Protective Cellular Mechanism of Estrogen Against Kidney Stone Formation: A Proteomics Approach and Functional Validation

Females have less incidence/prevalence of kidney stone disease than males. Estrogen thus may serve as the protective factor but with unclear mechanism. This study explores cellular mechanism underlying such stone preventive mechanism of estrogen. Madin darby canine kidney (MDCK) renal tubular cells are incubated with or without 20 nm 17β‐estradiol for 7 days. Comparative proteomics reveals 58 differentially expressed proteins in estrogen‐treated versus control cells that are successfully identified by nanoLC–ESI–Q‐TOF‐MS/MS. Interestingly, these altered proteins are involved mainly in “binding and receptor,” “metabolic process,” and “migration and healing” networks. Functional investigations demonstrate reduction of calcium oxalate (CaOx) crystal‐binding capability of the estrogen‐treated cells consistent with the decreased levels of annexin A1 and α‐enolase (the known CaOx crystal‐binding receptors) on the cell surface. High‐calcium and high‐oxalate challenge initially enhances surface expression of annexin A1 and α‐enolase, respectively, both of which return to their basal levels by estrogen. Additionally, estrogen reduces intracellular ATP level and promotes cell migration and tissue healing. Taken together, estrogen causes changes in cellular proteome of renal tubular cells that lead to decreased surface expression of CaOx crystal receptors, reduced intracellular metabolism, and enhanced cell proliferation and tissue healing, all of which may contribute, at least in part, to stone prevention.     

健脾安肠汤联合匹维溴胺治疗肠易激综合征的临床疗效及对血清5-HT、CGRP、SP、VIP水平的影响

目的:探讨健脾安肠汤联合匹维溴胺治疗肠易激综合征的临床疗效及对血清5-羟色胺(5-HT)、降钙素基因相关肽(CGRP)、结肠黏膜P物质(SP)、血管活性肠态(VIP)水平的影响。方法:选择2017年1月至2017年12月本院接诊的98例肠易激综合征患者作为研究对象,按随机数表法分为观察组(n=45)和对照组(n=53),对照组单纯采用匹维溴胺进行治疗,观察组在此基础上联合健脾安肠汤进行治疗。比较两组患者的临床疗效及治疗前后胃肠症状改善情况、血清5-HT、CGRP、SP、VIP水平、炎性因子水平、焦虑(SAS)、抑郁(SDS)评分的变化。结果:治疗后,观察组总有效率(93.33%)心脏高于对照组(71.70%,P0.05);观察组患者恶心呕吐、腹痛腹泻、排便次数及大便性质症状评分,血清5-HT、CGRP、SP、VIP、IL-8、IL-6水平、焦虑及抑郁评分均明显低于对照组(均P0.05),而血清IL-10水平显著高于对照组(P0.05)。结论:健脾安肠汤联合匹维溴胺治疗肠易激综合征的临床效果显著优于单纯采用匹维溴胺治疗,可有效调节机体胃肠激素分泌和临床症状,提高患者患者生活质量。     

甲状腺术中喉返神经显露对暂时性喉返神经损伤发生率的影响

目的:探究甲状腺术中喉返神经显露对暂时性喉返神经损伤发生率的影响。方法:选择我院2016年10月-2018年10月收治的行甲状腺切除术的115例患者为研究对象,按照其入院顺序经随机数字表法分为两组,两组患者均行常规甲状腺切除术。其中,对照组58例患者未显露喉返神经;研究组57例患者常规显露喉返神经,记录并比较两组患者的手术时间、术中出血量、术后引流量、切口长度和住院时间等围术期手术指标,术后1d、4d、7d的甲状旁腺激素(PTH)水平、钙离子(Ca2+)水平,术后暂时性喉返神经损伤、术后声音嘶哑、低钙血症等并发症的发生情况。结果:研究组患者的手术时间、术中出血量、术后引流量均短于(少于)对照组(P0.05),但两组患者的切口长度和住院时间无显著性差异(P0.05);研究组患者术后1d、4d、7d的血清PTH、Ca2+水平均高于对照组(P0.05),暂时性喉返神经损伤、术后声音嘶哑、低钙血症发生率均低于对照组(P0.05)。结论:甲状腺术中喉返神经显露可有效预防暂时性喉返神经和甲状腺功能的损伤,降低术后并发症的发生率,且患者的围术期指标均显著改善。     

