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961.
Background:
Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:
Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.Results:
The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.Conclusions:
Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis. 相似文献962.
Tang Rining Zhu Dongdong Han Yuchen Wu Min Lyu Linli Ma Kunling Liu Bicheng. 《中华肾脏病杂志》2015,31(5):351-358
Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats. Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ, 35 mg/kg) in spontaneous hypertensive rats (SHR). Diabetic rats were divided into diabetic group and the Irbesartan treated group. The pathological changes were investigated by fluorescence microscope and electron microscope. The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose. The concentration of angiotensin II in the supernatant was detected by radioimmunoassay. Immunofluorescence staining was performed to detect the co - localization of CD31 and FSP1. Results The significant myocardial fibrosis was presented in the diabetic group. Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats. Double staining of HAEC showed co-localization of CD31 and FSP1, which was decreased by the treatment of Irbesartan (P<0.05). When HAEC was exposed to high glucose, it showed some cells acquired spindle-shaped morphology and lost CD31 staining, and FSP1 and α - SMA protein expression levels were markedly upregulated, which attenuated by the treatment of Irbesartan. Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats. 相似文献
963.
Scott W. Mueller Tyree H. Kiser Taylor Morrisette Martin R. Zamora Dennis M. Lyu Jennifer J. Kiser 《Transplant infectious disease》2021,23(1):e13464
Respiratory syncytial virus (RSV) is responsible for significant morbidity and mortality in the lung transplant population. Oral and aerosolized ribavirin may improve outcomes in lung transplant patients with RSV; however, data relating ribavirin concentrations in plasma and intracellular ribavirin triphosphate (iRTP) concentrations in blood and bronchoalveolar lavage (BAL) fluid cells with efficacy and safety are lacking. We describe ribavirin and iRTP concentrations within various compartments in two adult lung transplant recipients with RSV who were sampled throughout successful treatment courses with oral and inhaled ribavirin. In patient 1, iRTP BAL concentrations decreased by 45% over 3 days after changing inhaled ribavirin to oral (6.32 to 3.43 pmol/106 cells). In patient 2, iRTP BAL concentrations were 103 pmol/106 cells after 5 days of oral followed by 5 days of inhaled ribavirin. Further study is needed to describe ribavirin pharmacokinetics in the respiratory compartment to inform clinical use of ribavirin for respiratory viruses. 相似文献
964.
965.
Xu Wangshu Zhang Wenqun Cui Lili Shi Lei Zhu Bin Lyu Tina-Jie Ma Wenping 《Metabolic brain disease》2022,37(4):1207-1219
Metabolic Brain Disease - Developmental and Epileptic Encephalopathy (DEE) is a group of disorders affecting children at early stages of infancy, which is characterized by frequent seizures,... 相似文献
966.
目的探讨对侧抑制性重复经颅磁刺激(rTMS)联合运动想象(MI)对脑卒中偏瘫患者肢体功能的康复效果。 方法选取廊坊市第四人民医院神经内科自2017年1月至2019年10月收治的108例脑卒中偏瘫患者为研究对象,按照随机数字表法将其分为常规组、MI组和联合组,每组36例。常规组接受常规药物治疗及康复治疗,MI组在常规组治疗基础上进行MI训练,联合组在MI组基础上进行对侧抑制性rTMS治疗;3组疗程均为4周。比较3组患者的临床疗效、治疗前后患侧运动诱发电位潜伏期(MEP-CL)、中枢运动传导时间(CMCT)、平衡量表(BBS)评分、起立-行走计时测试(TUGT)时间、修订版跌倒效能量表(MFES)评分、简化Fugl-Meyer评测法(FMA)评分、手部精细动作评估量表(MAS)评分、改良Barthel量表(MBI)评分。 结果常规组、MI组、联合组治疗4周后总有效率分别为50.0%、77.8%、94.1%,3组患者的临床疗效比较差异有统计学意义(P<0.05)。3组患者的治疗前MEP-CL、CMCT、TUGT时间及BBS、MFES、FMA、手部精细动作MAS、MBI评分比较,差异无统计学意义(P>0.05)。治疗4周后,3组患者的MEP-CL、CMCT、TUGT时间缩短,BBS、MFES、FMA、手部精细动作MAS、MBI评分增高(P<0.05);改善程度:联合组>MI组>常规组,差异具有统计学意义(P<0.05)。 结论对侧抑制性rTMS联合MI有利于脑卒中偏瘫患者的肢体功能康复,且能明显提高患者的生命质量。 相似文献
967.
Xian-Yinan Pei Dong-Chuan Mo Shu-Shen Lyu Jian-Hui Zhang Yuan-Xiang Fu 《RSC advances》2018,8(50):28518
MnO micrometer particles with a two-stage structure (composed of mass nanoparticles) were produced via a one-step hydrothermal method using histidine and potassium permanganate (KMnO4) as reagents, with subsequent calcination in a nitrogen (N2) atmosphere. When the MnO micrometer particles were utilized in lithium-ion batteries (LIBs) as anode materials, the electrode showed a high reversible specific capacity of 747 mA h g−1 at 100 mA g−1 after 100 cycles, meanwhile, the electrode presented excellent rate capability at various current densities from 100 to 2000 mA g−1 (∼203 mA h g−1 at 2000 mA g−1). This study developed a new approach to prepare two-stage structure micrometer MnO particles and the sample can be a promising anode material for lithium-ion batteries.MnO micrometer particles with a two-stage structure (composed of mass nanoparticles) were produced via a one-step hydrothermal method using histidine and potassium permanganate (KMnO4) as reagents, with subsequent calcination in a nitrogen (N2) atmosphere. 相似文献
968.
