Prognostic analysis of oral cancer based on deep learning / 口腔疾病防治

@#TNM（tumor node metastasis）classification is a common way to evaluate the prognosis of patients with oral cancer; however, many years of application have proven this method to be confined merely in clinical and pathological data and it cannot be adapted to the development of modern medicine. Deep learning (DL) has been widely used in various aspects of human life, has advantages for conducting efficient and intelligent searches and can explore and analyze substantial medical information well. Additionally, the application of DL to medical practice is quickly increasing. In the field of oral cancer prognosis, DL can efficiently process and analyze the pathological, radiographic and molecular data of oral cancer patients represented by lymphocytes, gray level cooccurrence matrix (GLCM) and gene maps and make accurate prognostic judgments accordingly. By assisting physicians in optimizing treatment plans, DL can effectively improve patients’ survival. Although DL lacks sufficient data and practical clinical application in prognostic studies, it has shown good clinical application prospects.

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial / 中华医学杂志(英文版)

BACKGROUND@#The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.@*METHODS@#A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency.@*RESULTS@#In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785).@*CONCLUSIONS@#As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD.@*TRIAL REGISTRATION@#chictr.org.cn, No. ChiCTR-TRC-12003513.

UC-MSCs affects apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway / 中国肿瘤生物治疗杂志

@#Objective: To investigate the effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway, and to explore the mechanism. Methods: UCMSCs were isolated from human umbilical cord tissues by enzyme digestion method and cultured in vitro. The immunophenotypes of the obtained MSCs were identified by flow cytometry. The culture supernatant of UC-MSCs was collected to establish an indirect in vitro co-culture system of UC-MSCs conditioned medium and lung adenocarcinomaA549 cell line. Proliferation ofA549 cells was detected by CCK-8 assay; apoptosis ofA549 cells was determined byAnnexin V/PI double staining, and cell cycle distribution of tumor cells was determined by PI staining. The transcription levels of apoptosis and proliferation associated downstream genes in the PI3K/AKT pathway, such as CyclinD1, BAX and Bcl-2, were detected by quantitative polymerase chain reaction (qPCR). Moreover, Wb was utilized to detect the expression levels of PI3K/AKT pathway-related proteins. Results: The culture flask was filled with fibroblast-like cells, arranged in parallel, with spiral growth after three weeks of isolation and culture of human umbilical cord tissues. The flow cytometry results revealed that the MSC markers CD73, CD90 and CD105, but not CD45 and HLA-DR, were expressed on obtained cells.After indirect in vitro co-culture of UC-MSCs conditioned medium and lung adenocarcinoma A549 cells, the proliferation rate of A549 cells was significantly decreased; the apoptosis rate was significantly increased, and the cell cycle was obviously arrested at the G1 phase as compared with the control group (all P<0.01). The transcription levels of PI3K/AKT signaling pathway-related factors, CyclinD1 and Bcl-2 were down-regulated, and the transcription level of BAX was up-regulated (all P<0.01). The total AKT was not changed, but p-AKT protein expression was decreased in a dose-dependent manner inA549 cells cultured in UC-MSCs conditioned medium (P<0.01). Conclusion: UC-MSCs can affect the proliferation and the apoptosis of A549 cells, and arrest cells in G1 phase. The main mechanism is that UC-MSCs can inhibit the PI3K/AKT signaling pathway in A549 cells, providing an experimental basis for exploring the safety and effectiveness of clinical application of UC-MSCs.

Mesenchymal Stem Cell Therapy for Bone Regeneration

Mesenchymal stem cells (MSCs) have been used in clinic for approximately 20 years. During this period, various new populations of MSCs have been found or manipulated. However, their characters and relative strength for bone regeneration have not been well known. For a comprehensive understanding of MSCs, we reviewed the literature on the multipotent cells ranging from the definition to the current research progress for bone regeneration. Based on our literature review, bone marrow MSCs have been most widely studied and utilized in clinical settings. Among other populations of MSCs, adipose-derived MSCs and perivascular MSCs might be potential candidates for bone regeneration, whose efficacy and safety still require further investigation.

