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Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.

Objective: To analyze the regularity of acupoint selection, main acupoints and theoretical basis in acupuncture treatment of urticaria., Methods: Papers collected from the time of establishment of each database to September of 2017 were retrieved from databases CNKI, CBM, VIP and WF by using keywords of "acupuncture" "moxibustion" "blood-letting therapy" "autohemotherapy" "cupping" "acupoint catgut embedding" "auricular points" "acupoint injection" "fire-needle" (or red-hot needle), "dermal needle" "needle-embedding" "urticaria" in both Chinese and English. The collected papers were brought into analysis according to the inclusion and exclusion criteria, from which the prescriptions for acupuncture treatment of urticaria were subjected into descriptive statistical analysis, association rule analysis, and cluster analysis by using Access 2010, Clementine 18.0 and Stata software., Results: Outcomes of analysis indicated that the treatment methods of urticaria with acupuncture and moxibustion, with different emphases, may be classified into eight categories. For treating the exterior syndrome of urticaria, acupoints of the Bladder Meridian, Governor Vessel and Conception Vessel were often employed to harmonize Ying and Wei and to dispel the pathogenic wind, while for treating the interior syndrome, acupoints of the Large Intestine Meridian, Spleen Meridian, and Stomach Meridian were usually used to invigorate the spleen to dispel dampness and to regulate blood circulation. The top five frequently used acupoints were Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), Sanyinjiao (SP 6) and Geshu (BL 17). It was crucial to make use of the specific acupoints with adequate meridian- qi , such as He -Sea points, Back- Shu points, and Yuan -Primary points. There were some fixed forms in the combination of acupoints, including LI 11, SP 10, Dazhui (GV 14) and auricular Lung, Shenmen, Fengxi, Adrenal gland, which had the highest confidence coefficient for the meridian points and ear acu-points, respectively. The outcomes of cluster analysis about the acupoint prescriptions showed that 12 acupoint groups as the SP 6-Hegu (LI 4)-LI 11-SP 10-ST 36, etc. were frequently used., Conclusion: The regularity of acupuncture treatment of urticaria can be discovered using data mining technology, resulting in an in-depth understanding and having a solid theoretical basis.

Vitellogenin (Vg) and vitellogenin receptor (VgR) play important roles in the vitellogenesis of insects. In this study, we cloned and characterized the two corresponding genes (TpVg and TpVgR) in an economically important insect, Thitarodes pui (Lepidoptera: Hepialidae), from the Tibetan plateau. The full length of TpVg is 5566 bp with a 5373 bp open reading frame (ORF) encoding 1,790 amino acids. Sequence alignment revealed that TpVg has three conserved domains: a Vitellogenin_N domain, a DUF1943 domain, and a von Willebrand factor type D domain (VWD). The full length of TpVgR is 5732 bp, with a 5397 bp ORF encoding 1798 amino acids. BLASTP showed that TpVgR belongs to the low-density lipoprotein receptor (LDLR) gene superfamily. Structural analysis revealed that TpVgR has a group of four structural domains: a ligand-binding domain (LBD), an epidermal growth factor (EGF)-precursor homology domain, a transmembrane (TM) domain, and a cytoplasmic domain. In addition, TpVgR has four cysteine-rich LDL repeats in the first ligand-binding site and seven in the second. Quantitative real-time polymerase chain reaction analysis revealed that the expression levels of TpVg and TpVgR are much higher in later pupa than in either the larval or adult stage, implying that the synthesis and uptake of Vg in T. pui occurs in the later pupal stage. These results will help us to understand the molecular mechanism of the reproductive capacity and will provide new insight into the mass rearing and utilization of T. pui.

Background: Carboplatin, an antineoplastic agent, binds DNA and enhances radiotherapy (RT) effects. Carboplatin-loaded hydrogel (oxidized hyaluronic acid/adipic acid dihydrazide) enables the sustained drug release and facilitates the synergistic effect with RT., Purpose: We investigated the effectiveness and convenience of hydrogel carboplatin combined with RT for mice glioma., Materials and Methods: Mouse glioma cells (ALTS1C1) were subcutaneously implanted in the right thigh of C57BL/6 mice on Day 0. The mice were categorized by treatments: sham, hydrogel, hydrogel carboplatin, aqueous carboplatin, RT, hydrogel carboplatin/RT, and aqueous carboplatin/RT. Hydrogel carboplatin (300 μg single dose on Day 7) or aqueous carboplatin (100 μg daily dose on Days 7, 8, and 9) was administered via intratumoral injection. RT was delivered a daily dose of 10 Gy on Days 8 and 9., Results: For mice administered hydrogel carboplatin/RT versus those administered aqueous carboplatin/RT, the 24-day tumor growth control rate and 104-day recurrence-free survival rate were 100% and 50% versus 100% and 66.7% (p = 0.648), respectively. However, mice receiving other treatments showed tumor progression by Day 24 and died within 40 days of tumor cell implantation., Conclusions: Hydrogel carboplatin simplified intratumoral drug delivery and remained the synergistic effects with RT, which is potential for clinical applications., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The acute effect of acupuncture on Alzheimer's disease, i.e ., on brain activation during treatment, has been reported. However, the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear. Therefore, in this study, we performed long-term needling at Zusanli (ST36) or a sham point (1.5 mm lateral to ST36) in a rat Alzheimer's disease model, for 30 minutes, once per day, for 30 days. The rats underwent 18 F-fluorodeoxyglucose positron emission tomography scanning. Positron emission tomography images were processed with SPM2. The brain areas activated after needling at ST36 included the left hippocampus, the left orbital cortex, the left infralimbic cortex, the left olfactory cortex, the left cerebellum and the left pons. In the sham-point group, the activated regions were similar to those in the ST36 group. However, the ST36 group showed greater activation in the cerebellum and pons than the sham-point group. These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease., Competing Interests: Conflicts of interest: None declared.