血清B型脑钠肽、糖类抗原125及甲状腺激素水平与慢性心力衰竭患者心功能的相关性研究

目的:探究慢性心力衰竭(CHF)患者血清B型脑钠肽(BNP)、糖类抗原125(CA125)和甲状腺激素(TH)水平与心功能的相关性。方法:选取2015年12月-2017年12月我院收治的120例CHF患者作为本次研究的对象,患者的心功能分级状况为纽约心脏病协会(NYHA)Ⅰ/Ⅱ级51例、NYHAⅢ级39例、NYHAⅣ级30例,另选取同期在我院接受体检的健康志愿者40例作为对照组。检测所有研究对象的血清BNP、CA125和TH水平,并分析其与患者左心室射血分数(LVEF)、左室舒张末内径(LVEDD)间的关系。结果:不同心功能分级患者血清BNP、CA125水平均显著高于对照组,且BNP、CA125水平随NYHA分级升高而逐渐升高(P0.05)。NYHAⅢ级、NYHAⅣ级患者的血清T3水平显著低于对照组,且T3水平随NYHA分级升高而逐渐降低,各组间比较差异有统计学意义(P0.05)。Pearson分析结果显示,CHF患者血清BNP、CA125水平与LVEF呈负相关(P0.05),而与LVEDD呈正相关(P0.05);血清T3水平与LVEF呈正相关(P0.05),与LVEDD呈负相关(P0.05)。结论:CHF患者血清BNP、CA125及T3水平均与心功能存在密切联系,三者联合检测对CHF的临床诊断与病情判断有重要价值。     

Plasticity for colour adaptation in vertebrates explained by the evolution of the genes pomc,pmch and pmchl

Different camouflages work best with some background matching colour. Our understanding of the evolution of skin colour is based mainly on the genetics of pigmentation (“background matching”), with little known about the evolution of the neuroendocrine systems that facilitate “background adaptation” through colour phenotypic plasticity. To address the latter, we studied the evolution in vertebrates of three genes, pomc, pmch and pmchl, that code for α‐MSH and two melanin‐concentrating hormones (MCH and MCHL). These hormones induce either dispersion/aggregation or the synthesis of pigments. We find that α‐MSH is highly conserved during evolution, as is its role in dispersing/synthesizing pigments. Also conserved is the three‐exon pmch gene that encodes MCH, which participates in feeding behaviours. In contrast, pmchl (known previously as pmch), is a teleost‐specific intron‐less gene. Our data indicate that in zebrafish, pmchl‐expressing neurons extend axons to the pituitary, supportive of an MCHL hormonal role, whereas zebrafish and Xenopus pmch+ neurons send axons dorsally in the brain. The evolution of these genes and acquisition of hormonal status for MCHL explain different mechanisms used by vertebrates to background‐adapt.     

