Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PURPOSE: To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. RESULTS: The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. CONCLUSION: Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction.

Protective effects of ginsenoside Rb1 on septic rats and its mechanism.

This study aims to observe the protective effects of ginsenoside Rb1 on liver and lung in rats with septic shock and reveal its mechanism. Rats were randomly divided into three groups: sham, cecal ligation and puncture (CLP), and CLP with ginsenoside Rb1. Then, the survival rate, arterial blood pressure, TLR4 mRNA, and TNF-α levels were determined. The liver and lung tissues were stained with hematoxylin-eosin (HE). The overall survival rate of the Rb1 group was significantly higher than that of the CLP group. Mean arterial blood pressure went down in both the CLP and Rb1 groups after CLP, and there was a significant difference both in the sham and Rb1 groups when compared with the CLP group. The Rb1 treatment group had markedly lower TLR4 mRNA expression and TNF-α levels than the CLP group. In the CLP group, pathology showed swelling, degeneration, necrosis, and neutrophil infiltration in the liver and alveolar epithelial cells. However, in the Rb1 group, there was mild degeneration and slight neutrophil infiltration, but no obvious necrosis. Rb1 may improve the survival rate, ameliorate arterial blood pressure, and protect the liver and lung in septic shock rats by downregulating the expression of TLR4 mRNA and inhibiting the production of TNF-α.

Phospholamban antisense RNA improves SR Ca2+-ATPase activity and left ventricular function in STZ-induced diabetic rats.

OBJECTIVE: To study the effect of phospholamban antisense RNA (asPLB) on sarcoplasmic reticulum Ca2+-ATPase activity and cardiac function in rats with diabetes mellitus (DM) mediated by recombinant adeno-associated virus (rAAV) vector. METHODS: Six weeks after the induction of DM by streptozotocin injected intraperitoneally, the rats were divided into three groups, namely: DM-rAAV-asPLB group, DM-saline group and DM group (control group). The rats in the DM-rAAV-asPLB group were intramyocardially injected with rAAV-asPLB, the rats in the DM-saline group were injected with saline, and those in the control group did not receive any treatment. Six weeks after gene transfer, the expressions of PLB protein and PLB phosphorylation were detected by Western-blot, while the activity of sarcoplasmic reticulum (SR) Ca2+-ATPase and left ventricular function were measured. RESULTS: The PLB protein expression level was significantly higher whereas the PLB phosphorylation, SR Ca2+-ATPase activity and left ventricular function were significantly lower in the DM-saline group than in the control group. No significant difference was found in PLB protein expression level, PLB phosphorylation or SR Ca2+-ATPase activity between the DM-rAAV-asPLB group and the control group. The left ventricular function in the DM-rAAV-asPLB group was poorer than in the control group and was better than in the DM-saline group. CONCLUSION: rAAV-asPLB can down-regulate PLB protein expression and up-regulate PLB phosphorylation and SR Ca2+-ATPase activity, thus contributing to the improvement of in vivo left ventricular function.

[Effects of adrenergic beta-1 antagonists on hemodynamics of severe septic patients].

