Effect of transient forebrain ischemia-reperfusion on the binding of brain-derived neurotrophic factor promoters to histone deacetylase 3 in hippocampus of rat and its mechanism / 中国生物制品学杂志

Transient forebrain ischemia-reperfusion(I/R);Brain-derived neurotrophic factor(BDNF);Histone deacetylase 3(HDAC3);Hippocampus@#Objective To evaluate the effect of transient forebrain ischemia-reperfusion(I/R)on the binding of brainderived neurotrophic factor(BDNF)promoters to histone deacetylase 3(HDAC3)in the hippocampus of rat and investigate its mechanism.Methods The I/R model of SD rats(I/R group)was established by Pulsinelli four-vessel clamping method,and sham operation group(Sham group)was set at the same time,which were observed for the survival of neurons in the hippocampus of rats by Nissl staining,detected for the binding of BDNF promoters(Bdnf-p1,Bdnf-p2,Bdnf-p4 and Bdnf-p6)to HDAC3 by chromatin immunoprecipitation(ChIP)and determined for the expression of brain derived neurotrophic factor antisense(BDNF-AS)by qPCR.Results Compared with Sham group,the quantity of neurons in hippocampal CA1 region of rats decreased significantly in I/R group,while those in CA3 region and DG region showed no significant changes.The binding levels of Bdnf-p1 and Bdnf-p2 to HDAC3 in hippocampal CA1 region decreased significantly in I/R Group(t = 2.575 and 2.241 respectively,each P<0.05),while there was no significant difference in the binding levels of Bdnf-p4 and Bdnf-p6 to HDAC3(t = 1.033 and 0.348 respectively,each P>0.05);The binding levels of Bdnf-p1 and Bdnf-p2 to HDAC3 in CA3 region increased significantly(t = 12.600 and 3.191,P<0.001 and<0.05,respectively),while the binding level of Bdnf-p6 to HDAC3 decreased significantly(t = 4.029,P<0.05)and no significant difference was observed in the binding level of Bdnf-p4 to HDAC3(t = 0.175,P>0.05);In DG region,the binding level of each BDNF promoter to HDAC3 showed no significantly difference(t = 0.630 ～ 1.687,each P>0.05).Meanwhile,the expression level of BDNF-AS in hippocampal CA1 region of rats decreased significantly(t = 2.560,P<0.05),but increased significantly in hippocampal CA3 and DG regions(t = 3.543 and 3.637 respectively,each P<0.01)in I/R group.Conclusion I/R showed a significant effect on the binding level of BDNF promoter to HDAC3 in rat hippocampus,which may play a role by changing the expression level of BDNF-AS.

Effects of DREADD-mediated inhibition of glutamatergic neurons in PVN on myocardial ischemia-reperfusion injury in mice / 中国药理学通报

Aim To explore the effeet of chemogenetic designer reeeptors exclusively activated by designer drugs( DREADD) mediated inhibition of glutamatergic neurons in paraventricular nucleus of hypothalamus (PVN ) on myocardial ischemia-reperfusion injury in mice.Methods Mice were catheterized in PVN by stereotaxic technique, followed by recover}' for three days in individual cages.The mice were then received the inhibitory virus rAAV CaMK E cx-hM4d (Gi)-EG- FP-WPRE-hGHpA or the control vims rAAV CaMK H a - E GF P- W PRE - h GH pA in the PVN nucleus.Three weeks after virus infection, myocardial ischemia-reperfusion injury ( IR) was performed by ligating the left anterior descending coronary artery for 1 h and then releasing it for 2 h.Clozapine N-oxide (CNO) 2 mg •kg 1 was injected intraperitoneally 1 h before IR, to induce inhibition of glutamatergic neurons in PVN by specifically binding to the hM4D receptor ( Gi).TTC staining was used to measure the infarct size, and ELISA was used to measure the serum cTnl concentration.During experiments, the ECG was recorded by PowerLab system.Western blot was used to detect the pro-survival kinase ERK and cleaved caspase-3 proteins in heart tissues, and the expressions of EGFP, CaMKII and c-fos in PVN were examined under fluorescence microscope.Results The glutamatergic neurons in PV N were specifically infected by AAV vectors.When compared with sham group, the ratio of IS/AAR, serum cTnl, c-fos in PVN, and cleaved caspase-3 protein all increased in IR group , but the pERK level decreased.However, hM4D ( Gi) DREADD mediated inhibition of PVN glutamatergic neurons significantly reduced IS/AAR, cTnl concentration and c-fos expression in PVN, as well as the decrease of cleaved caspase-3 and the increase of pERK in heart tissues.Conclusion Chemogenetic DREADD mediated inhibition of glutamatergic neurons in paraventricular nu- cleus of hypothalamus ( PVN) reduces myocardial is- chemia-reperfusion injury in mice.

