Quantitative Mitochondrial Proteomics Study on Protective Mechanism of Grape Seed Proanthocyanidin Extracts Against Ischemia/Reperfusion Heart Injury in Rat

Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.

Early diagnosis, treatment, and outcomes of five patients with acute thallium poisoning

BACKGROUND Thallium poisoning is rare and difficult to recognize.Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality.AIM To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning.METHODS Five patients who consumed a thallium-contaminated meal were hospitalized in succession,and underwent clinical examinations such as blood tests and electromyography tests.Urine and blood tests confirmed the diagnosis of thallotoxicosis,revealing the occurrence of food poisoning.All patients underwent detoxification treatment,including hemoperfusion(HP)and treatment with Prussian blue(PB).A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge.RESULTS Initially,the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia,which may differ from common peripheral neuropathy.Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients,which further confirmed the diagnosis of poisoning.Treatment with chelating agents was ineffective,while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood.With early diagnosis and intervention,four patients had a good prognosis and no permanent sequelae.One patient developed blindness and disability during the 24-mo follow-up period.CONCLUSION Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning.HP plus PB is essential to improve the prognosis of thallium-poisoned patients.

A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats

Background Diabetic retinopathy （DR） is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts （GSPE） have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes. Methods We used streptozotocin （STZ） to induce diabetes in rats. GSPE （250 mg/kg body weight per day） were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products （AGEs） were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats. Results GSPE significantly reduced the AGEs of diabetic rats （P 〈0.05）. Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism. Conclusions These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

Effects of phlorizin on vascular complications in diabetes db/db mice

Background Diabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus （T2DM）. Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism. Methods Diabetic db/db mice （n=16） and age-matched db/m mice （n=8） were divided into three groups： normal control group （CC group, db/m mice, n=8）, untreated diabetic group （DM group, db/db mice, n=8） and diabetic group treated by phlorizin （DMT group, db/db mice, n=8）. Phlorizin （20 mg/kg body weight） was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose （FBG）, serum advanced glycation end products （AGEs）, malondialdehyde （MDA） and superoxide dismutase （SOD） activity, the aortic ultrastructure was studied. Results The weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group （P 〈0.01 ）, and they were significantly lower in the DMT group （P 〈0.05）. Serum SOD activity was lower than that in the CC group （P 〈0.01）, and it is significantly higher in the DMT group （P 〈0.05）. The severity of aorta damage in the DMT group was less than that in the DM group. Conclusions Phlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.

Primary angiitis of the central nervous system： a case report

Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages.

Proliferating cell nuclear antigen involved in the repair process of ouabain-induced brain damage independent of hypertension in rats

Background Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity.It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase.Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen （PCNA） plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis.Therefore,we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension.And PCNA might be involved in this process.Methods Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group.Systolic blood pressure was recorded weekly.After four weeks of treatment,morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy.The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry,real time quantitative PCR,and Western blotting.Results After 4-week treatment,there was no significant difference in systolic blood pressure compared with the control group,but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment.Conclusions These results suggest that ouabain induces alterations in the brain structure,and this effect is independent of blood pressure.PCNA might be involved in the repair process of ouabain-induced brain damage.

Longitudinal cognitive dysfunction in patients with obstructive sleep apnea syndrome after transient ischemic attack

To the Editor:Obstructive sleep apnea syndrome(OSAS)is characterized by repetitive episodes of upper airway obstruction(partial or complete)during sleep,which leads to recurrent arterial hypoxemia and sleep fragmentation.Untreated OSAS in middle-aged patients cause impair-ments in attention,vigilance,some aspects of memory,and executive function.[1]Transient ischemic attack(TIA)is characterized by a transient episode of neurological dysfunction caused by focal brain ischemia.By definition,TIA should not bring persistent deficits but it does increase the risk of long-term cognitive impairment.

匹伐他汀钙对高胆固醇血症患者动脉粥样硬化的影响（英文）

目的：观察匹伐他汀钙对高胆固醇血症患者外周血管的影响。创新点：首次在国内发现匹伐他汀钙能够改善高胆固醇血症患者肱动脉和颈动脉血管内皮功能而且延缓其动脉粥样硬化发展，并首次证实改善内皮功能是匹伐他汀钙延缓其动脉粥样硬化发展的重要原因。方法：按照入选排除标准，选取本院高胆固醇血症患者（HC），完成超声心动图检查的40例。根据剂量不同，分为两个剂量组：1 mg剂量组20例（男性5例，女性15例，平均年龄（55.20±8.35）岁），2 mg剂量组20例（男性9例，女性11例，平均年龄（57.56±6.09）岁）。访视结束后完成超声心动图检查的HC组36例，两个剂量组分别有2人失访。治疗后1 mg剂量组18例（男性3例，女性15例，平均年龄（56.00±7.85）岁），2 mg剂量组18例（男性7例，女性11例，平均年龄（57.79±6.46）岁）。选择本院同期体检中心30例正常人作为对照（年龄和性别均与病例组匹配，男性14例，女性16例，平均年龄（54.94±6.90）岁）。所有研究对象，均经隔夜禁食12～14小时，次日清晨抽取空腹肘静脉血，测定临床生化指标。采用Sequia 512彩色多普勒超声诊断仪，应用高分辩率外周血管超声技术，检测HC治疗前后肱动脉血流介导性舒张功能（FMD）、颈动脉结构和功能。 结论：经匹伐他汀钙治疗8周后，高胆固醇血症患者血管功能明显改善，表现为 FMD升高，僵硬度减小；颈动脉僵硬度和内中膜厚度（IMT）延缓进展与其内皮功能改善密切相关。

Myotonic Dystrophy Type I with Syringomyelia in a Young Patient

Myotonic dystrophy type 1 （DM1） is the most common disease causing muscle weakness and atrophy in adults. The prevalence of DM1 in China is not clear. DM1 is an autosomal dominant genetic disorder associated with the cytosine-thynline-guanine （CTG） repeat expansion in 3＇untranslated region in dystrophia myotonica-protein kinase （DMPK） gene on chromosome 19q 13.3. In DM 1, CTG pathological repeat numbers are more than 50. The size of CTG repeat expansion is associated with the time of clinical phenotypes onset and severity The coexistence of DMI and syrlngomyelia is rare. Here, we report DM1 coexisting with syringonlyelia in a Chinese male patient.