Delineation of critical amino acids in activation function 1 of progesterone receptor for recruitment of transcription coregulators

The activation functions AF1 and AF2 of nuclear receptors mediate the recruitment of coregulators in gene regulation. AF1 is mapped to the highly variable and intrinsically unstructured N terminal domain and AF2 lies in the conserved ligand binding domain. The unstructured nature of AF1 offers structural plasticity and hence functional versatility in gene regulation. However, little is known about the key functional residues of AF1 that mediates its interaction with coregulators. This study focuses on the progesterone receptor (PR) and reports the identification of K464, K481 and R492 (KKR) as the key functional residues of PR AF1. The KKR are monomethylated and function cooperatively. The combined mutations of KKR to QQQ render PR isoform B (PRB) hyperactive, whereas KKR to FFF mutations abolishes as much as 80% of PR activity. Furthermore, the hyperactive QQQ mutation rescues the loss of PR activity due to E911A mutation in AF2. The study also finds that the magnitudes of the mutational effect differ in different cell types as a result of differential effects on the functional interaction with coregulators. Furthermore, KKR provides the interface for AF1 to physically interact with p300 and SRC-1, and with AF2 at E911. Intriguingly, the inactive FFF mutant interacts strikingly stronger with both SRC-1 and AF2 than wt PRB. We propose a tripartite model to describe the dynamic interactions between AF1, AF2 and SRC-1 with KKR of AF1 and E911 of AF2 as the interface. An overly stable interaction would hamper the dynamics of disassembly of the receptor complex.     

樟叶越桔组培苗生根和移栽技术研究

为解决樟叶越桔(Vaccinium dunalianum)组培苗生根质量不佳、移栽成活率低的问题,该研究以樟叶越桔继代苗为材料,采用单因子试验从激素类型及浓度、培养基类型和蔗糖质量浓度对其生根的适宜条件进行筛选,进一步研究了不同基质配比对樟叶越桔移栽苗存活率的影响。结果表明:激素类型和浓度、培养基类型对樟叶越桔生根率的影响最大,其次为蔗糖质量浓度;最适合樟叶越桔生根的激素及浓度为IBA2.0 mg·L~(-1)、基本培养基类型为1/4MS、蔗糖质量浓度为15 g·L~(-1),樟叶越桔组培苗最佳生根培养基为1/4MS+IBA 2.0 mg·L~(-1)+活性炭0.1 g·L~(-1)+蔗糖15 g·L~(-1),生根率达100%,平均生根数为每株7.67条;根系呈辐射状、基部无愈伤组织,组培苗生长健壮、叶色浓绿;樟叶越桔组培苗移栽时以全腐殖土基质为佳,成活率为83.7%,植株叶片舒展,生长状况良好。该研究建立的优化体系有效地提高了樟叶越桔组培生根苗的生根率和生根质量,解决了后期移栽成活困难的问题,为优良的樟叶越桔植株规模化生产提供了科学依据和技术支持。     

藏药多刺绿绒蒿种子萌发特性研究

多刺绿绒蒿(Meconopsis horridula)为罂粟科绿绒蒿属一年生草本植物,是一种极具观赏价值和药用价值的高山植物,目前处于濒危状态,因此研究多刺绿绒蒿种子的萌发特性对其种子育苗及人工栽培具有重要意义。为了提高多刺绿绒蒿的种子发芽率,该研究以多刺绿绒蒿的种子为材料,分析了不同消毒剂、浸种时间、温度和外源植物激素对种子萌发特性的影响。结果表明:(1)最适消毒方法为75%乙醇1 min+3%H2O25 min,最适浸种时间为24 h,最适温度和光照条件为20℃/10℃(光照12 h/黑暗12 h),用无菌水浸种后的种子发芽率为49.67%。(2) GA_3100～600 mg·L~(-1)和NAA 5～30 mg·L~(-1)可以提高种子的发芽率、发芽势和发芽指数,缩短发芽启动时间和发芽持续时间,对种子的萌发有促进作用。(3) 6-BA 5 mg·L~(-1)和10 mg·L~(-1)对种子的萌发有一定的促进作用,但不显著,6-BA浓度≥15 mg·L~(-1)则抑制种子的萌发。(4)用GA3500 mg·L~(-1)浸种后的种子发芽指标最好,发芽率、发芽势和发芽指数分别为69.67%、33.00%、4.51,种子的发芽起始时间和发芽持续时间分别为10.67 d、11.67 d。