Progress of cancer-testis antigen in lung cancer / 肿瘤研究与临床

At present, lung cancer has entered a new era of immunotherapy. However, a single immunotherapy is unable to satisfy the requirements of the immune microenvironment. More and more different combined immunotherapy schemes have become effective methods to overcome immune resistance. As a promising target in the novel immunotherapy, cancer-testis antigen (CTA) is a highly specific tumor antigen to produce a powerful anti-tumor immune response that is almost only expressed in malignant tumors. This article reviews the research progress of CTA's expression, function and immunotherapy application in lung cancer.

Comparison of intermittent fasting diet and continuous energy-restricted diet on weight loss and metabolic profile in overweight people / 中华临床营养杂志

Objective To compare the weight loss and metabolic profile between a continuous energyrestricted diet and intermittent fasting diet in order to present an optimal nutritional weight reduction method for obese people in China. Methods Sixty overweight or obese adults were selected and divided into two groups as the continuous energy-restricted diet group and the intermittent fasting diet group. Height, weight, waist circumference, body mass index (BMI), body fat, change of visceral fatarea, fasting glucose (FPG), triglyceride (TG), total cholesterol ( TC), high density cholesterol ( HDL), low density cholesterol (LDL), glutamic pyruvicaminotransferase ( AST), signglutamic pyruvic transaminase ( ALT), gammaglutamyltranspeptidase (GGT), alkalinephosphatase (ALP), fasting insulin level (FINS) and HOMA-IR were assessed at baseline and 8 weeks after weight loss methods carried. Results Both continuous energy-restricted diet and intermittent fasting diet resulted improvement on body shape indexes and a significant decrease in weight, waist circumference, BMI, body fat, visceral fat area and skeletal muscle (P<0. 01) at 8 weeks. Both groups experienced improvements in biochemical outcomes and metabolic indicators at 8 weeks. A significant reduction in TC, AST, ALT, GGT, ALP, FINS and HOMA-IR (P<0. 01 or P<0. 05) were observed in continuous energy-restricted diet group. And a significant decline in TC, LDL, HDL, AST, ALT, GGT, ALP, FINS and HOMA-IR were observed in intermittent fasting diet group (P <0. 01 or P < 0. 05). HDL was found significantly reduced in intermittent fasting diet group as compared with continuous energy-restricted diet group (P<0. 01) at 8 weeks, however, there were no difference in weight loss, waist circumference, BMI, body fat, visceral fat area and other metabolic indicators at 8 weeks (P>0. 05). Conclusion Both intermittent fasting diet and continuous energy-restricted diet have a similar effect on weight loss and metabolic indexes like blood glucose, HOMA-IR and blood lipid, but intermittent fasting diet can more significantly decrease HDL level.

Prevention and treatment of bariatric postoperative longterm complications / 中国实用外科杂志

In recent years,bariatric surgery has developed rapidly in China,and its surgical procedures are constantly being innovated. But the postoperative complications do not reduce. Each new kind of surgery brings new problems,and each new bariatric center established brings new test. Some long-term complications are emerging with the extension of time for bariatric postoperative follow-up in China. Metabolic surgeon should pay more attention to the prevention of postoperative complications. Only by analyzing and solving the developing problems can make postoperative complications be effectively prevented.