OBJECTIVE: To explore the effects of adrenergic beta-1 antagonists on hemodynamics of severe septic patients. METHODS: A total of 16 severe septic patients underwent mechanical ventilation from June 2012 to December 2012 at Fourth Affiliated Hospital of Nanchang University. There were 14 males and 2 females with a mean age of (58 ± 6) years (range: 48 - 67 years). Among them, there were multiple trauma (n = 4), acute severe pancreatitis (n = 6) and recent tumorectomy for gastrointestinal cancer (n = 6). The adrenergic beta-1 antagonist esmolol was injected through central venous catheter to reduce heart rate by 20% from baseline. Various indices (heart rate, systolic blood pressure, diastolic blood pressure, cardiac output, cardiac index, central venous pressure, pulmonary artery wedge pressure, pulmonary vascular resistance index, systemic vascular resistance index and stroke volume index) were monitored by a multifunctional and hemodynamic monitor connected to pulmonary artery catheter. And other indices of arterial pressure of carbon dioxide (PaCO2), lactate (Lac) concentration, superior vena cava oxygen saturation (ScvO2), superior vena cava carbon dioxide pressure (PcvO2) and central venous-to-arterial carbon dioxide tension difference (Pcv-aCO2) were measured by a blood-gas-analyzer before 10 minutes and after 3 hours of dosing. RESULTS: Heart rate and cardiac index decreased significantly at 3 hours post-dosing compared with that at pre-dosing ((91 ± 13) vs (114 ± 15) beats per minute, (3.4 ± 0.7) vs (4.2 ± 0.8) L×min(-1)×m(-2), P < 0.05), but systolic blood pressure, diastolic blood pressure, central venous pressure, pulmonary wedge pressure, pulmonary vascular resistance index, systemic vascular resistance index and stroke index showed no significant changes ((100 ± 13) vs (108 ± 14) mm Hg (1 mm Hg = 0.133 kPa), (62 ± 7) vs (64 ± 6) mm Hg, (11.8 ± 2.5) vs (12.1 ± 2.4) mm Hg, (13 ± 5) vs (14 ± 4) mm Hg, (201 ± 72) vs (179 ± 95) dyn×s/(cm(5)×m(2)), (1360 ± 520) vs (1366 ± 538) dyn×s/(cm(5)×m(2)), (40 ± 9) vs (38 ± 6) ml/(beat×m(2)), all P > 0.05). ScvO2, Lac and Pcv-aCO2 also showed no significant change ((72.8 ± 5.3)% vs (70.1 ± 4.0)%, (2.11 ± 0.13) vs (2.31 ± 0.23) mmol/L, (3.9 ± 1.0) vs (4.5 ± 0.8) mm Hg, all P > 0.05). CONCLUSION: Adrenergic beta-1 antagonist may reduce cardiac output in proportion to the percentage decreases in heart rate in severe septic patients without adverse effects upon cardiac function and systemic perfusion.

[Progress of experimental researches on acupuncture intervention for Alzheimer's disease based on SAMP8 mice model].

Alzheimer's disease (AD), also called senile dementia, is a neurodegenerative disease, characterized by progressive memory and cognitive impairment and different degrees of behavior-mental dysfunction. Clinical trials displayed that acupuncture therapy is effective in relieving symptoms of AD patients. In recent years, many experimental studies have been conducted in SAMP8 mice to explore the underlying mechanisms of acupuncture in improving AD. Results showed that acupuncture therapy can intervene the central pathological process of AD in multiple approaches, including reducing formation of cerebral ß amyloid protein and promoting its removal, intervening the phosphorylation process of Tau protein, improving mitochondrial and synaptic structure, enhancing autophagy activity, accelerating cerebral blood flow, and increasing the levels of estrogen content, and improving the learning and memory ability, etc.

Mechanisms of Acupuncture in Improving Alzheimer's Disease Caused by Mitochondrial Damage.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among the elderly and it accounts for nearly 80% of all dementias. The pathogenesis of AD is complicated and enigmatic thus far. The mitochondrial cascade hypothesis assumes that mitochondrial damage may mediate, drive, or contribute to a variety of AD pathologies and may be the main factor in late-onset AD. Currently, there are no widely recognized drugs able to attenuate mitochondrial damage in AD. Notably, increasing evidence supports the efficacy of acupuncture for improving the mitochondrial structure and protecting mitochondrial functions in AD. This review reports the mechanisms by which acupuncture regulates mitochondrial dynamics, energy metabolism, calcium homeostasis and apoptosis. In conclusion, these findings suggest that AD mitochondrial dysfunction represents a reasonable therapeutic target and acupuncture could play a significant role in preventing and treating AD.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session.

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear. Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes. Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment. Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

The pro-inflammatory factors contribute to the EEG microstate abnormalities in patients with major depressive disorder.