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.

Influence of two-child policy on mode of delivery / 医学研究生学报

Objective Less research has been done in the influence of two-child pohcy on mode of delivery.The article aimed to investigate the rates of cesarean section before and after two-child policy along with indications and complications in order to provide scientific basis and solution for improving the vaginal delivery rate.Methods Retrospective analysis was conducted on medical record data of 7044 puerperas in Nanjing General Hospital of Nanjing Military Region before (3,526 women from January 1,2012 to December 31,2013)and after (3,518 women from January 1,2015 to December 31,2016) two-child policy.Before the two child policy there were 3122 primiparas and 404 multiparas,after two-child policy there were 2546 primiparas and 972 muhiparas.Comparison was done between two groups in the aspect of vaginal delivery rate,cesarean section rate and the distribution of primiparas in choosing the mode of delivery.Results The vaginal birth rate of women before and after the policy was 59.22％ and 63.22％ respectively,among which the rate of vaginal delivery of primiparas increased dramatically from 60.57％ before the policy to 66.10％ after the policy(P＜0.05).After two-child policy,the primiparas cesarean section indication with social factors,macrosomia decreased,which was 12.67％ vs 5.68％、16.65％ vs 11.82％,respectively.However,the rate of cesarean section with in-vitro fertilization increased,which was 5.52％ and 10.10％ respectively (P ＜ 0.05).Conclusion After two-child policy,the puerperant,especially for the primiparas were more likely to choose vaginal spontaneous delivery.At the same time,the proportion of the primiparas caesarean section also changed.The mode of delivery should depend on corresponding indications properly.

Update and extension of the Brazil SimSmoke model to estimate the health impact of cigarette smoking by pregnant women in Brazil / Atualização e extensão do modelo SimSmoke para estimar o impacto do tabagismo na saúde das gestantes brasileiras / Actualización y extensión del modelo SimSmoke para estimar el impacto del tabaquismo en la salud de las gestantes brasileñas

Abstract: A previous application of the Brazil SimSmoke tobacco control policy simulation model was used to show the effect of policies implemented between 1989 and 2010 on smoking-attributable deaths (SADs). In this study, we updated and further validated the Brazil SimSmoke model to incorporate policies implemented since 2011 (e.g., a new tax structure with the purpose of increasing revenues/real prices). In addition, we extended the model to estimate smoking-attributable maternal and child health outcomes (MCHOs), such as placenta praevia, placental abruption, preterm birth, low birth weight, and sudden infant death syndrome, to show the role of tobacco control in achieving the Millennium Development Goals. Using data on population, births, smoking, policies, and prevalence of MCHOs, the model is used to assess the effect on both premature deaths and MCHOs of tobacco control policies implemented in Brazil in the last 25 years relative to a counterfactual of policies kept at 1989 levels. Smoking prevalence in Brazil has fallen by an additional 17% for males (16%-19%) and 19% for females (14%-24%) between 2011 and 2015. As a result of the policies implemented since 1989, 7.5 million (6.4-8.5) deaths among adults aged 18 years or older are projected to be averted by 2050. Current policies are also estimated to reduce a cumulative total of 0.9 million (0.4-2.4) adverse MCHOs by 2050. Our findings show the benefits of tobacco control in reducing both SADs and smoking-attributable MCHOs at population level. These benefits may be used to better inform policy makers in low and middle income countries about allocating resources towards tobacco control policies in this important area.