The needling sensation of Deqi during acupuncture is a key factor of influencing acupuncture outcome. Recent studies have mainly focused on the brain function effects of Deqi in a physiological state. Functional magnetic resonance imaging (fMRI) on the effects of acupuncture at Waiguan (SJ5) in pathological and physiological states is controversial. In this study, 12 patients with ischemic stroke received acupuncture at Waiguan (SJ5) and simultaneously underwent fMRI scanning of the brain, with imaging data of the activated areas obtained. Based on the patient's sensation, imaging data were allocated to either the Deqi group or non-Deqi group. In the Deqi group, the activated/deactivated areas were the left superior temporal gyrus (BA39)/right anterior lobe of the cerebellum and left thalamus. In the non-Deqi group, the activated areas included the medial frontal gyrus of the right frontal lobe (BA11), right limbic lobe (BA30, 35), and left frontal lobe (BA47), while the only deactivated area was the right parietal lobe (BA40). Compared with the non-Deqi group, the Deqi group exhibited marked activation of the right anterior lobe of the cerebellum and right limbic lobe (BA30). These findings confirm that the clinical effect of Deqi during acupuncture is based on brain functional changes. Cerebellar activation may be one of the central mechanisms of acupuncture in the treatment of ischemic stroke.

MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important roles in many biological processes. This study aimed to check if miRNAs were involved in the response to acupuncture in rats. Microarray analysis was performed to compare the miRNA expression profiles of medulla in spontaneously hypertensive rats (SHRs) treated with or without acupuncture. Our microarray analysis identified 222 differentially expressed miRNAs in the medulla of SHRs treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with a significant difference were found in acupuncture-treated SHRs compared to untreated rats. These 23 miRNAs could regulate 2963 target genes which were enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339, miR-223, and miR-145 were downregulated in the medulla of SHRs compared to normotensive rats. Notably, these miRNAs were upregulated to basal levels in the medulla of SHRs treated with acupuncture at taichong in comparison with SHRs receiving acupuncture at nonacupoint group or SHRs without any treatment. Our findings have revealed significant changes of a panel of selective miRNAs in hypertensive rats treated at taichong acupoint. These data provide insights into how acupuncture elicits beneficial effects on hypertension.

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

To date, acupuncture has been widely used despite a lack of solid clinical evidence in the East and West. However, there are few validated in vitro models for the mechanistic studies of acupuncture. We hypothesized that adenosine could be used as a probing tool in the mechanistic studies of acupuncture because of its critical role in the action of acupuncture. Subsequently, we tested this hypothesis using both in vitro and in vivo experiments. First, we found that adenosine stimulation mimicked the effect of acupuncture on microRNA profiling (including miR-339, miR-145 and miR-451) and protein level (including Sirt2) in nerve growth factor-induced differentiated PC12 cells. These miRNA and proteins have been found to be regulated by acupuncture treatment in the brain of spontaneously hypertensive rats. Next, we found that adenosine stimulation downregulated miR-339 expression through adenosine A1 receptor-mediated pathway. Finally, we showed that the concentration of adenosine was actually decreased in the brain of spontaneously hypertensive rats after acupuncture treatment at Taichong acupoint. Taken together, these findings suggest that adenosine could be used as a useful probing tool for acupuncture mechanistic studies, while more validation studies are certainly warranted., (© 2014 Wiley Publishing Asia Pty Ltd.)

Objective: To compare the difference in the clinical efficacy on perennial allergic rhinitis between three nasal points acupuncture therapy and the oral administration of loratadine so as to provide the better acupuncture program in clinical treatment., Methods: Sixty cases were randomized into an acupuncture group (30 cases) and a medication group (30 cases). In the acupuncture group, acupuncture was applied to three nasal points [Yingxiang (LI 20), Yintang (EX-HN 3), Bitong (Extra)] and acupoints selected by syndrome differentiation. Acupuncture was given once every two days, three times a week, for 4 weeks totally. In the medication group, loratadine was prescribed for oral administration, 10 mg every day, for 4 weeks. The symptom and physical sign scores before and after treatment, as well the short-term and long-term efficacy were compared between the two groups., Results: The total effective rate was 96.7% (29/30) in the acupuncture group and was 93.3% (28/30) in the medication group after treatment. The efficacy was similar between the two groups (P>0.05). In follow-up, the total effective rate was 86.7% (26/30) in the acupuncture group, which was better than 56.7% (17/30, P<0.05) in the medication group. The scores of symptoms and physical signs after treatment and in follow-up were all reduced apparently as compared with those before treatment in the patients of the two groups (all P<0.05). The scores of symptoms and physical signs were reduced more apparently in the acupuncture group as compared with those in the medication group in follow-up (all P<0.05)., Conclusion: The acupuncture at three nasal points and the acupoints selected by syndrome differentiation achieves the similar short-term efficacy on perennial allergic rhinitis as compared with the oral administration of loratadine. The acupuncture therapy presents the obvious advantages on long-term efficacy.

Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. In this study, we found that the expression of the ZBED6 and IGF2 were upregulated during C2C12 differentiation. The IGF2 expression levels were negatively associated with the methylation status in beef cattle (P < 0.05). A luciferase assay for the IGF2 intron 3 and P3 promoter showed that the mutant-type 439 A-SNP-pGL3 in driving reporter gene transcription is significantly higher than that of the wild-type 439 G-SNP-pGL3 construct (P < 0.05). An over-expression assay revealed that ZBED6 regulate IGF2 expression and promote myoblast differentiation. Furthermore, knockdown of ZBED6 led to IGF2 expression change in vitro. Taken together, these results suggest that ZBED6 inhibits IGF2 activity and expression via a G to A transition disrupts the interaction. Thus, we propose that ZBED6 plays a critical role in myogenic differentiation.

