ± 1.23 %), but significantly lower than that of control (39.51 ± 3.66 %) (p < 0.05). After 28 days of intraventricular injection of miR-22 mimic into AD rats, the expression of Bax protein was significantly down-regulated, while bcl-2 protein was significantly up-regulated (p < 0.05). The expression of miR-22 in the hippocampus of patients with AD inhibits neuronal apoptosis, thereby improving learning and memory dysfunction.

Acupuncture for patients with mild to moderate Alzheimer's disease: a randomized controlled trial.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD. METHODS: This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL23) and Neuropsychiatric Index (NPI). RESULTS: Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively. CONCLUSIONS: Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD. TRIAL REGISTRATION: ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

Acupuncture upregulates G protein coupled activity in SAMP8 mice.

BACKGROUND: Transmembrane and intracellular signal transduction of G protein is closely related to the pathophysiology of Alzheimer's disease (AD). OBJECTIVE: To explore the effects of Sanjiao acupuncture on G protein signal transduction pathways in the pathogenesis of AD. METHODS: 36 senescence-accelerated (SAM) prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12) or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was included (SAMR1 group, n=12). Morris water maze tests were used to investigate learning and memory abilities. Immunoprecipitation and Western blotting were used to study expression of G protein subunits and their activities in the cortex/hippocampus. RESULTS: Behavioural analysis showed that acupuncture attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8 mice. The findings of the G protein activation assays via immunoprecipitation and Western blots were that the physiologically coupled activation rate (PCAR) and maximal coupled activation rate (MCAR) of Gαs and Gαi were decreased in the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in the PCAR of Gαs and Gαi. In the hippocampus of untreated SAMP8 mice, the PCAR of Gαs and MCAR of both Gαs and Gαi declined, and Sanjiao acupuncture was associated with an upregulation in the MCAR of Gαs and Gαi. There were no significant differences in Gαs and Gαi expression between the groups. CONCLUSIONS: Sanjiao acupuncture attenuates cognitive deficits in a mouse model of AD via upregulation of G protein activity and stabilisation of the cellular signal.

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. ß/A4(Aß) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aß deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders.

Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer's Disease Treated with Hippocampal Neural Stem Cells.

Transplantation with neural stem cells (NSCs) is a promising clinical therapy for Alzheimer's disease (AD). However, the final fate of grafted NSCs is mainly determined by the host microenvironment. Therefore, this study investigated the role of Sanjiao acupuncture in the NSCs-treated hippocampus of a mouse model, senescence-accelerated mouse prone 8 (SAMP8) using Western blot, real-time fluorescent PCR, and immunofluorescence techniques. Meanwhile, we developed a co-culture model of hippocampal tissue specimens and NSCs in vitro, to observe the effects of acupuncture on survival, proliferation and differentiation of grafted NSCs using flow cytometry. Results showed that acupuncture pre- and post-NSCs transplantation significantly improved senescence-induced cognitive dysfunction (P < 0.05); upregulated the expression of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) (P < 0.05); and also increased the count of neuron-specific nuclear protein (NeuN)- and glial fibrillary acidic protein (GFAP)-positive cells (P < 0.05). Therapeutic acupuncture may regulate the cytokine levels associated with survival, proliferation, and differentiation of NSCs in hippocampal microenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice.

[Clinical research of electroacupuncture at acupoints of qijie area combined with spine balance-regulating massage on posterior circulation ischemia].

OBJECTIVE: To compare the clinical efficacy difference between electroacupuncture (EA) at qijie area combined with spine balance-regulating massage and medication for posterior circulation ischemia (PCI). METHODS: One hundred cases of PCI were randomly divided into a treatment group (50 cases) and a medication group (50 cases). The treatment group was treated with EA at Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shenshu (BL 23), Danzhong (CV 17), etc. in qijie area combined with spine muscle-relieving massage and comprehensive chiropractic. The medication group was treated with oral administration of nimodipine (30 mg per time, three treatments per day) and vinpocetine injection with 500 mL of glucose injection or intravenous drip of 500 mL 0.9% sodium chloride injection, once a day. Ten treatments were taken as one course in both groups, and two courses were given. The symptom score, mean resistance index (RI) of vertebral artery (VA) and basilar artery (BA), mean velocity of blood flow (Vm) and comprehensive clinical efficacy were compared before and after treatment in two groups. RESULTS: The cured and markedly effective rate was 79.6% (39/49) in the treatment group, which was superior to 54.7% (23/42) in the medication group (P<0.05). The symptom score was both significantly improved after treatment in two groups (both P<0.05), which was more obvious in the treatment group (P<0.05). The RI of VA and BA, Vm of VA and BA were significantly improved after treatment in two groups (all P<0.05), which were more obvious in the treatment group (all P<0.05). CONCLUSION: The electroacupuncture combined with spine balance-regulating massage has superior effect on improving mean velocity of blood flow and resistance index of vertebral artery and basilar artery as well as symptom score to medication, and is believed to be a safe and effective treatment for posterior circulation ischemia.