Identification and characterization of in vitro and in vivo metabolites of steroidal alkaloid veratramine 下载免费PDF全文
Chunming Lyu Wenbin Zhou Yufeng Zhang Shen Zhang Fang Kou Zhong Zuo 《Biopharmaceutics & drug disposition》2015,36(5):308-324
Veratramine, a steroidal alkaloid originating from Veratrum nigrum L., has demonstrated distinct anti‐tumor and anti‐hypertension effects, however, its metabolism has rarely been explored. The objective of the current study was to provide a comprehensive investigation of its metabolic pathways. The in vitro metabolic profiles of veratramine were evaluated by incubating it with liver microsomes and cytosols. The in vivo metabolic profiles in plasma, bile, urine and feces were monitored by UPLC‐MS/MS after oral (20 mg/kg) and i.v. (50 µg/kg) administration in rats. Meanwhile, related P450s inhibitors and recombinant P450s and SULTs were used to identify the isozymes responsible for its metabolism. Eleven metabolites of veratramine, including seven hydroxylated, two sulfated and two glucuronidated metabolites, were characterized. Unlike most alkaloids, the major reactive sites of veratramine were on ring A and B instead of on the amine moiety. CYP2D6 was the major isozyme mediating hydroxylation, and substrate inhibition was observed with a Vmax, Ki and Clint of 2.05 ± 0.53 nmol/min/mg, 33.08 ± 10.13 µ m and 13.58 ± 1.27 µL/min/mg. SULT2A1, with Km, Vmax and Clint values of 19.37 ± 0.87 µ m , 1.51 ± 0.02 nmol/min/mg and 78.19 ± 8.57 µL/min/mg, was identified as the major isozyme contributing to its sulfation. In conclusion, CYP2D6 and SULT2A1 mediating hydroxylation and sulfation were identified as the major biotransformation for veratramine. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
969.
目的探究真实世界中表皮生长因子受体(EGFR)敏感突变的晚期NSCLC患者使用吉非替尼、厄洛替尼、埃克替尼一线治疗进展后T790M突变的分布特征。 方法2017年6月至2019年6月期间557例肺癌患者,145例经病理组织学或细胞学确诊为晚期非小细胞肺癌(NSCLC)且具有EGFR敏感突变的患者,给予吉非替尼、厄洛替尼、埃克替尼一线治疗。随访进展后,采集其外周血10 ml,利用Super-ARMS法检测T790M突变。通过χ2检验,Kaplan-Meier分析,回顾性分析晚期NSCLC患者接受吉非替尼、厄洛替尼、埃克替尼一线治疗后T790M突变患者的分布特征。 结果回顾性分析的145例患者,56例一线接受吉非替尼治疗,16例接受厄洛替尼治疗,73例接受埃克替尼治疗。Super-ARMS检测结果显示,一代EGFR-TKIs治疗进展后T790M突变的总体发生率为40% (58/145),其中吉非替尼组41.07% (23/56)、厄洛替尼组31.25%(5/16)、埃克替尼组41.10% (30/73)。三组患者之间T790M突变的发生率无统计学差异。但是,肺腺癌(P=0.0001)及初始EGFR突变为19del(P=0.0014)的患者更易发生T790M突变。T790M阳性患者中,吉非替尼、厄洛替尼、埃克替尼的中位PFS(mPFS)分别为:11个月、18个月和12个月,组间无统计学差异。TKI治疗1年、2年后T790M突变率及T790M阳性人群的中位PFS均无统计学差异。 结论真实世界中吉非替尼、厄洛替尼、埃克替尼一线治疗晚期NSCLC耐药进展后,其血检标本T790M的突变发生率无统计学差异。但是,初始突变为19del的患者相较于L858R突变的患者更容易发生T790M突变。这也进一步预示着NSCLC患者精细化管理的必要性。 相似文献
970.
Huixian Li Wanhong Lu Ani Wang Hongli Jiang Jun Lyu 《Journal of diabetes investigation.》2021,12(3):346-356
Aims/IntroductionType 2 diabetes mellitus has been a leading cause of chronic kidney disease (CKD), with a heterogeneous distribution worldwide. Optimal healthcare planning requires an understanding of how the burden of CKD as a result of type 2 diabetes mellitus has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical and behavioral factors in these changes.Materials and MethodsWe used the Global Burden of Disease data from 1990 to 2017 at the global, regional and national levels to investigate changes in the incidence, death and disability‐adjusted life years of CKD as a result of type 2 diabetes mellitus, incorporating both epidemiological research and risk factor monitoring.ResultsThe incident cases of CKD as a result of type 2 diabetes mellitus worldwide in 2017 had increased by 74% compared with 1990; total disability‐adjusted life years had increased by 113%, mainly attributable to population expansion and demographic transition. The Sociodemographic Index was significantly and negatively correlated with overall CKD as a result of type 2 diabetes mellitus burden. However, in 82 countries and territories, the burden was not alleviated in parallel with socioeconomic development.ConclusionsCKD as a result of type 2 diabetes mellitus has been the main contributor to the increasing burden of CKD over the past several decades. We suggest a more pragmatic approach focusing on early diagnosis, primary care and adequate follow up to reduce mortality and the long‐term burden in low‐to‐middle Sociodemographic Index regions. Interventions should address high systolic blood pressure, as well as overweight and obesity problems, especially in high‐income regions. 相似文献