Objective: To observe changes of brain glucose metabolism by needling at Waiguan (SJ5) in cerebral infraction (CI) patients using 18F-fluorodeoxyglucose (FDG) positron-emission computer tomography (PET/CT), thus exploring its effect and mechanisms., Methods: A total of 21 patients with CI were recruited in this study. The location of lesion was limited to the left basal ganglia by CT or MRI scan. All patients were randomly assigned to three groups. i.e., the acupoint group (Group A), the non-acupoint group (Group B), the blank control group (Group C), 7 in each group. Patients in Group A were needled at right Waiguan (SJ5). Those in Group B were needled at non-acupoint [10 mm beside Waiguan (SJ5)], whereas those in Group C did not receive any treatment. All patients underwent PET/CT head scan. All data were statistically analyzed using SPSS 13.0 Software and SPM8 Software., Results: Compared with Group C, glucose metabolism increased in bilateral superior temporal gyrus (BA38), right superior frontal gyrus (BA9), left cingulate gyrus (BA24), left culmen and pyramid of cerebellum, and right cerebellar tonsil of cerebellum in Group A. Compared with Group C, glucose metabolism increased in bilateral superior frontal gyrus (BA6, BA9, BA10), bilateral middle frontal gyrus (BA6, BA10), left middle frontal gyrus (BA4), bilateral uncus of limbic lobe (BA36, BA38), left cingulate gyrus (BA24, BA31), left posterior cingulate gyrus (BA30), left precuneus (BA7), left inferior parietal lobule (BA4), and left lingual gyrus of occipital lobe (BA18) in Group B. Compared with Group B, glucose metabolism increased in bilateral superior temporal gyrus (BA22, BA38), right inferior frontal gyrus (BA47), left culmen and cerebellar tonsil of cerebellum in Group A. Activated encephalic regions of needling at Waiguan (SJ5) were mainly dominated in the healthy side, bilateral superior temporal gyrus, and right inferior frontal gyrus. Activated encephalic regions of cerebellum were located at the left cerebellar hemisphere, left culmen of anterior cerebella lobe, and bilateral cerebellar tonsil of posterior cerebella lobe., Conclusions: Needling at Waiguan (SJ5) of CI patients induced increased glucose metabolism in local cerebral regions. Functional neuroimaging using PET/CT could directly reflect changes of brain glucose metabolism by acupuncture.

Objective: Acupuncture is beneficial in treating stroke neuropsychiatric symptoms. The present study aimed to identify functional brain response to active acupuncture in patients with unilateral ischaemic stroke using functional MRI (fMRI)., Methods: A total of 10 patients aged 47-65 years with left hemispheric ischaemic stroke received single-session manual acupuncture at the TE5 point of the affected (right) forearm. A 6-min tactile control procedure in which an acupuncture needle tip was alternately touched and removed from the skin at the acupuncture point for 30 s each was performed first, followed by active acupuncture in a blocking paradigm consisting of six 30-s twist blocks of rotation interspersed between six 30-s blocks of rest. A whole brain scan was simultaneously conducted on a 3.0-T imager. Activated and deactivated brain regions during tactile stimulation and active acupuncture relative to rest were obtained via group analysis., Results: Compared to tactile stimulation, needling with twist manipulation modulated many more widespread brain areas. All the brain areas activated and deactivated by active acupuncture relative to tactile stimulation were distributed in the primary sensorimotor and medial frontal cortex of the unaffected, but not the affected hemisphere., Conclusions: Active acupuncture results in lateralisation of functional cerebral response to the contralateral unaffected hemisphere in patients with unilateral stroke. This lateralisation may represent an effect of acupuncture in enhancing a compensatory process by redistributing functions into the intact cortex, particularly in the unaffected hemisphere.

As a member of the basic helix-loop-helix (bHLH) family of transcription factors, Bhlhe40 played an important role in the regulation of adipogenesis, myogenesis and the development of metabolic syndrome. In this study, we investigated the tissue expression patterns and differences of bovine Bhlhe40 gene during three developmental stages. The result showed that Bhlhe40 was ubiquitously expressed in most tissues of cattle. In addition, the expression of bovine Bhlhe40 gene showed a decreasing trend in skeletal muscle and fat during the de- velopmental stages. Then, two novel mutations (EX5 + 114 T>C, L166P and EX5 + 733 A>G, S372S) of bovine Bhlhe40 gene were identified by BamHI and ApaI ACRS PCR-RFLP in 1226 individuals from five indigenous cattle breeds in China. Frequencies of allele C at the BamHI locus varied from 0.210 to 0.340 among breeds, while frequencies of allele G at the ApaI locus varied from 0.030 to 0.114. Association analysis revealed no significant association of ApaI locus with growth traits in Nanyang breed. However, BamHI locus was significantly associated with the average daily lain at 18 months in Nanvans cattle (P < 0.05). This study aimed to lay the groundwork to further study of Bhlhe40 function at myogenesis and adipogenesis in bovine and should significantly contribute to cattle breeding and genetics through MAS program.

As a zinc-finger protein, PR domain containing 16 (PRDM16) controls brown fat determination by stimulating brown fat cell production while suppressing the expression of genes for production of white fat cells; mutations in this domain are associated with myelodysplastic syndrome and leukemogenesis. In our study, polymorphisms in exons 2, 3, 4, 5, 7, 8, and 9 of the PRDM16 gene were detected by PCR-SSCP, DNA sequencing and CRS-PCR-RFLP methods in 1031 cattle of the Chinese breeds: Jiaxian, Nanyang, Qinchuan, and Chinese Holstein. Three mutations (NC&#95;007314.3: g.577 G>T, 614 T>C, 212237 T>C) were detected. Animals with the homozygote genotype had lower body weight and average daily gain than those with the other genotypes. PRDM16 gene-specific SNPs may be useful markers for growth traits for marker-assisted selection programs.