Pro-inflammatory factors may be associated with abnormalities in functional brain networks, which may be a mechanism in the pathogenesis of major depressive disorder (MDD). Electroencephalogram (EEG) microstates reflect the functioning of brain networks. However, the relationship between pro-inflammatory factors and the microstate abnormalities in patients with MDD is poorly understood. 24 MDD patients and 24 age-and sex-matched healthy controls (HC) were recruited. Montgomery-Asberg Depression Rating Scale(MADRS) were assessed. Serum (interleukin- 2(IL- 2), tumor necrosis factor-α (TNF-α) and hs-C-reactive protein (CRP)and EEG data were collected. K-means clustering was performed to characterize different microstates. For each microstate, duration, occurrence and coverage were estimated. Four microstates (e.g. A, B, C, D) were characterized, MDD group showed lower duration, occurrence and coverage of microstate B and microstate D, while higher duration of microstate A and microstate C and levels of IL-2, TNF-α, hs-CRP than HC group. The duration, occurrence and coverage of microstate D were negatively correlated with levels of pro-inflammatory factors (IL-2, TNF- α and hs- CRP) (all P < 0.05). Serum pro-inflammatory induced the abnormalities of microstate D. Together, these findings add to the understanding of the pathophysiology of MDD and point to pro-inflammatory factors contribute to EEG microstate abnormalities in patients with MDD.

[Closed-loop neuromodulation technique brings new opportunities and challenges to acupuncture and moxibustion therapies].

In recent years, the newly appeared closed-loop neuromodulation technique composed of closed-loop controlled stimulation system and neuromodulation is the product of medicine and inter-disciplines. In medical clinical practice, the idea of closed-loop controlled stimulation can be seen everywhere. When both the patient and acupuncturist achieve the state of "Deqi" simultaneously, it is a kind of feedback adjustment process similar to that of the closed-loop stimulation system. Cross-functional multidisciplinary development is the future trend of medical science progress. The acupuncture-moxibustion discipline can draw lessons from the research experience and achievements of closed-loop neuromodulation techniques to explore the origin of the compatibility of meridians, acupoints, and needling manipulations.

Value of Magnifying Chromoendoscopy and Magnifying Optical Enhancement Technology in Classifying Colorectal Polyps: A Prospective Controlled Study.

BACKGROUND AND AIMS: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. RESULTS: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. CONCLUSION: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075.

Peripheral pulmonary nodules: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression.

BACKGROUND: The aim of this study is to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules. METHODS: Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated. RESULTS: The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05). CONCLUSION: Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice.

OBJECTIVE: To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-ß (A ß) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. RESULTS: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A ß expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. CONCLUSION: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A ß-containing aggregates.

[Protective effects of electric stimulation of vagus nerve on acute lung injury in rat with sepsis].

OBJECTIVE: To investigate the protective effect of stimulation of vagus nerve on acute lung injury in rat with sepsis. METHODS: Sepsis was reproduced by cecal ligation and puncture (CLP). Forty male Sprague-Dawley (SD) rats were randomly divided into 4 groups (each n=10): SHAM group received performed sham surgery. In CLP group, CLP was performed. In vagotomy (VGX) group, rats were subjected to bilateral cervical VGX following CLP. In vagus stimulation (STM) group, rats were subjected to bilateral cervical VGX after CLP and the efferent end of the left vagus nerve was stimulated with electric current. The animals were sacrificed at 18 hours after production. Tumor necrosis factor-alpha (TNF-alpha) level in blood was detected, arterial blood lactic acid concentration,pH, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), base excess (BE) and lung wet/drying (W/D) ratio were determined. The histopathology and ultra-microstructure of the lung were observed. RESULTS: The TNF-alpha and lactic acid concentrations, PaCO2 and W/D ratio were all increased, and pH, PaO2, BE all lowered in CLP group and VGX group compared with those of SHAM group (P<0.05 or P<0.01). Compared with CLP group, TNF-alpha, lactic acid concentration,PaCO2,W/D ratio in STM group were decreased obviously, and pH, PaO2 and BE were all increased (P<0.05 or P<0.01). The lung tissue pathology and ultra-microstructure changes indicated that lung injury was severe in CLP group than in SHAM group and was ameliorated in STM group compared with that of CLP group and VGX group. CONCLUSION: The results suggest that direct electrical stimulation of the efferent end of vagus nerve can protect lung against injury induced by sepsis in rat.

