Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer’s Disease

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

Feasibility of establishing cerebral ischemia models by using aerocyst-blocking bilateral ascending pharyngeal artery of piglets Imaging assessment

BACKGROUND: The cerebral ischemia and ischemia/reperfusion animal models are used to simulate the human cerebrovascular diseases is one of the popular topics of neurological science recently. To study the pathophysiology, pathogenesis, prophylaxis and treatment of ischemic cerebrovascular diseases and to establish the ideal animal model that is the most similar to the human cerebral ischemia, are the topics that the people generally cared about. OBJECTIVE: To evaluate the effects of aerocyst-blocking bilateral ascending pharyngeal artery on the establishment of cerebral ischemia models by using digital subtraction angiography (DSA), magnetic resonance diffusion-weighted imaging (DWI) and magnetic resonance perfusion-weighted imaging (PWI). DESIGN: Repetitive measure animal experiment. SETTING: Zhongshan Hospital Affiliated to Dalian University. MATERIALS: The experiment was carried out in the Animal Laboratory (Provincial Laboratory), Zhongshan Hospital of Dalian Univeristy from January to May 2006. A total of 14 domestic piglets, of 6 months old, weighing 12–15 kg, of either gender, were selected from Animal Experimental Center, Dalian University. Multistar T.O.P digital subtraction angiography machine was provided by Siemens Company, German. METHODS: Aerocyst-blocking bilateral ascending pharyngeal artery was used to establish cerebral ischemia models. And then, Multistar T.O.P. DSA was used for imaging of cerebral vessels before blocking, during blocking and at 0.5 and 2 hours after ischemia perfusion. GE Signa 1.5 T supraconduction magnetic resonance imaging was used for DWI examination; in addition, PWI was used based on focal sites and areas. Otherwise, magnetic resonance imaging (MRI) was used to detect signal changes of T1WI and T2WI in ischemic areas. MAIN OUTCOME MEASURES: Analytic results of DSA, DWI, PWI and MRI. RESULTS: All 14 experimental piglets were involved in the final analysis. ① DSA: The blood flow of bilateral ascending pharyngeal arteries and its branch were blocked at blocking phase, which restored 0.5 and 2 hours after reperfusion. ② DWI and PWI: There were no observable abnormalities in PWI and DWI at pre-blocking. Abnormal increased signals were found on both DWI and PWI at during and post-blocking. There were reduction in ADC and rCBF and delay in rTTP at all time points except pre-blocking. ③ MRI: There were no abnormal signals observable at any time of pre- and post-blocking in T1WI and T2WI. CONCLUSION: It is feasible to establish this kind of animal experimental models, and it can simulate the ischemic state; meanwhile, the existence and extent can be showed directly by DSA, DWI, and PWI.     

Clinical observation of Qi deficiency syndrome in 72 patients with chronic obstructive pulmonary disease treated with Yiqi Mianyi Granule

Seventy-two patients of chronic obstructive pulmonary disease (COPD) of Qi deficiency syndrome with abnormal immune indices were treated with Yiqi Mianyi Granule (YQMYG) and the efficacy was compared with that of 30 cases treated with Zhenqi fuzheng Granule (ZQFZG) for control. Results showed that the markedly effective rate of symptomatic improvement of Qi deficiency in YQMYG group was 65.3%, the total effective rate 93.1%. 88.6% of the immune indices lower than normal were corrected and 43. 7% of them were normalized, while for indices that were higher than normal the rate were 78.2% and 52.9% respectively. These results suggested that YQMYG could improve symptom of Qi Deficiency markedly, strengthen cellular immunity and regulate immune dysfunction. Its therapeutic efficacy was obviously superior to ZQFZG (P<0.Q5).     

