CRH receptor type 1 mediates continual hypoxia-induced changes of immunoreactive prolactin and prolactin mRNA expression in rat pituitary

We have reported that, in rats, hypoxia (10.8% O2) stimulates prolactin (PRL) release from the pituitary. This study is designed to compare the response of pituitary PRL to acute hypoxia (AH), continual hypoxia (CH), intermittent hypoxia (IH), cold, and restraint, individually and combined with hypoxia. This study also investigates the involvement of the corticotropin-releasing hormone receptor 1 (CRH R1) in the hypoxia-induced PRL response. Hypoxia was induced by exposing the rats to high altitudes of 2 km (16.0% O2) or 5 km (10.8% O2). The PRL levels in the pituitary (iPRL) and in plasma (pPRL) were measured by immunocytochemistry and RIA assay, respectively. The acute hypoxia of 5 km for 2-24 h caused a biphasic change (early decrease and late increase) of PRL. Both CH and IH at 2 or 5 km for 1-5 days markedly increased pPRL but decreased iPRL. Continual severe hypoxia (10.8% O2) for periods of 10, 15, and 25 days significantly enhanced pPRL but this effect was less marked at the lower altitude (16.0% O2) and did not occur during intermittent hypoxia (at both altitudes). The increased pPRL was significantly enhanced by restraint, restraint + hypoxia, hypoxia, and cold + hypoxia exposure. Treatment with a CRH R1 antagonist (CP-154,526) reversed hypoxia-decreased immunoreactive PRL and upregulated PRLmRNA in the pituitary. The data suggest that both CH and IH can stimulate rat PRL release in a time-course- and intensity-dependent manner. However, compared to the relatively low CH-induced response, restraint induced a more powerful response than either cold or hypoxia alone. CRH R1 mediates PRL secretion and PRL mRNA expression in the pituitary under hypoxic exposure. Hypoxia-enhanced PRL response over the lifespan may play a significant role in adaptation to an extreme environment.     

益生菌对维持性血液透析慢性肾脏病患者肠道菌群失调的影响

目的探究益生菌对维持性血液透析慢性肾脏病患者肠道菌群失调的影响,为此类患者的治疗提供参考。方法选取2017年4月到2019年4月我院收治的78例维持性血液透析慢性肾病患者,按照随机数字法分为观察组和对照组各39例。对照组患者给予常规治疗,观察组患者给予常规治疗联合益生菌。检测两组患者肠道菌群变化,同时检测血清炎性因子(IL6、TNFα、CRP)、肠道屏障功能(D乳酸、内毒素)及肾功能指标[肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen,BUN)]水平。结果治疗后两组患者Scr、BUN水平均下降(均P<0.05),观察组与对照组比较有减少趋势,但差异无统计学意义(均P>0.05)。治疗后两组患者肠道双歧杆菌、乳杆菌数量均增加,大肠埃希菌、肠球菌数量均下降,且观察组患者改善情况优于对照组,差异有统计学意义(t=4.226、9.634、6.157、2.739,P<0.001、<0.001、<0.001、=0.008)。治疗后两组患者D乳酸、内毒素水平均降低,且观察组低于对照组,差异有统计学意义(t=2.856、3.125,P=0.007、0.003)。治疗后两组患者血清IL6、TNFα、CRP水平均下降,且观察组下降幅度更大,差异具有统计学意义(t=3.124、4.025、8.024,P=0.007、<0.001、<0.001)。结论益生菌对维持性血液透析慢性肾脏病患者肠道菌群失衡、肠道屏障功能和微炎症状态均具有改善作用,可为该类患者临床治疗提供一定参考。     

黄葵胶囊联合组合型人工肾对糖尿病肾病维持性血液透析患者炎性因子、氧化应激及生活质量的影响

摘要 目的：探讨黄葵胶囊联合组合型人工肾对糖尿病肾病维持性血液透析患者炎性因子、氧化应激及生活质量的影响。方法：选取2018年10月~2019年9月我院收治的120例终末期糖尿病肾病维持性血液透析患者,将其按照随机数字表法分为观察组和对照组,各60例。两组患者均给予基础治疗,对照组采取组合型人工肾治疗。观察组在对照组基础上给予黄葵胶囊治疗。比较两组治疗3个月后的肾功能指标、炎性因子水平、氧化应激指标水平及生活质量,并统计不良反应发生情况。结果：治疗3个月后,两组血清尿素氮(BUN)、血清肌酐(Scr)、白蛋白排泄率(UAER)、超敏-C反应蛋白(hs-CRP)、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、晚期氧化蛋白产物（AOPP）、丙二醛（MDA）水平低于治疗前,且观察组低于对照组（P＜0.05）。两组过氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）水平及SF-36各维度评分均高于治疗前,且观察组高于对照组（P＜0.05）。两组不良反应发生率比较无明显差异（P＞0.05）。结论：黄葵胶囊联合组合型人工肾治疗终末期糖尿病肾病可有效减轻患者氧化应激及炎症反应,改善患者肾功能及生活质量,安全性高,具有较好的临床应用价值。     

Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy

These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi.     

Effects of Hemodialysis,Dialyser Type and Iron Infusion on Oxidative Stress in Uremic Patients

Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde–deoxyguanosine-adducts (M₁dG) with an immunoslot blot technique.

HD-patients (n=21) showed a significant increase of total DNA damage (p<10^-12), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M₁dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005).

Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.     