Mechanism of metabolic surgery mediated FGF21 in improving insulin resistance / 国际外科学杂志

Insulin resistance refers to a decrease in the physiological utilization of normal concentrations of insulin by target organs such as liver and adipose tissue.Insulin resistance is central to a variety of metabolic diseases caused by obesity.FGF21 is a novel regulator of glycolipid metabolism,which has the effects of improving insulin resistance,reducing body weight,regulating blood lipids,promoting fatty acid oxidation,and increasing energy consumption.Metabolic surgery is effective in the treatment of obesity and insulin resistance,and the level of FGF21 changes after surgery.This article will review the possible mechanisms of metabolic surgery to mediate FGF21 to improve insulin resistance.

Establishment of a model of dihydrotestosterone-induced polycystic ovary syndrome complicated with atherosclerosis in rats / 中国基层医药

Objective@#To establish a rat model of polycystic ovary syndrome(PCOS) complicated with atherosclerosis(AS).@*Methods@#Sixteen female SD rats were selected and randomly divided into control group and model group, with 8 rats in each group.The rats in the control group were given routine rearing.The rats in the model group were subcutaneously given dihydrotestosterone(DHT) in neck and fed with high fat diet for a long term.The changes of food intake (FI), body weight(BW), testosterone (T), estrogen (E2), luteinizing hormone (LH), total cholesterol (TC), blood glucose (BG) and insulin (INS) were observed in the two groups.@*Results@#The levels of FI, T, E2, LH between the control group and model group had no obvious change[(86.13±7.83)g/r vs.(96.25±10.66)g/r, t=2.113, P=0.563, (10.79±1.74)mg/L vs.(11.47±1.89)mg/L, t=1.785, P=0.087; (36.58±2.57)ng/L vs.(38.64±1.78)ng/L, t=2.697, P=0.068; (15.47±1.96)IU/L vs.(16.01±0.80)IU/L, t=1.570, P=0.614]. The levels of BW, TC, DHT, INS in the model group were significantly higher than those in the control group[(234.54±17.14)g vs.(192.67±16.47)g, t=7.930, P<0.000; (2.47±0.13)mmol/L vs.(2.02±0.15)mmol/L, t=6.475, P<0.000; (139.75±12.12)ng/L vs.(55.63±7.80)ng/L, t=8.697, P<0.000; (283.25±33.47)pg/mg vs.(162.12±15.51)pg/mg, t=9.289, P<0.000]. Tube wall was markedly thickened in the model group after being given high fat feed for 12 weeks, and intimal wall was significantly thickened after 16 weeks, and endotheliocyte injury, deep collagen fiber, monocyte adhesion, visible atherosclerotic plaques were observed in the model grouop.@*Conclusion@#DHT-induced PCOS rat model by high fat feed reproduces the human typical clinical symptoms and pathological characteristics, it can provide a relatively simple and feasible rat model for further study of the mechanism of PCOS complicated with AS.

Role of peripheral vestibular receptors in the control of blood pressure following hypotension

Hypotension is one of the potential causes of dizziness. In this review, we summarize the studies published in recent years about the electrophysiological and pharmacological mechanisms of hypotension-induced dizziness and the role of the vestibular system in the control of blood pressure in response to hypotension. It is postulated that ischemic excitation of the peripheral vestibular hair cells as a result of a reduction in blood flow to the inner ear following hypotension leads to excitation of the central vestibular nuclei, which in turn may produce dizziness after hypotension. In addition, excitation of the vestibular nuclei following hypotension elicits the vestibulosympathetic reflex, and the reflex then regulates blood pressure by a dual-control (neurogenic and humoral control) mechanism. In fact, recent studies have shown that peripheral vestibular receptors play a role in the control of blood pressure through neural reflex pathways. This review illustrates the dual-control mechanism of peripheral vestibular receptors in the regulation of blood pressure following hypotension.