Objective: To analyze the differences in the immediate effect of acupuncture on cervical spondylosis of vertebral artery type among three factors: needling technique, acupoint selection and time of needle retaining so as to option the best therapeutic program., Methods: Thirty-two cases were observed and randomly divided into 8 groups, 4 cases in each one. The orthogonal design of three factors and two levels was adopted. There were needling technique (electroacupuncture, reinforcing and reducing method), acupoint selection [C4-C7 Jiaji (EX-B 2) and three needles of neck: Tianzhu (BL 10), Jingbailao (EX-LHN 15), Dazhu (BL 11)] and time of needle retaining (5 min, 15 min). L8 (2(7)) orthogonal design table was arranged in the trial. The changes in mean velocity (Vm) of vertebral artery (VA) and basilar artery (BA) were observed before and after acupuncture., Results: The immediate effect of VA-BA blood flow was the most significant after electroacupuncture at C4-C7 Jiaji (EX-B 2), with continuous wave for 5 min. This method and acupoint selection greatly influenced the therapeutic results (both P<0.05)., Conclusion: The optimized therapeutic program of the immediate effect of acupuncture for cervical spondylosis of vertebral artery type is electroacupuncture + C4-C7 Jiaji (EX-B 2) + 5 min. The importance of different factors for the immediate effect in acupuncture treatment of cervical spondylosis of vertebral artery type is: acupoint selection > needling technique > time of needle retaining.

Objective: To observe the effect of different strength of acupuncture stimulation on blood pressure and plasma endothelin (E)-1 in spontaneous hypertension rats (SHR) ,so as to seek a better acupuncture parameter for clinical treatment of hypertension., Methods: Twenty-eight 9-week-old SHRs were randomized into mild-stimulation group, moderate-stimulation group, strong-stimulation group and model group (n = 7 in each group). Seven normotensive SD rats served as a normal control group. Acupuncture stimulation with mild, moderate and strong stimulation was applied to bilateral "Taichong" (LR 3) for 5 min, once daily for 7 days. Blood pressure (BP) was determined by using a non-invasive BP-6 detection system. Plasma ET-1 was assayed by radioimmunoassay., Results: Compared with the model group, the systolic pressure of the moderate-stimulation group on the 6th and 7th day was decreased significantly after acupuncture of "Taichong" (LR 3) (P<0. 01), being significantly lower than that of the mild- and strong-stimulation groups (P<0. 01). In comparison with the normal control group, plasma ET-1 level in the model group was increased significantly (P<0.01), while compared with the model group, only that in the moderate-stimulation group was down-regulated considerably (P<0. 01). No significant differences were found between the mild-stimulation and model groups, between the strong-stimulation and model groups, and between the mild-stimulation and strong-stimulation groups in plasma ET-1 level (P>0. 05)., Conclusion: Moderate-stimulation of "Taichong" (LR 3) can lower blood pressure and plasma EA-1 level in spontaneous hypertension rats. The reduced level of plasma ET-1 may be one of its mechanisms underlying improving hypertension.

Objective: To compare the therapeutic effects of insomnia accompanied with depressive disorders treated by acupuncture of relieving depression and regulating mind and oral administration of Trazodone., Methods: Sixty-five cases were randomly divided into a acupuncture group (33 cases) and western medication group (32 cases). In acupuncture group, Shenmen (HT 7), Baihui (CV 20), Hegu (LI 4) and Taichong (LR 3) were selected. In western medication group, Trazodone was applied with oral administration for 4 weeks. The curative effect comparison was carried on by Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Side Effect Rating Scale (SERS) of Asberg., Results: The cured and markedly effective rate of 72.7% (24/33)in acupuncture group was superior to that of 46.8% (15/32) in western medication group; after treatment, the scores of all items and the total cumulative scores of PSQI and SDS of both groups were reduced (P < 0.01, P < 0.05), of which, the sleep quality and daytime function evaluation in acupuncture group reduced more obviously than those in western medication group (both P < 0.05); the SERS scores of Asberg in western medication group were higher than those in acupuncture group., Conclusion: Acupuncture treatment of relieving depression and regulating mind is superior to Trazodone with oral administration for sleep quality and daytime function, with milder adverse reactions.

This essay studies the phenomenon of 'obtaining of qi' in acupuncture. Combined with clinical practice, the authors think that it was a habitual misunderstanding in the past to equate 'needling sensation' to 'obtaining of qi' in acupuncture practice. The two concepts are different and are related with each other. The authors have also classified the phenomenon of 'obtaining of qi' according to its depth in the skin layer. Based on the research achievements in neuroscience, the authors propose the study on 'catching' the specific cerebrations, so as to reveal the essence of 'obtaining of qi'.

Background: Due to the quick rhythm of life and work pressure, more and more people suffer from sleep quality problems. In this study, we investigated the effect of electroacupuncture on sleep quality of chronic insomniacs and the safety of electroacupuncture therapy., Methods: Four courses of electroacupuncture treatment were applied to 47 patients. With pre-treatment and post-treatment self-control statistical method, Pittsburgh sleep quality index (PSQI) scores were used for evaluating sleep quality. Polysomnogram was used for detecting insomniacs' changes in sleep architecture. The safety of electroacupuncture was evaluated by monitoring the self-designed adverse events and side effects during treatment and post-treatment., Results: Electroacupuncture considerably improved insomniacs' sleep quality and social function during the daytime. Electroacupuncture had certain repairing effect on the disruption in sleep architecture. At the same time, electroacupuncture prolonged slow wave sleep (SWS) time and relatively rapid eye movement sleep (REM sleep) time. There was no hangover, addiction or decrements in vigilance during the daytime (incidence rate was 0). However, insomnia rebound rate was about 23% within one month., Conclusions: These results suggest that electroacupuncture has beneficial effect on sleep quality improvement in the patients with chronic insomnia, which may be associated with repairing sleep architecture, reconstructing sleep continuity, as well as prolonging SWS time and REM sleep time. Electroacupuncture treatment for chronic insomnia is safe. Therefore, electroacupuncture therapy could be a promising avenue of treatment for chronic insomnia.