[Protective effect of the cholinergic anti-inflammatory pathway against hemorrhagic shock in rats].

OBJECTIVE: To investigate the effect of the cholinergic anti-inflammatory pathway on hemodynamics in hemorrhaged rats. METHODS: Hemorrhagic shock was induced by modified Wiggers method until mean arterial pressure (MAP) was stabilized within the range of 35 to 40 mm Hg (1 mmHg=0.133 kPa). Thirty male Sprague-Dawley rats were randomly divided into six groups: sham group, hemorrhagic shock (Hem) group, vagotomy (VGX) group, vagus stimulation (STM) group, cholinergic inhibitor (THA) group and N receptor inhibitor (alpha-BGT) group. The distal end of the left vagus nerve trunk was placed on bipolar platinum electrode connected to a stimulation module and controlled by an acquisition system. Stimuli with constant voltage (5 V, 2 ms, 1 Hz) were applied to nerve for 12 minutes, starting 5 minutes after MAP stabilized at a level of 35 to 40 mmHg. Before stimulation a blood pressure transducer was implanted in the common carotid artery for continuous registration of MAP. Blood samples and liver samples were collected from animals of all groups after stimulation. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and liver nuclear factor kappa-B (NF-KappaB) were determined. RESULTS: MAP was markedly lowered at the end of bleeding, and the levels of serum TNF-alpha and liver NF-KappaB markedly increased 45 minutes after the bleeding was discontinued. Bilateral cervical vagotomy did not significantly modify the changes in serum TNF-alpha, but slightly increased liver NF-KappaB activation. Application of constant electric current to the distal end of the vagus trunk significantly reduced serum TNF-alpha and blunted liver NF-KappaB activation. Tetrahydroamino-acridine (THA,1.5 mg/kg, intravenous drip administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNF-alpha and liver NF-KappaB amounts, but alpha-bungarotoxin (1.0 microg/kg intravenous drip) pretreatment reverted the inhibitory effects of vagal stimulation. CONCLUSION: The result suggest that direct electrical stimulation of the vagus nerve and its transmitter can significantly attenuate peak serum TNF-alpha amounts, inhibit the expression of liver NF-KappaB, and prevent the development of hypotension, thus it might produce a potential protective effect on hemorrhaged rats through acetylcholine (Ach) binds NAch receptor alpha 7 subunit which exists in the macrophage.

[Protective effect of ketamine against septic shock in rats].

OBJECTIVE: To investigate the effects and the mechanism of ketamine on hemodynamics and pro-inflammatory cytokine levels of plasma in septic shock rats. METHODS: Cecal ligation and puncture (CLP) was used to reproduce septic shock model. Twenty healthy and male Sprague-Dawlay (SD) rats weighing (225+/-25) g were randomly divided into four equal groups: Sham CLP group, CLP group, ketamine I (KT I) and ketamine II (KT II) group. Thirty minutes before CLP, normal saline (0.9 %) was infused continuously at a rate of 5 ml.kg(-1).h(-1) through the left femoral vein cannula in sham CLP and CLP group, and ketamine (5 mg.kg(-1).h(-1) and 10 mg.kg(-1).h(-1), respectively) was infused continuously in KT I or KT II group. The right femoral artery was cannulated to monitor mean arterial pressure. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays (ELISA). RESULTS: CLP produced progressive hypotension, and a large increase in the plasma TNF-alpha and IL-6 concentrations. The hemodynamic responses were reversed and the cytokine responses were suppressed in ketamine treated animals. CONCLUSION: Ketamine administration has protective effect against septic shock in CLP rats.

Use acupuncture to treat functional constipation: study protocol for a randomized controlled trial.