Construction of artesunate nanoparticles modified by hyaluronic acid and cell-penetrating peptides and its inhibitory effect on cancer cells in vitro / 中国中药杂志

Hyaluronic acid (HA) and cell-penetrating peptide (CPP) R6H4-SA modified artesunate nanostructured lipid carrier (HA-R6H4-NLC/ART) for anti-tumor therapy was prepared. The physicochemical properties and in vitro drug release of HA-R6H4-NLC/ART were evaluated, and the uptake and cytotoxicity of liver cancer HepG2 cells were studied. The results showed that HA-R6H4-NLC/ART was spherical like in appearance, and the average particle size was about 160 nm. In vitro release experiments showed that the drug delivery system had sustained release characteristics. Cell results showed that, in slightly acidic environment, pH sensitive CPP R6H4-SA mediated cellular uptake of nanoparticles was significantly higher than that of non-sensitive peptide R8-SA. Meanwhile, HA-R6H4-NLC/ART had a targeting effect on HepG2 cells, and the HA receptor saturation experiment showed that the endocytosis of HA-R6H4-NLC/ART was mediated by the HA receptor on the cell surface. As compared with the unmodified or R6H4-SA single modified group, HA and R6H4-SA co-modified HA-R6H4-NLC/ART significantly improved the cell uptake and had a stronger anti-tumor effect under the conditions of the slightly acid environment and hyaluronidase degradation. The above results showed that hyaluronic acid and CPP R6H4-SA co-modified artesunate nanostructured lipid carrier, which can effectively identify and penetrate the tumor cell membrane into the cell, is a potentially efficient targeting delivery system for anti-tumor drugs.

Effects of tetramethylypyrazine nitrone on proliferation and differentiation of neural stem cells / 中国应用生理学杂志

OBJECTIVES@#To investigate the role of tetramethylpyrazine(TMP) nitrone in proliferation and differentiation of neural stem cells (NSCs).@*METHODS@#We separated and cultivated the original generation of NSCs from cerebral cortex of 14 days rat embryo, and the phenotype characteristics of the third-generation NSCs was tested by immunofluorescence. The experiment was divided into control group, β-mercaptoethanol positive control group, tetramethylpyrazine nitrone group and tetramethylpyrazine nitrone + ethylene glycol tetraacetic acid(EGTA) group (=4). The third-generation cultivation of NSCs was used in the experiment. The effect of tetramethylpyrazine nitrone on the number of NSCs proliferation was determined by BrdU and MTT, and the differentiation of NSCs was determined by Western blot.@*RESULTS@#The primary NSCs was isolated successfully, neurospheres with typical NSCs morphology and expressing nestin was formed at 3-5 days. As BrdU and MTT assay results shown, compared with the control group andβ-mercaptoethanol positive control group, the NSCs proliferation numbers of tetramethylpyrazine nitrone group increased significantly(<0.05). The results of Western blot showed that the neuronal differentiation rate of NSCs was increased significantly in both the tetramethylpyrazine nitrone group and tetramethylpyrazine nitrone + EGTA group, and the differentiation rate of NSCs in tetramethylpyrazine nitrone + EGTA group increased more significantly(<0.05).@*CONCLUSIONS@#Tetramethylpyrazine nitrone can significantly enhance the proliferation and neuronal differentiation rate of NSCs. Decrease in extracellular Ca can promote the differentiation of NSCs into neurons induced by tetramethylpyrazine nitrone. Ca signaling plays an important role in the differentiation of NSCs into neurons.