[Clinical research of primary trigeminal neuralgia treated with electroacupuncture at qi streets acupoints combined with spinal regulation therapy].

OBJECTIVE: To compare the difference in the clinical efficacy on primary trigeminal neuralgia (PTN) between the comprehensive therapy of electroacupuncture (EA) at qi streets acupoints combined with spinal regulation method and medication with carbamazepine (CBZ). METHODS: Sixty patients were randomized into a comprehensive therapy group (30 cases) and a medication group (30 cases). In the comprehensive therapy group, the acupoints at qi streets on the head such as Taiyang (EX-HN 5) and Sishencong (EX-HN 1) and those at qi streets on the chest and abdomen such as Shenshu (BL 23), Zhongwan (CV 12) and Guanyuan (CV 4), etc. were selected. After arrival of qi, EA was attached on 2 to 4 groups of acupoints. After acupuncture, the spinal regulation method was applied. This comprehensive therapy was given once a day. In the medication group, CBZ was used for oral administration, 100 mg at the first time, twice a day, and 400 to 600 mg each day as the maintenance dose. Separately, before and after treatment, in 2 and 6 months in follow-up, pain rating index (PRI), life satisfaction index B (LSI-B) and hamilton depression scale (HAMD) were adopted to evaluate comprehensively the clinical efficacy in the two groups and compare the adverse reaction during the treatment between the two groups. RESULTS: After treatment, the curative and markedly effective rate in the comprehensive therapy group was 76.7% (23/30), which was better than 63.3% (19/30) in the medication group (P < 0.01). The difference in PRI was not significant after treatment between the two groups (all P > 0.05). In 2 and 6 months follow-up, PRI grade in the comprehensive therapy group was superior to that of the medication group (both P<0. 05). After treatment and in follow-up, HAMD score was all reduced in the two groups (P < 0.01, P < 0.05) and the result in follow-up in the comprehensive therapy group was significant as compared with that in the medication group (all P<0. 05). After treatment, LSI-B score was increased obviously in the two groups (all P < 0.05) and the result in the comprehensive therapy group was better than that in the medication group (P < 0.05). The incidence of adverse reaction in the comprehensive therapy group was 16.7% (5/30), which was lower than 30.0% (9/30, P < 0.01) in the medication group. CONCLUSION: The comprehensive therapy of EA at qi streets acpoints combined with spinal regulation method achieves the long-term efficacy on PTN as compared with oral administration of CBZ in terms of the improvement of psychological condition, analgesia and life quality. It is the safe, effective and stable therapy.

[Effect of acupuncture on transmembrane signal pathway in AD mice: an analysis based on lipid-raft proteomics].

OBJECTIVE: To reveal the transmembrane signal pathway participating in regulating neuron functions of treating Alzheimer's disease (AD) by acupuncture. METHODS: SAMP8 mice was used for AD animal model. The effect of acupuncture method for qi benefiting, blood regulating, health supporting, and root strengthening on the amount and varieties of transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice was detected using HPLC MS/MS proteomics method. RESULTS: Compared with the control group, acupuncture increased 39 transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice, of them, 14 belonged to ionophorous protein, 8 to G protein, 8 to transmembrane signal receptor, and 9 to kinase protein. Totally 3 main cell signal pathways were involved, including G-protein-coupled receptors signal, enzyme linked receptor signal, and ion-channel mediated signal. Compared with the sham-acupuncture group, acupuncture resulted in significant increase of kinase signal protein amount. From the aspect of functions, they were dominant in regulating synapse functions relevant to cytoskeleton and secreting neurotransmitters. CONCLUSION: The cell biological mechanism for treating AD by acupuncture might be achieved by improving synapse functions and promoting the secretion of neurotransmitters through transmembrane signal transduction, thus improving cognitive function of AD patients.