Resumo: Foi utilizada uma versão anterior do modelo SimSmoke, de simulação de políticas de controle do tabagismo, para mostrar o efeito das políticas implementadas entre 1989 e 2010 sobre a mortalidade atribuível ao tabagismo (MAT). O estudo atualiza e estende a validação do modelo SimSmoke para incorporar as políticas implementadas a partir de 2011 (p.ex.: uma nova estrutura tributária com o objetivo de aumentar os impostos e preços reais do produtos de tabaco). Estendemos o modelo também para estimar os danos à saúde materna e infantil atribuíveis ao tabagismo, como placenta prévia, descolamento prematuro da placenta, prematuridade, baixo peso ao nascer e síndrome da morte súbita infantil, para demonstrar o papel do controle do tabagismo no cumprimento dos Objetivos do Milênio. O modelo usa dados demográficos, de nascimentos, de tabagismo, de políticas e de prevalência de desfechos maternos e infantis para avaliar o efeito das políticas de controle do tabagismo dos últimos 25 anos sobre mortes prematuras e danos à saúde materna e infantil, comparado a um cenário contrafatual de manutenção das políticas nos níveis de 1989. Entre 2011 e 2015, a prevalência do tabagismo no Brasil caiu em mais 17% entre homens (16%-19%) e 19% em mulheres (14%-24%). Como resultado das políticas lançadas desde 1989, estima-se que até 2050 serão evitadas 7,5 milhões (6,4-8,5 milhões) de mortes entre adultos com 18 anos ou mais. Estima-se também que as políticas atuais reduzirão um total acumulado de 0,9 milhão (0,4-2,4 milhões) de desfechos adversos de saúde materna e infantil até 2050. Nossos achados demonstram os benefícios do controle do tabagismo na redução da MAT e de danos à saúde materna e infantil atribuíveis ao tabagismo em nível populacional. Esses benefícios podem ser utilizados para informar os gestores nos países de renda baixa e média sobre a alocação de recursos para as políticas de controle do tabagismo.

Resumen: Se utilizó una versión anterior del modelo SimSmoke, de simulación de políticas de control del tabaquismo, para mostrar el efecto de las políticas implementadas entre 1989 y 2010 sobre la mortalidad atribuible al tabaquismo (MAT). El estudio actualiza y extiende la validación del modelo SimSmoke para incorporar las políticas implementadas a partir de 2011 (p. ej., una nueva estructura tributaria con el objetivo de aumentar los impuestos y precios reales de productos de tabaco). Extendemos el modelo también para estimar los daños a la salud materna e infantil atribuibles al tabaquismo, como placenta previa, desprendimiento prematuro de la placenta, prematuridad, bajo peso al nacer y síndrome de muerte súbita infantil, para demonstrar el papel del control del tabaquismo en el cumplimiento de los Objetivos del Milenio. El modelo usa datos demográficos, de nacimientos, de tabaquismo, de políticas y de prevalencia de desenlaces maternos e infantiles para evaluar el efecto de las políticas de control del tabaquismo de los últimos 25 años sobre muertes prematuras y daños a la salud materna e infantil, comparado con un escenario contrafáctico de mantenimiento de las políticas a los niveles de 1989. Entre 2011 y 2015, la prevalencia del tabaquismo en Brasil disminuyó en más de un 17% entre hombres (16%-19%) y 19% en mujeres (14%-24%). Como resultado de las políticas lanzadas desde 1989, se estima que hasta 2050 se evitarán 7,5 millones (6,4-8,5 millones) de muertes entre adultos con 18 años o más. Se estima también que las políticas actuales reducirán un total acumulado de 0,9 millones (0,4-2,4 millones) de desenlaces adversos de salud materna e infantil hasta 2050. Nuestros hallazgos demuestran los beneficios del control del tabaquismo en la reducción de MAT y de los daños a la salud materna e infantil, atribuibles al tabaquismo en nivel poblacional. Esos beneficios pueden ser utilizados para informar a los gestores en los países de renta baja y media sobre la asignación de recursos para las políticas de control del tabaquismo.