Prognostic value of lymphocyte-to-monocyte ratio in the patients with malignant tumor / 实用肿瘤学杂志

Inflammation has a critical role in the pathogenesis and progression of cancer.lymphocyte and monocyte play an important role in inflammatory reaction,reflecting body immune status.In recent years,more and more clinical studies have shown that pretreatment of lymphocyte-to-monocyte ratio(LMR)in the patients with malignant tumor may have a certain value in evaluating the prognosis of cancer patients such as nasopharyngeal cancer,esophageal cancer,breast cancer,ovarian cancer,lung cancer,gastric cancer,colorectal cancer,etc.This article reviews the latest research progress on the value of LMR in the evaluation of the prognosis of the patients with malignant tumor.

Arginase Level in Apheresis Leukocyte-Reduced Platelets Stored for Different Time / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of storage time on arginase level and possible source of arginase in apheresis leukocyte-reduced platelets(ALR-Plt).</p><p><b>METHODS</b>The arginase level and myeloperoxidase(MPO) levels in ALR-Plt and control plasma were detected by ELISA. The relationship between arginase level and MPO level in ALR-Plt was analyzed by correlation analysis.</p><p><b>RESULTS</b>There was no significant difference of arginase level between ALR-Plt stored less than 3 days and control plasma. However, arginase level in ALR-Plt stored over 3 days was significantly higher than that in ALR-Plt stored less than 3 days and control plasma(P<0.05). There was no significant difference of MPO level in ALR-Plt stored for different times, but the MPO level in ALR-Plt stored for different time was lower than that in control plasma. Correlation analysis showed that arginase level positively correlated with MPO level in ALR-Plt of different storage time (r=0.58).</p><p><b>CONCLUSION</b>The arginase level in ALR-Plt stored over 3 days increase significantly. The main possible source of arginase in ALR-Plt is the residual white blood cells, especially neutrophils.</p>

Research progress on patient-derived xenograft models of lung cancer / 中国肿瘤临床

Patient-derived xenograft models (PDXs) of lung cancer are obtained by directly implanting lung cancer tissue fragments in-to immunocompromised mice. The implanted tumor fragments can be proliferated and passaged in these mice models. The PDXs maintain the tumor microenvironment, histological and pathological characteristics, and tumor biomarkers of the original tumor tis-sues. The PDX also offers an ideal mice model that mimics the human tumor microenvironment. These models have important roles in the pre-clinical evaluation of cancer, the assessment of anti-tumor drug responses, and the analysis of biomarkers. These models also present a new direction for the individualized therapy of lung cancer patients.

Pathways of Neurogenic and Humoral Control in the Vestibulosympathetic Reflex of Conscious Rats / 대한평형의학회지

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.

Prevalence and diagnosis rate of intra-abdominal hypertension in critically ill adult patients: A single-center cross-sectional study / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To investigate the prevalence and diagnosis rate of intra-abdominal hypertension (IAH) in a mixed-population intensive care unit (ICU), and to investigate the knowledge of ICU staff regarding the guidelines published by the World Society of Abdominal Compartment Syndrome (WSACS) in 2013.</p><p><b>METHODS</b>A one-day cross-sectional study based on the WSACS 2013 guidelines was conducted in the general ICU of a tertiary teaching hospital in Chongqing, China. The included patients were divided into intravesical pressure (IVP) measured group and IVP unmeasured group. The epidemiologic data were recorded, and potential IAH risk factors (RFs) were collected based on the guidelines. IVP measurements were conducted by investigators every 4 h and the result was compared to that measured by the ICU staff to evaluate the diagnosis rate. Besides, a questionnaire was used to investigate the understanding of the guidelines among ICU staff.</p><p><b>RESULTS</b>Thirty-two patients were included, 14 in the IVP measured group and 18 in the IVP unmeasured group. The prevalence of IAH during the survey was 15.63% (5/32), 35.71% (5/14) in IVP measured group. Only one case of IAH had been diagnosed by the ICU physician and the diagnosis rate was as low as 20.00%. Logistic regression analysis showed that sequential organ failure assessment (SOFA) score was an independent RF for IAH (OR: 1.532, 95% CI: 1.029-2.282, p=0.036. Fourteen doctors and 5 nurses were investigated and the response rate was 67.86%. The average scores of the doctors and nurses were 27.14±20.16 and 16.00±8.94 respectively. None of them had studied the WSACS 2013 guidelines thoroughly.</p><p><b>CONCLUSION</b>Patients with a higher SOFA score has a higher incidence of IAH. The IAH prevalence in 14 ICU patients with indwelling catheter was 35.71%. Strengthening the wide and rational use of WSACS guideline is important to improve the diagnosis of IAH.</p>