Objective: To observe the effect of electroacupuncture (EA) of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" on learning-memory ability and pathological changes of cerebral minute blood vessels and hippocampal structure in hypertension-hyperlipmia-vascular dementia (HH-VD) rats., Methods: Forty SD rats were randomly divided into sham-operation (sham) group (n=8), EA-I group [n=8, EA of "Baihui" (GV 20), "Dazhui" (GV 14), "Pishu" (BL 20) and "Shenshu" (BL 23), 80 Hz, 1 mA, 20 min/day, 15 days], EA-II group (n=8, EA of nonpoints, 5 mm lateral to the abovementioned acupoints), medication group (n=8, intragastric perfusion of Nimotong, 0.6 mg/mL, 20 mL/kg, 15 days), model group (n=8). HH-VD model was established by feeding the rat with high fat forage and by occlusion of the left renal artery and carotid artery. The animals' learning-memory ability was detected by Y-maze test, the synaptic structure of the hippocampal CA 1 region, and the pathological change of the cerebral cortex were observed by electronic microscope and light microscope, respectively., Results: After modeling, the blood pressure, serum total cholesterol and triglyceride (TG) levels, and the error number (EN), total reaction time (TRT) and standard number (SN, number of paw-electric-stroke for reaching correct reactions) of Y maze test increased significantly in comparison with sham group (P<0.05). After EA, the EN, TRT and SN of EA-I , EA-II and medication groups decreased significantly in comparison with model group (P<0.01), suggesting a striking improvement of the learning-memory ability after the treatment, and the EN, TRT and SN of EA-I group and medication group were significantly lower than those of EA-II group (P<0.05). Under electronic microscope, the number of synapses in hippocampal CA 1 area of HH-VD model rats reduced obviously, its postsynaptic density (PSD) was lighter, and the synaptic vesicles were fewer. Whereas in comparison with EA-II and medication groups, the synaptic number and density in EA-I group were more and bigger, and the width, length and color of PSD increased clearly. The synaptic number of EA-II group was relatively smaller compared with the other two treatment groups. Under light microscope, the vascular walls of the cerebral minute and small arteries of model group were obviously thickened and their lumina narrowed. While in EA-I group, these pathological changes were mild. In medication group the thickening of vascular walls of partial cerebral minute and small arteries were also seen., Conclusion: EA of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" can improve pathological changes of the synaptic structure of hippocampal CA 1 region and the vascular walls of cerebral minute and small arteries, which may contribute to its function in improving the learning-memory ability in HH-VD rats.

Human CYP2C8 is a key member of the CYP2C family and metabolizes more than 60 clinical drugs. A number of active site residues in CYP2C8 have been identified based on homology modeling and site-directed mutagenesis studies. In the structure of CYP2C8, the large active site cavity exhibits a trifurcated topology that approximates a T or Y shape, which is consistent with the finding that CYP2C8 can efficiently oxidize relatively large substrates such as paclitaxel and cerivastatin. The active site cavity of CYP2C8 contains at least 48 amino acid residues and many of them are important for substrate binding. The structures of CYP2C8 in complex with distinct ligands have revealed that the enzyme can bind divergent substrates and inhibitors without extensive conformational changes. CYP2C8 is a major catalyst in the metabolism of paclitaxel, amodiaquine, troglitazone, amiodarone, verapamil and ibuprofen, with a secondary role in the biotransformation of cerivastatin and fluvastatin. CYP2C8 also metabolises endogenous compounds such as retinoids and arachidonic acid. Many drugs are inhibitors of CYP2C8 and inhibition of this enzyme may result in clinical drug interactions. The pregnane X receptor, constitutive androstane receptor, and glucocorticoid receptor are likely to involve the regulation of CYP2C8. A number of genetic mutations in the CYP2C8 gene have been identified in humans and some of them have functional impact on the clearance of drugs. Further studies are needed to delineate the role of CYP2C8 in drug development and clinical practice.

Objective: To optimize the technological parameters of the extraction and purification process of total ginsenosides from Radix Ginseng., Methods: With the contents of ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1, the orthogonal design was adopted to optimize the extraction process. The purification process was studied by optimizing the elutive ratio of total ginsenosides as the marker. HPLC and spectrophotometer were employed for the study., Results: The optimum conditions were as follows:Using 8 times volume of 75% ethanol extracting for 120 minutes and 2 times, the extraction temperature was 85 degrees C. AB-8 macroporous resin was selected, and the eluant was 4 BV 70% ethanol., Conclusion: The optimal conditions of extracting and purifying the total ginsenosides from Radix Ginseng is feasible.

Visfatin is a protein that is preferentially produced in visceral adipose tissue. Both its tissue expression and secreted plasma levels increase in parallel with obesity. Therefore, the present study is focused on detecting insertion in bovine visfatin gene and analyzing its effect on growth traits in four Chinese cattle breeds (Nangyang, Qinchuan, Jiaxian, and Chinese Holstein) using PCR-SSCP, DNA sequencing and agarose electrophoresis methods. For the first time, a 35-bp insertion was described in the gene and two alleles were revealed: Wand I. The chi2-test analysis demonstrated that all breeds were in agreement with Hardy-Weinberg equilibrium (P > 0.05). The associations of the novel 35bp-insertion of visfatin gene with growth traits of Nanyang cattle at 6, 12, 18, and 24 months old were analyzed: 6-month-old cows with genotype WW had greater birth weight than cows with genotype II and WI (P < 0.01 or P < 0.05). These results suggest that the presence of 35bp-insertion in visfatin gene may influence the birth weight and bodyweight in 6-month-old cows.