A Meta analysis of the efficacy of high-frequency oscillatory ventilation versus conventional mechanical ventilation for treating pediatric acute respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To systematically assess the clinical efficacy of high-frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) for treating pediatric acute respiratory distress syndrome (ARDS).</p><p><b>METHODS</b>Data from randomized controlled trials comparing HFOV and CMV in the treatment of pediatric ARDS published before July 2016 were collected from the Cochrane Library, PubMed, Medline, CNKI, and Wanfang Data. Literature screening, data extraction, and quality assessment were performed by two independent reviewers according to the inclusion and exclusion criteria. The selected studies were then subjected to a Meta analysis using the RevMan 5.3 software.</p><p><b>RESULTS</b>A total of 6 studies involving 246 patients were included. The results of the Meta analysis showed that there were no significant differences between the HFOV and CMV groups in the in-hospital or 30-day mortality rate, incidence of barotrauma, mean ventilation time, and oxygenation index (P>0.05). However, compared with CMV, HFOV increased the PaO/FiOratio by 17%, 24%, and 31% at 24, 48, and 72 hours after treatment respectively, and improved oxygenation in patients.</p><p><b>CONCLUSIONS</b>Although the mortality rate is not reduced by HFOV in children with ARDS, this treatment can result in significant improvement in oxygenation compared with CMV. Further large-sample, multicenter, randomized clinical trials will be required to draw a definitive conclusion.</p>

CT Quantification of Lungs and Airways in Normal Korean Subjects

OBJECTIVE: To measure and compare the quantitative parameters of the lungs and airways in Korean never-smokers and current or former smokers (“ever-smokers”). MATERIALS AND METHODS: Never-smokers (n = 119) and ever-smokers (n = 45) who had normal spirometry and visually normal chest computed tomography (CT) results were retrospectively enrolled in this study. For quantitative CT analyses, the low attenuation area (LAA) of LAA(I-950), LAA(E-856), CT attenuation value at the 15th percentile, mean lung attenuation (MLA), bronchial wall thickness of inner perimeter of a 10 mm diameter airway (Pi10), total lung capacity (TLC(CT)), and functional residual capacity (FRC(CT)) were calculated based on inspiratory and expiratory CT images. To compare the results between groups according to age, sex, and smoking history, independent t test, one way ANOVA, correlation test, and simple and multiple regression analyses were performed. RESULTS: The values of attenuation parameters and volume on inspiratory and expiratory quantitative computed tomography (QCT) were significantly different between males and females (p < 0.001). The MLA and the 15th percentile value on inspiratory QCT were significantly lower in the ever-smoker group than in the never-smoker group (p < 0.05). On expiratory QCT, all lung attenuation parameters were significantly different according to the age range (p < 0.05). Pi10 in ever-smokers was significantly correlated with forced expiratory volume in 1 second/forced vital capacity (r = −0.455, p = 0.003). In simple and multivariate regression analyses, TLC(CT), FRC(CT), and age showed significant associations with lung attenuation (p < 0.05), and only TLC(CT) was significantly associated with inspiratory Pi10. CONCLUSION: In Korean subjects with normal spirometry and visually normal chest CT, there may be significant differences in QCT parameters according to sex, age, and smoking history.

Dual control of the vestibulosympathetic reflex following hypotension in rats

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

Effect of Brace to Osteoporotic Vertebral Fracture: a Meta-Analysis

Brace is one of the most commonly used interventions to manage osteoporotic vertebral fracture. However, its authentic effectiveness remains unclear. The aim of this study was to investigate the efficacy of brace in patients with osteoporotic vertebral fractures. We conducted a literature review and meta-analysis following the guideline and handbook of the Cochrane collaboration. Ten published articles were included in this study and data from 4 randomized controlled trials were analyzed. Low quality evidence proved using Spinomed brace could bring large and significant beneficial effect to patients with sub-acute osteoporotic vertebral fractures. Very low quality evidence proved no significant difference between Spinomed orthosis, rigid brace and soft brace when they were used in patients with acute fractures. Therefore, it might be applicable to recommend middle term use of Spinomed orthosis to patients with subacute fracture. In addition, this study emphasized the need for high quality randomized controlled trials.

Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss / 中国医学科学杂志(英文版)

In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.

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.