Textual research for Tibetan medicine Qumazi / 中国中药杂志

Qumazi is a commonly used Tibetan medicine. With a long history, it can be found in the Four Medical Tantras written by gYu-thog rNying-ma Yon-tan mGon-po since the 8th century AD. Qumazi grows in mudflats and fields, including species growing in highlands, lowlands, mountains and farmlands. According to records in Crystal Beads Materia Medica, it features green sword-shaped leaves, thin stems with red veins, inserted panicles, white chicken-like flowers and copper needle row-like roots. However, there are many inconsistent morphological descriptions for Qumazi plants in many Chinese versions of Tibetan medicine books. In this article, after studying ancient and modern Tibetan medicine books, consulting experts and conducting surveys, the authors confirmed that Qumazi belongs to Rheum of Polygonaceae, including Rheum nobile Hook. f. et. Thoms, R. globulosum Gage, R. alexandrae Hook. f. et. Thoms, R. pumilum Maxim and R. delavayi Franch. In some regions, Qumazi is substituted by R. spiciforme Royle and R. przewalskyi Losinsk. After the Chinese version of Qinghai-Tibet Plateau Drug Illustrations was published in 1972, Qumazi has been miswritten as P. sibiricum Laxm in many Chinese versions of Tibetan medicine books, perhaps because P. sibiricum Laxm has many similar features with Qumazi as described in Crystal Beads Materia Medica and then is mistranslated from Tibetan to Chinese versions. According to records, Qumazi can reduce edema and is mainly applied to treat the minamata disease in clinic.

Arginase Level in Suspended Red Blood Cells Storaged for Different Time / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of storage time on arginase level, and the possible source of arginase in suspended red blood cells (RBC).</p><p><b>METHODS</b>The arginase and myeloperoxidase (MPO) levels in suspended RBC and control plasma were detected by ELISA. The free hemoglobin level in suspended RBC and control plasma were detected by colorimetric method. The relationship between arginase level, MPO level and free hemoglobin level in suspended RBC was analyzed by the related methods.</p><p><b>RESULTS</b>The arginase and free hemoglobin levels in suspended RBC were higher than those in control plasma. Otherwise, MPO level was not significantly different between suspended RBC and control plasma. All of them did not increase along with prolonging of storage time. There was not a significant correlation between arginase level and free hemoglobin level in suspended RBC of different storage time (r = 0.03), but arginase level positively correlated with MPO level in the suspended RBC of different storage time (r = 0.76).</p><p><b>CONCLUSION</b>The arginase level in suspended RBC storaged for different time increases significantly, but not along with prolonging of storage time. The main possible source of arginase in the suspended RBC is the residual white blood cell, especially neutrophils.</p>

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.

Effect of Glutamate on the Vestibulo-Solitary Projection after Sodium Nitroprusside-Induced Hypotension in Conscious Rats

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

The advances of the HSP90 inhibitor NVP-AUY922:applied alone or in combination with anti-tumor treatment / 实用肿瘤学杂志

Heat shock protein 90(Hsp90)is a highly conserved protein which have been proved to play an important role in the development and progression of malignant transformation .As one of small molecule inhibi-tors that has been detected to have potent antitumor activity in a wide range of malignancies ,NVP-AUY922 is a pyrazole scaffold drug with many advantages such as low toxicity and stable structure .As a result of this,NVP-AUY922 is extensively considered as a new promising kind of anti -tumor drug .This review intends to update the reader on advances made over the past four years in the clinical development of NVP -AUY922 in advanced cancers.