Objective: To observe the cerebral activating effects of needling at Waiguan (SJ5) versus SJ5 plus Yanglingquan (GB34) points in young healthy volunteers based on the hypothesis of "needling effect of combined acupuncture points relates to the brain activation"., Methods: Sixteen healthy volunteers were randomly divided into SJ5 group and SJ5 plus GB34 group, and there were 8 volunteers in each group. The volunteers in the two groups received needling at corresponding points on the right hand or foot respectively. Nuclear magnetic resonance (1.5T, GE Corporation) was used for functional magnetic resonance imaging (fMRI) of the brain before and during the needling, and the obtained experimental data in the regional brain were processed and analyzed by the method of region of interest (ROI)., Results: The ROI activation induced by needling of SJ5 or SJ5 plus GB34 was all relatively concentrated (activation rate more than 4 or activation point more than 10) on bilateral frontal and parietal lobes. There were no significant differences in ROI activation rates of brain regions between the two groups. ROI activation points showed that needling at SJ5 could activate the right cerebellum specifically (P < 0.05, vs SJ5 plus GB34), while needling at SJ5 plus GB34 could activate the left parietal and occipital lobes and bilateral basal ganglion more effectively than activate the other brain regions (P < 0.05, vs SJ5). ROI activation strength showed that needling at SJ5 plus GB34 could more strongly activate the right cerebellum (P < 0.05, vs SJ5)., Conclusion: Based on fMRI data, a kind of acupuncture point combination of SJ5 and GB34 within the hand-foot Shaoyang meridians, could improve the motor and sensory dysfunctions and equilibrium disturbance. The effect of combined acupuncture points was proved by cerebral activity initially.

CYP2D6 accounts for only a small percentage of total hepatic CYPs (<2%), but it metabolizes approximately 25% of clinically used drugs (>100) with significant polymorphisms. A number of drugs acting on the central nervous system and cardiovascular system are substantially metabolized by CYP2D6. The enzyme also utilizes hydroxytryptamines and neurosteroids as endogenous substrates. In addition, CYP2D6 metabolizes procarcinogens and neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and indolealkylamines. Typical CYP2D6 substrates are usually lipophilic bases with a planar hydrophobic aromatic ring and a nitrogen atom which can be protonated at physiological pH, but several atypical substrates such as spirosulfonamide and pactimibe do not contain a basic nitrogen atom. The structure of human CYP2D6 has been recently determined and shows the characteristic CYP fold as observed in other members of the CYP superfamily, with a well-defined active site cavity above the heme group with a volume of approximately 540 A(3). CYP2D6 is largely uninducible by prototypical CYP inducers such as phenobarbital, rifampin and dexamethasone, but it is regulated by hepatocyte nuclear factor-4alpha, a nuclear receptor. CYP2D6 is subject to inhibition by a number of drugs and this may provide an explanation for numerous clinical drug interactions. CYP2D6 has an important role in drug development and it is a common practice for pharmaceutical industry nowadays to a great extent screen drug candidates early in development as possible CYP2D6 substrates and/or inhibitors and drop such candidates where they have alternatives. This candidate selection might eventually lead to a less prominent role of this enzyme in the future for drug metabolism and less interindividual variability in drug exposure and minimize potentially adverse drug interactions. Further studies are warranted to delineate the molecular mechanisms involved in the function and regulation of CYP2D6.

In the present paper, the authors introduce the development of researches on the specificity of acupoints in morphological structure (nerves, blood vessels, musculotendons, connective tissues, etc), biophysical characteristics (electricity, sonics, photology, thermology, electromagnetism), pathological response, and effectiveness. However, the aforementioned researches are basically at the stage of phenomenon-observation, some key factors influencing acupoint specificity and the underlying mechanisms have no definite or lack convincing results. Further studies should aim at those acupoints for some effective diseases (or symptoms) of acupuncture by using multiple modern scientific techniques. Some key scientific issues about the biophysical characteristics, pathological responses, efficacy, and combination regularity of acupoints should be solved reasonably. Moreover, theoretical models about acupoint specificity should be established for developing the theory of acupoint learning.

Objective: To observe the effect of electroacupuncture (EA) on learning-memory ability of vascular dementia (VD) rats, and the simultaneous changes of plasma and cerebral somatostatin (SS) and beta-endorphin (EP) contents., Methods: Forty-one SD rats were randomly divided into control (n=8), model A (n=8, no treatment) and B (n=8, intragastric perfusion of 15% saline), EA (n=9) and medication (n=8, intragastric perfusion of Nimoldipine, 12 mg/kg) groups. VD model was established by using modified 4-vessels occlusion method. EA (150 Hz, 1-2 mA) was applied to "Baihui" (GV 20), "Dazhui" (DU 14), "Pishu" (BL 20) and "Shenshu" (BL 23) for 20 min, once daily for 15 days. Morris water maze tests were conducted for evaluating the rats' learning-memory ability. The contents of SS and beta-EP in plasma and brain tissue were measured by radioimmunoassay (RIA)., Results: In comparison with sham-operation group, the escape latency (EL) prolonged significantly and the target-platform crossing times decreased remarkably (P<0.01) in model group B. In comparison with model group B, EL shortened and target-platform crossing times increased both significantly in EA and medication groups (P<0.01). Plasma and cerebral SS, and cerebral beta-EP contents of model groups A and B were significantly lower than those of sham-operation group(P<0.01), while plasma beta-EP level had no obvious change (P>0.05). Plasma and cerebral SS, and cerebral beta-EP contents in both EA and medication groups were considerably higher than those in model groups A and B (P<0.01). No significant differences were found between EA and medication groups in EL, target-platform crossing times, plasma and cerebral SS and beta-EP levels, and between model group A and model group B in plasma and cerebral SS and beta-EP levels (P>0.05)., Conclusion: EA can raise plasma and cerebral SS and cerebral beta-EP levels, and improve the learning-memory ability in VD rats.