Functional Connections of the Vestibulo-spino-adrenal Axis in the Control of Blood Pressure Via the Vestibulosympathetic Reflex in Conscious Rats

Significant evidence supports the role of the vestibular system in the regulation of blood pressure during postural movements. In the present study, the role of the vestibulo-spino-adrenal (VSA) axis in the modulation of blood pressure via the vestibulosympathetic reflex was clarified by immunohistochemical and enzyme immunoassay methods in conscious rats with sinoaortic denervation. Expression of c-Fos protein in the intermediolateral cell column of the middle thoracic spinal regions and blood epinephrine levels were investigated, following microinjection of glutamate receptor agonists or antagonists into the medial vestibular nucleus (MVN) and/or sodium nitroprusside (SNP)-induced hypotension. Both microinjection of glutamate receptor agonists (NMDA and AMPA) into the MVN or rostral ventrolateral medullary nucleus (RVLM) and SNP-induced hypotension led to increased number of c-Fos positive neurons in the intermediolateral cell column of the middle thoracic spinal regions and increased blood epinephrine levels. Pretreatment with microinjection of glutamate receptor antagonists (MK-801 and CNQX) into the MVN or RVLM prevented the increased number of c-Fos positive neurons resulting from SNP-induced hypotension, and reversed the increased blood epinephrine levels. These results indicate that the VSA axis may be a key component of the pathway used by the vestibulosympathetic reflex to maintain blood pressure during postural movements.

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.

Effect of Vestibulosympathetic Reflex and Baroreflex on Expression of pERK in the Nucleus Tractus Solitarius following Acute Hypotension in Conscious Rats

Control of blood pressure is maintained by the interaction between the arterial baroreflex and vestibulosympathetic reflex during postural changes. In this study, the contributions of vestibular receptors and baroreceptors to the maintenance of blood pressure following acute hypotension were compared in terms of phosphorylated extracellular regulated protein kinase (pERK) expression in the nucleus tractus solitaries (NTS). Expression of pERK in the NTS was measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) 5, 10, 20, and 40 min following acute hypotension induced by sodium nitroprusside (SNP) infusion. Expression of pERK increased significantly in the NTS in the control group following SNP infusion, and the expression peaked at 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 in control group. The BL group showed a relatively higher reduction in pERK expression than the SAD group, and the pERK expression in the NTS was localized to the caudal portion of the nuclei in the BL and SAD groups. These results suggest that the vestibular receptors may play a key role in maintaining blood pressure following acute hypotension; thus, the vestibular system may contribute to compensate for orthostatic hypotension.

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.</p><p><b>METHODS</b>Nude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.</p><p><b>CONCLUSIONS</b>Treatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.</p>

Changes of gamma-aminobutyric acid and glycine released in the medial vestibular nucleus following acute hypotension in conscious rats / 生理学报

To understand whether some amino acids in the medial vestibular nucleus (MVN) of conscious rats are involved in the regulation of blood pressure, microdialysis technique and high performance liquid chromatography (HPLC) were used to measure the changes of gamma-aminobutyric acid (GABA) and glycine (Gly) in this central area. Wistar rats (250-350 g) were randomly divided into three experimental groups: the control group with intact labyrinths; the ipsilateral MVN of unilateral labyrinthectomy (UL); contralateral MVN of the UL. Acute hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Unilateral chemical labyrinthectomy was performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. Blood pressure decreased by 30% after SNP injection. In the control group, GABA and Gly release reduced to 43.53%+/-6.58% (P<0.01) and 62.24%+/-7.51% (P<0.01) respectively in the MVN following SNP-induced acute hypotension in conscious rats. In the contralateral MVN of UL, GABA and Gly release also reduced to 45.85%+/-17.27% (P<0.01) and 73.30%+/-3.00% (P<0.01) respectively following SNP-induced acute hypotension in conscious rats. In contrast, in the ipsilateral MVN of UL, GABA and Gly releases were not changed following SNP-induced acute hypotension in conscious rats. These results suggest that the SNP-induced acute hypotension may influence the activity of the neurons in the MVN by the afferent impulses from the peripheral vestibular organ, and that GABA and Gly may be involved in this process.