PRENATAL DIAGNOSIS OF CONJOINED TWINSWI''TH REAL-TIME ULTRASOUNDA CASE REPORT

Conjoined twins case is a rare abnormality.The most common type of union is thoracopaguswhich is found in 75To of the cases. Conjoinedtwins have a sex predilection with 75Vo beingFcmale.i A case of conjoined twins was diagnoscdwith real-time ultrasonic scanner (Linear arraymodel, transducer 3.5 mHz) at the 21st week ofpcstation. Final.ly. it was shown late.r by po.slmor-tem examination after delivery that concurrentmalformation in head, hearts and aorta were pre-sent as previously seen on the ultrasonic imagcs.     

Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries. OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats. DESIGN: A randomized controlled animal trial. SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University. MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220–250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point. METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7–10 days. MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively. RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly expressed at 14 and 28 days, but decreased at 60 days, mainly located in the neurons of spinal cord gray matter anterior horn, and they expressed fewer in the motor neurons and white matter of ventral horn, and there were obvious differences between the estrogen-treated group and saline control group at 7, 14, 28 and 60 days (P < 0.05). CONCLUSION: Estrogen can reduce the apoptosis of nerve cells and promote the recovery of neurological function following gradual chronic spinal cord injury.     

Specificity and mechanism of the histone methyltransferase Pr-Set7

Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.     

PRQFVamide,a novel pentapeptide identified from the CNS and gut of Aplysia

We have purified a novel pentapeptide from the Aplysia nervous system using bioassay on gut contractions. The structure of the peptide is Pro-Arg-Gln-Phe-Val-amide (PRQFVa). The precursor for PRQFVa was found to code for 33 copies of PRQFVamide and four related pentapeptides. Peaks corresponding to the predicted masses of all five pentapeptides were detected in Aplysia neurons by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Northern analysis revealed that expression of the precursor is abundant in the abdominal ganglion, much less in the pedal and cerebral ganglia, and rarely seen in the buccal and pleural ganglia. PRQFVa-positive neurons, mapped by immunohistochemistry and in situ hybridization, were present in all the central ganglia. PRQFVa immunopositive processes were observed in the gut, particularly in association with the vasculature. Some arteries and other highly vascularized tissues, such as the gill and the kidney, also contain numerous PRQFVa immunopositive processes. Application of synthetic PRQFVa suppresses not only contractions of the gut but also contractions of vasculature. PRQFVa is expressed in some of the neurons within the feeding circuitry and application of synthetic PRQFVa was found to decrease the excitability of some (B4/5 and B31/32) but not all (B8) neurons of the buccal feeding circuit. Our findings suggest that PRQFVa may act as a modulator within the feeding system as well as in other systems of Aplysia.     

复苏早期应用氨茶碱对腺苷及血管活性因子的影响

目的： 观察心搏骤停大鼠复苏早期应用氨茶碱对复苏成功率、血浆去甲肾上腺素(NE)、腺苷、一氧化氮(NO)水平及心肌组织内皮素-1(ET-1)、腺苷水平的影响。方法: 选60只SD大鼠，随机分为3组：手术对照组、肾上腺素治疗组和肾上腺素+氨茶碱治疗组各20只。分别测定治疗组自主循环恢复30 min后及手术对照组的血浆NE、腺苷、NO及心肌组织ET-1、腺苷的水平。结果: 肾上腺素+氨茶碱治疗组自主循环恢复时间明显少于肾上腺素治疗组(P＜0.05)。肾上腺素+氨茶碱治疗组自主循环恢复率为75%，30 min存活率为70%，肾上腺素治疗组分别为60%和55% (P>0.05)。2个治疗组自主循环恢复大鼠的血浆腺苷、NE水平及心肌组织ET-1、腺苷水平均明显高于手术对照组(P<0.05)，肾上腺素治疗组血浆NO水平也显著高于手术对照组(P＜0.01)，肾上腺素+氨茶碱治疗组血浆NO及心肌组织ET-1水平低于肾上腺素治疗组(P＜0.05)。结论: 在复苏早期应用腺苷受体拮抗剂氨茶碱不仅可提高复苏成功率，并且降低血浆NO和心肌组织ET-1水平，有利于减轻复苏后综合征。