"Acupoints-brain relation hypothesis" is put forward according to the combination of cerebral functional imaging techniques, positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), and the studies of the essence of acupoints. Analysis based on the living state of human being, the cerebral function and the objective images and data will result in: (1) a model of cerebral functional imaging for the definition of acupoints, any points that coincide the basic factors of the model can be definited as an acupoint; (2) a model of cerebral functional imaging for needling sensation, any cerebral functional changes caused by needling coincide the basic factors of the model can be definited as needling sensation; (3) a study on characteristics and regular patterns of association of the acupoints selected along channels.

Objective: Using methods of clinical scale assessment and cerebral functional imaging to compare the relative specificity of needling acupoints Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) in intervening vascular dementia (VD) in different areas in the brain., Methods: Fifty patients with VD were randomized into 5 groups. Needling on conventionally used acupoints of hand and foot three Yang-meridians aiming at hemiplegia was applied to the patients in Group A, and needling on DU20 to Group B, on DU26 to Group C, on HT7 to Group D and on all the three to Group E was applied additionally. Assessments of Mini Mental State Examination (MMSE), Activities of Daily Living (ADL) and Family Attitude Questionnaire (FAQ) were made. And the positron emission computerized tomography (PET) and single photon emission computerized tomography (SPECT) examinations were conducted in 5 selected patients from each group before and after treatment., Results: Needling on conventional acupoints plus DU20 could effect the inner temporal system, thalamencephalon system and prefrontal cortical system to improve memory and executive capacity of VD patients; conventional acupoints plus DU26 could effect more to the prefrontal cortical system to obviously elevate the executive capacity; that plus HT7 would reveal an effect similar to but rather weaker than plus DU20, and effect more to memory; and that plus all the three simultaneously could effect rather roundly multiple aspects of the nervous system related to intellectual activities, to elevate the recognition and enhance the executive capacity., Conclusion: Needling on various acupoints like DU20, DU26 and HT7 have effects on different brain areas.

Objective: To explore the underlying neuroimmunological mechanism of electroacupuncture (EA) in the treatment of perennial allergic rhinitis (PAR)., Methods: One hundred PAR outpatients were evenly randomized into EA group and medication group. Patients in EA group were treated with EA (5-10 mA, 80-100 Hz, and 30 min of stimulation) of Sphenopalatine ganglion area, Yingxiang (LI 20), Shangyingxiang (EX-HN 8), Yintang (EX-HN 3), supplemented with other acupoints according to syndrome-differentiation (once daily, 10 days being a therapeutic course). Patients of medication group were treated by Cetirizine (10 mg/times, t. i.d, peros). Before and after the treatment, blood samples of the ulnar vein were collected for detecting plasma vasoactive intestinal peptide (VIP) and substance P (SP) contents with radioimmunoassay., Results: After the treatment, of the two 50 cases in EA and medication groups, 20 (40%) and 16 (32%) had an obvious improvement, 28 (56%) and 24 (48%) had an improvement, 2 (4%) and 10 (20%) failed, with the total effective rates being 96% and 80% separately. The therapeutic effect of EA group was significantly superior to that of medication group (P < 0.05). Self-comparison of each group showed that after the treatment, both plasma VIP and SP levels of two groups lowered apparently (P < 0.05, 0.01). Comparison between two groups showed that after the treatment, the content of VIP in EA group was markedly lower than that of medication group, while no significant difference was found between two groups in plasma SP levels (P > 0.05)., Conclusion: EA can effectively relieve perennial allergic rhinitis patients' clinical symptoms, which is closely related to its functions in lowering plasma VIP and SP levels.

Objective: To observe the relationship between changes of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) contents in the hippocampus and learning-memory ability in vascular dementia (VD) rats and the interventional effect of electroacupuncture (EA) on the contents of IL-1beta and TNF-alpha., Methods: SD rats were randomized into control group (n = 10), model group (n = 11) and EA group (n = 12). VD model was established by using Pulsinelli's 4-vessel occlusion (4-VO) technique. EA (2 mA, 50 Hz) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) for 20 min, once a day and continuously for 15 days. The rats' learning-memory abilities were tested by Morris water-maze (place navigation test and special probe test) continuously for 6 days, and then the rats were sacrificed for taking hippocampus tissue which was homogenized for detecting IL-1beta and TNF-alpha contents by using radioimmunoassay (RIA) technique., Results: Place navigation test and special probe test showed that compared with control group, the mean escape latencies and the times of crossing the original platform quadrant in model group and EA group were significantly longer and more (P < 0.01). Comparison between model group and EA group indicated that the escape latency of the later group was markedly shorter than that of the former group (P < 0.05), no significant differences were found between EA group and control group in the staying duration in the original platform quadrant (P > 0.05), suggesting an improvement of learning-memory abilities after EA. In comparison with control group, both IL-1beta and TNF-alpha contents in the hippocampus tissue were significantly higher in model group and EA group (P < 0.05, 0.01), and those of EA group were considerably lower than those of model group (P < 0.01)., Conclusion: EA can improve VD rats' learning-memory abilities, which is closely associated with its effects in suppressing VD-induced increase of IL-1beta and TNF-alpha levels in the hippocampus.

Objective: To study the effects of electro-acupuncture (EA) on electroencephalography (EEG) in vascular dementia (VD) patients., Methods: According to the Hasegawa dementia scale (HDS), the severity of 46 VD patients were classified into three grades as gentle, medium and severe, in the same time, they were divided into the EA group (n = 23) and the nimotop group (n = 23) randomly. Changes of EEG in the patients were observed before and after treatment., Results: The degree of normality of EEG in VD patients were positively correlated with the severity of their illness, i. e. the severer VD, the more obvious the abnormal EEG changes., Conclusion: EEG can be accessible for evaluating the severity of VD, and the electrical activity of brain in VD patients could be improved by EA therapy.

