Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two-kidney one-clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT 1 ) receptors in mediating the CSAR was determined. Under urethane and α-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with shamoperated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1-containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT 1 receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT 1 receptors are involved in the enhanced CSAR in 2K1C rats.

Sympathetic activity is enhanced in hypertension, which contributes to the pathogenesis of hypertension and progression of organ damage. The cardiac sympathetic afferent reflex (CSAR) is enhanced in renovascular hypertension and involved in the sympathetic activation. The present study was designed to investigate whether angiotensin II (Ang II) and Ang II type 1 (AT 1 ) receptors in paraventricular nucleus (PVN) contribute to the enhanced CSAR and sympathetic outflow in experimental renovascular hypertensive rats. Hypertension was induced by the twokidney one-clip (2K1C) method. The normotensive rats underwent sham operation (Sham). Acute experimentation was carried out at the end of the 4th week. Under urethane and α-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in rats with sino-aortic denervation and cervical vagotomy. The AT 1 receptor expression was determined with Western blot. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. The AT 1 receptor expression in the PVN was increased, and Ang II in the PVN augmented the enhanced CSAR and RSNA in 2K1C rats. The effects of Ang II were abolished by pretreatment with the AT 1 receptor antagonist, losartan, in 2K1C rats. Losartan in the PVN normalized the enhanced CSAR and decreased the RSNA and MAP in 2K1C rats. These results indicate that the increased activity of AT 1 receptors in the PVN contributes to the enhanced CSAR and excessive sympathetic activation in renovascular hypertensive rats.

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INTRODUCTIONOsteosarcoma is the most prevalent malignant bone tumor in children and adolescents. An overall annual prevalence of 0.2-3 cases per 100,000 population has been reported. 1 Despite the rarity of osteosarcoma, it remains one of the deadliest cancers during the pubertal growth spurt. Lung metastases have been reported to be one of the challenging factors associated with a poor prognosis. 2 Approximately 20% of osteosarcoma patients present with metastatic disease at the time of the initial diagnosis. The most prevalent metastatic type is lung metastasis, which occurs in more than 80% of the cases. 3,4 Despite the development of novel treatments for osteosarcoma, 30-40% of these patients still relapse and the long-term post-relapse survival among these individuals has been reported to be less than 20%. 5,6 Undoubtedly, osteosarcoma patients can benefit from early diagnosis and treatment of metastases. Thus, a reasonable degree of lung metastasis screening for osteosarcoma patients at diagnosis is important. Male sex and the site involved (femur and tibia) were confirmed to be associate with greater occurrence of metastasis in a Mexican clinical trial. 7 The primary tumor size was reported to be a risk factor for lung metastasis among patients with osteosarcoma. 8,9 Currently, radiography is one of the most widely applied clinical screening strategies.However, radiography barely captures metastases until they physically form. Therefore, studies looking into the risk factors for lung metastasis occurrence among patients with osteosarcoma are warranted. ABSTRACT BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents. Lung metastases are associated with poor prognosis. OBJECTIVE: The aim here was to explore the prevalence of and risk and prognostic factors for lung metastases in high-grade osteosarcoma patients. DESIGN AND SETTING: Retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database in the United States. METHODS: Data on 1,408 high-grade osteosarcoma patients registered in the SEER database between 2010 and 2015 were extracted. From these, all patients with high-grade osteosarcoma and initial lung metastasis were selected for analysis on risk and prognostic factors for lung metastases. Overall survival was estimated. RESULTS: There were 238 patients (16.90%) with lung metastases at diagnosis. Axial location, tumor size > 10 cm (odds ratio, OR 3.19; 95% confidence interval, CI: 1.58-6.45), higher N stage (OR 4.84; 95% CI: 1.94-12.13) and presence of bone metastases (OR 8.73; 95% CI: 4.37-17.48) or brain metastases (OR 25.63; 95% CI: 1.55-422.86) were significantly associated with lung metastases. Younger age and surgical treatment (hazard ratio, HR 0.46; 95% CI: 0.30-0.71) favored survival. Median survival was prolonged through primary tumor surgery. CONCLUSIONS:The factors revealed here may guide lung metastasis screening and prophylactic treatment for osteosarcoma patients. A primary tumor in an axial location, greater p...

The purpose of this study was to determine whether the long-term administration of tempol attenuates postinfarct ventricular dysfunction and sympathetic activity in rats. Myocardial infarction (MI) was induced by left descending coronary artery ligation. Tempol was orally administered in drinking water (2 mmol/L), which was initiated 4 h after infarction and continued for 6 weeks. Tempol prevented not only the increases in left ventricular end-diastolic pressure and volume but also the decreases in ejection fraction and peak velocities of contraction in MI rats. The treatment normalized the increased renal sympathetic nerve activity (RSNA) and plasma norepinephrine level, as well as the enhanced cardiac sympathetic afferent reflex (CSAR; an excitatory cardiovascular reflex partially contributing to the sympathetic activation in chronic heart failure) and the RSNA responses to microinjection of angiotensin II into paraventricular nucleus in MI rats. Furthermore, tempol prevented the increased AT(1) receptor protein expression and superoxide anion level in both paraventricular nucleus and rostral ventrolateral medulla in MI rats. In conclusion, long-term administration of tempol attenuates ventricular dysfunction and normalizes sympathetic neural control in MI rats. The normalization of the CSAR, levels of superoxide anions and AT(1) receptor expression, and the response to angiotensin II in the paraventricular nucleus and rostral ventrolateral medulla may partially contribute to the beneficial effects of tempol on central sympathetic control.

BackgroundThe purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer.Patients and methodsThis study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan–Meier method and the survival differences were tested by the log-rank test.ResultsA total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89–4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001).ConclusionDifferent lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5445-3) contains supplementary material, which is available to authorized users.

Purpose Using the Surveillance, Epidemiology, and End Results database (SEER) to assess the incidence and risk factors of morbidity and prognosis for bone metastases in initial metastatic prostate cancer. Patients and methods The records of 249,331 prostate cancer patients in the SEER database, diagnosed between 2010 and 2014, were obtained were obtained to investigate the risk factors for developing bone metastasis, and the records of 9925 of them who registered before 2013 were retrieved (with at least 1 year follow up) to explore the prognostic factors for bone metastasis. Multivariate logistic and Cox regression were used to identify risk factors and prognostic factors for bone metastases, respectively. Results In total, 12,794 patients (5.1%) were diagnosed with bone metastases at the initial diagnosis. Older age, unmarried status, lymph node metastasis, poor tumor differentiation grade (Gleason grade), metastases at lung, brain, and liver were all positively associated with risk for the morbidity and prognosis of bone metastasis in prostate cancer. Black race and higher T stage were positively associated with bone metastasis development; however, they were not associated with a prognosis of bone metastasis. Conclusion The incidence of bone metastasis in prostate cancer was approximately 5% with poor survival. The prostate cancer has homogeneous and heterogeneous risk factors for incidence and prognosis of bone metastasis, which may provide potential guidelines for the screening and preventive treatment for the bone metastasis of prostate cancer.

Background Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis. Methods Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed. Results A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3–20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726–0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730–0.762). Conclusion A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.