高通量血液透析对糖尿病肾病血液透析患者心脏功能及结构的影响及预后的影响因素分析

摘要 目的：探讨高通量血液透析对糖尿病肾病（DN）血液透析患者心脏功能及结构的影响,并分析预后的影响因素。方法：选取2017年5月~2018年11月期间我院收治的DN血液透析患者（n=172）,上述DN血液透析患者中普通透析治疗者60例（普通透析组）、高通量血液透析治疗者112例（高通量透析组）。普通透析组采用低通量透析治疗,高通量透析组采用高通量透析治疗,比较两组患者心脏功能及结构以及预后情况,采用单因素、多因素Logistic回归分析预后的影响因素。结果：高通量透析组治疗6个月后左心房内径（LAD）、左心室舒张末内径（LVDd）、左心室心肌重量指数（LVMI）低于治疗前和普通透析组（P<0.05）,高通量透析组治疗6个月后左心室射血分数( LVEF )高于治疗前和普通透析组（P<0.05）。高通量透析组的生存率高于普通透析组（P<0.05）。存活组年龄、上机前舒张压、上机前收缩压、血磷、全段甲状旁腺激素（iPTH）均低于死亡组（P<0.05）,存活组透析频率、白蛋白、血红蛋白均高于死亡组（P<0.05）,两组性别、血钙比较无差异（P>0.05）。多因素Logistic回归分析结果显示,上机前舒张压高、上机前收缩压高、血磷高、iPTH高、透析频率少、白蛋白低、血红蛋白低均是DN血液透析患者死亡的危险因素（P<0.05）。结论：高通量血液透析能减轻DN患者血液透析所引起的心脏功能及结构损伤,改善患者预后。影响DN血液透析患者预后的因素较多,其中上机前舒张压、上机前收缩压、血磷、iPTH越高,白蛋白、血红蛋白越低,透析频率越少,患者的死亡风险越大。     

高通量血液透析联合肾衰宁颗粒对尿毒症患者钙磷代谢、炎症反应以及营养状况的影响

摘要 目的：探讨高通量血液透析（HFHD）联合肾衰宁颗粒对尿毒症患者钙磷代谢、炎症反应以及营养状况的影响。方法：选取2017年1月~2019年10月在我院接受血液透析治疗的尿毒症患者114例作为研究对象,按随机数字表法分成对照组和观察组,每组各57例,对照组给予HFHD,观察组在对照组基础上口服肾衰宁颗粒。两组均治疗3个月。比较两组患者治疗前后肾功能指标,包括尿素氮（BUN）、血肌酐（Scr）、肾小球滤过率（GFR）;钙磷代谢相关指标血清钙、血清磷、甲状旁腺激素（PTH）;炎症反应指标,包括降钙素原（PCT）、C反应蛋白（CRP）、白细胞介素-6（IL-6）;营养状况指标,包括白蛋白（ALB）、血红蛋白（Hb）、血清总蛋白（TP）。结果：治疗后两组患者BUN、Scr、GFR、血清磷、PTH、PCT、CRP、IL-6较治疗前降低,血清钙、ALB、Hb、TP较治疗前升高,观察组患者BUN、Scr、GFR、血清磷、PTH、PCT、CRP、IL-6低于对照组,血清钙、ALB、Hb、TP高于对照组,差异均有统计学意义（P<0.05）。结论：HFHD联合肾衰宁颗粒治疗尿毒症,可有效改善患者的钙磷代谢和肾功能,改善机体炎症状态及营养状况。     

维持性血液透析患者腹主动脉钙化与左室重量指数、预后的关系及其影响因素分析

摘要 目的：研究维持性血液透析（MHD）患者腹主动脉钙化与左室重量指数（LVMI）、预后的关系及其影响因素。方法：将医院从2016年5月到2018年6月收治的182例MHD患者纳入研究。将所有患者按照腹主动脉钙化评分分为钙化组（腹主动脉钙化评分>0分）145例和非钙化组（腹主动脉钙化评分=0分）37例。分析比较两组LVMI、临床基线资料以及实验室检查指标水平的差异。采用多因素Logistic回归分析明确MHD患者腹主动脉钙化的影响因素。结果：钙化组LVMI明显高于非钙化组,差异有统计学意义（P＜0.05）。钙化组全因死亡率、心血管死亡率均高于非钙化组（P＜0.05）;且经Kaplan-Meier生存曲线分析发现：钙化组患者全因死亡累积生存率以及心血管死亡累积生存率均明显低于非钙化组（P＜0.05）。钙化组年龄、透析龄以及血磷、全段甲状旁腺激素水平均高于非钙化组,而25羟维生素D3水平低于非钙化组（P＜0.05）。经多因素Logistic回归分析发现：年龄、透析龄、血磷、全段甲状旁腺激素及LVMI均是MHD患者腹主动脉钙化的独立危险因素,而25羟维生素D3是MHD患者腹主动脉钙化的保护因素（P＜0.05）。结论：MHD患者腹主动脉钙化与LVMI、预后密切相关,且年龄、透析龄、以及血磷、全段甲状旁腺激素、25羟维生素D3、LVMI均是MHD患者腹主动脉钙化的影响因素。     

加兰他敏对间歇性低氧引起的认知损害的预防作用

目的：探究加兰他敏对间歇性低氧引起的认知损伤是否有保护作用,从而说明其对睡眠呼吸暂停综合症引起的认知损害是否有预防作用。方法：建立间歇低氧大鼠模型,行水迷宫试验检测行为功能变化,免疫组化检测海马神经元及胶质细胞数目的变化。结果：加兰他敏与间歇低氧模型纽相比,行水迷宫的平均逃避潜伏期缩短,游泳总距离减少;免疫组化的结果海马神经元的数目有所增加,胶质细胞的数目减少。结论：加兰他敏对间歇性低氧引起的认知损伤有明显的改善作用,可能与减少神经元的丢失及减少胶质细胞的再生有关。所以对于诊断了睡眠呼吸暂停综合征（ASA）的患者,如果同时合并其他痴呆的易感因素,可预防性应用加兰他敏.