Objective: To probe into regularity of effects of electroacupuncture on focal cerebral infarction., Methods: Focal cerebral ischemia model was established by middle cerebral artery heat-occlusion (MACO) method. Electroacupuncture was given at Dazhui (GV 14) and Baihui (GV 20). NSS was used for evaluation of neurological impairment, TTC staining method for detection of the infarct volume, and HE staining method for investigation of the pathomorphologic lesion of the brain., Results: MCAO could induce neurologic impairment, cerebral infarction and cerebral pathological lesion in the rat, all of these changes could be cured spontaneously in varying degrees with prolongation of ischemic time, but electroacupuncture could relieve the lesions to a certain extents., Conclusion: Electroacupuncture can improve neurologic deficit impairment, reduce the volume of cerebral infarction and ischemic pathological lesion, early interfere of acupuncture and moxibustion is of very important clinical significance for treatment of ischemic apoplexy.

Objective: To observe the effect of needling in Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) on glucose metabolism in the lentiform nucleus in patients with vascular dementia., Methods: Ten patients with vascular dementia were randomized equally into control group to receive the treatment of needling in the routine acupoints for hemiplegia (chosen from 6 Yang meridians of hand and foot) and treatment group with needling in 3 additional acupoints of Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) for dementia. All the patients were examined by positron emission tomography (PET) to detect glucose metabolism in the bilateral lentiform nuclei before and after treatment., Results: Glucose metabolism in the lentiform nucleus in normal lateral brain was obviously enhanced in the treatment group, but not in the bilateral lentiform nuclei in the control group after treatment., Conclusion: The effect of needling in Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) for treatment of vascular dementia may involve the enhancement of glucose metabolism in the lentiform nucleus.

Objective: To study the relative specialty of the acupoints of Baihui (DU20), Shuigou (DU26) and Shenmen (HT7) in treating vascular dementia (VD)., Methods: Fifty patients suffering from VD were divided into 5 groups randomly and treated by conventional acupuncture for hemiplegia, or conventional acupuncture plus needling in DU20, DU26, HT7 respectively or simultaneously. Clinical symptoms were observed, and the scales such as Hasegawa's dementia scale-recension (HDS-R), activities of daily living (ADL) and functional activities questionnaire (FAQ) were used for assessment before and after acupuncture treatment. The scores were processed statistically., Results: DU20 and HT7 could improve the abilities of memory, orientation, reaction and reduce adamancy and trance. Besides, DU 20 was helpful in improving the abilities of understanding, calculating and social adapting. While DU26 is helpful in treating retardation, failure in daily activities, trance and poor memory. The combination of the 3 acupoints could improve the intelligence and social adapting ability of VD patients., Conclusion: DU20, DU26 and HT7 had its own effect in treating VD, but the effect of three points used in combination was the best.

Objective: To compare the relative characteristics of Baihui (GV 20), Shuigou (GV 26) and Shenmen (HT 7) in treatment of vascular dementia., Methods: Fifty cases of vascular dementia (VD) were divided into 5 groups randomly. The patients in the group A were treated by acupuncture at routine acupoints. Besides the routine acupoints of the group A, Baihui (GV 20), Shuigou (GV 26) and Shenmen (HT 7) were added to treat the patients in group B, C, D, respectively, while Baihui, Shuigou and Shenmen were added to the group E. The clinical symptoms and signs were observed., Results: Baihui and Shenmen can improve memory, orientation, reaction, obstinacy and trance of VD patients. Baihui is good at helping the patients to understand, calculate and adapt the society. Shuigou is good at improvement of sleeping, slow reaction, trance and memory of the patients. The combination of Baihui, Shuigou and Shenmen can generally promote intelligence level and society adaptive ability., Conclusion: Baihui, Shuigou and Shenmen have own characteristics in improving clinical signs and intelligence of patients of VD, and the combination of the 3 acupoints has the best effect in treating VD.

Objective: To find a clinically effective therapy for apoplectic pseudobulbar palsy., Methods: Seventy-five cases of apoplectic pseudobulbar palsy were randomly divided into 3 groups, acupuncture group, western medicine group and acupuncture plus medicine group. They were treated for one month., Results: The scores for clinical symptoms and signs, and the clinical scores for water provocative test in the acupuncture plus medicine group and the acupuncture group were superior to that in the western medicine group with significant difference (P < 0.01), and the therapeutic effects of the 3 groups were related with age, course of disease and condition of illness., Conclusion: Acupuncture has some predominances in treatment of apoplectic pseudobulbar palsy.

Objective: To study the effect of electro-acupuncture (EA) in regulating calcium (Ca2+) content in brain neurocytes of rats with focal cerebral ischemia., Methods: The changes of Ca2+ content in ischemic neurocytes were observed by using laser confocal scanning microscope., Results: Ca2+ content did not change significantly in cerebral cortex when the brain ischemia occurred for 1 hr, but it raised significantly in striatum neurocytes. Both the Ca2+ contents in striatum and cortex area increased significantly 3 hrs after ischemia occurrence and the content in striatum was higher than that in cortex significantly. Brain Ca2+ content could be reduced significantly after the 3 hrs ischemic brain were treated by EA for 30 min., Conclusion: EA could regulate the content of Ca2+ in the ischemic area of brain, inhibit Ca2+ overload, so as to protect neurons from ischemic injury.

The authors describe digital processing of mammographic images based on simulation of the procedure performed by radiologists to analyse radiographs. Image processing allows automatically enhancing contrasts and expressing them as a range of different light intensities and colors. Minimum contrast differences that are difficult to perceive with the bare eye are thus highly enhanced. This processing of mammographic images has proved useful not only to detect discrete lesions, but also to differentiate benign and malignant lesions.