BACKGROUND: Whether acupuncture is effective for patients with functional constipation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using acupuncture to treat functional constipation. DESIGN: A randomized, controlled, four-arm design, large-scale trial is currently undergoing in China. Seven hundred participants are randomly assigned to three acupuncture treatment groups and Mosapride Citrate control group in a 1:1:1:1 ratio. Participants in acupuncture groups receive 16 sessions of acupuncture treatment, and are followed up for a period of 9 weeks after randomization. The acupuncture groups are: (1) Back-Shu and Front-Mu acupoints of Large Intestine meridians (Shu-Mu points group); (2) He-Sea and Lower He-Sea acupoints of Large Intestine meridians (He points group); (3) Combining used Back-Shu, Front-Mu, He-Sea, and Lower He-Sea acupoints of Large Intestine meridians (Shu-Mu-He points group). The control group is Mosapride Citrate group. The primary outcome is frequency of defecation per week at the fourth week after randomization. The secondary outcomes include Bristol stool scale, the extent of difficulty during defecating, MOS 36-item Short Form health survey (SF-36), Self-Rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The first two of second outcomes are measured 1 week before randomization and 2, 4, and 8 weeks after randomization. Other second outcomes are measured 1 week before randomization and 2 and 4 weeks after randomization, but SF-36 is measured at randomization and 4 weeks after randomization. DISCUSSION: The result of this trial (which will be available in 2012) will confirm whether acupuncture is effective to treat functional constipation and whether traditional acupuncture theories play an important role in it. TRIALS REGISTRATION: Clinical Trials.gov NCT01411501.

[Effect of electroacupuncture of "Baihui" (GV 20)-"Yintang" (EX-HN 3) on the expression of glucocorticoid and glucocorticoid receptor mRNA of the chronic stress model rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of glucocorticoid (GC) mRNA and GC in the hippocampus, hypothalamus and pituitary in depression rats so as to study its mechanism underlying EA-resisting depression. METHODS: Seventy SD rats were randomized into normal control, model, Fluoxetine (Flu), constraint-stress, EA, RU 486 (an antagonist of GC) and EA+ RU 486 groups (n = 10/group). Chronic depression model was established by lonely raising and chronic unpredictable mild stress for 21 days. EA (2 Hz, 0.6 mA) was applied to "Baihui" (GV 20) and "Yintang" (EX-HN 3) for 20 min, once daily for 21 days. Subcutaneous injection of RU 486 (20 mg/kg) was given to the rats from the 14th day on and con- tinuously for 7 days in order to block the negative feedback reflex of hypothalamus-pituitary-adrenal (HPA) axis. Cortisol (CORT) content of the adrenal gland tissue was detected by radioimmunassay. The expression of GC receptor (GR) mRNA in the hippocampus, hypothalamus and pituitary tissues was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with the normal control group, adrenal CORT content of model group was increased significantly (P < 0.05), and in comparison with model group, adrenal CORT level of EA group decreased evidently (P < 0.05). Comparison between the RU 486 and EA + RU 486 groups showed that the adrenal CORT content, and hippocampal GR mRNA expression level of the latter were remarkably lower than those of the former (P < 0.05). Compared with the normal control group, the expression level of GR mRNA of the hipppocampal and pituitary tissues in the model, constraint-stress, and RU 486 groups,and those of the hypothalamus in the constraint-stress and RU 486 groups were down-regulated significantly (P < 0.05). In comparison with the constraint-stress group, hippocampal, hypothalamic and pituitary GR mRNA expression level in the EA group were upregulated considerably (P < 0.05). No significant differences were found among model, Flu, constraint-stress, RU 486 and EA + RU 486 groups in the ardenal CORT contents, and hippocampal, hypothalamic and pituitary GR mRNA expression levels (P > 0.05). CONCLUSION: EA can effectively down-regulate adrenal CORT content and hippocampal GR mRNA expression and normalize the function of HPA axis negative feed reflex in the depression rats, which may contribute to its effect in relieving depression.

[Quality control of acupuncture clinical trials].

In order to improve the quality of acupuncture clinical trials, in view of the shortage of design and application of acupuncture clinical trials at present, the authors paper put forward concrete control measures from aspects of subjective factors, objective factors and quality monitoring of acupuncture clinical trials, which are helpful to guarantee the quality of trials and could be reference for other researchers. The results indicate that strict quality control measures are the guarantee of high-quality acupuncture clinical trials.