阿尔茨海默症患者主要照顾者悲伤与照顾负担的相关性研究

[目的]探索阿尔茨海默症患者主要照顾者悲伤与照顾负担的相关性。[方法]采用Marwit-Meuser照顾者悲伤量表(MM-CGI)和照顾负担量表(CBI),选择2018年3月至2019年3月在开封市某三级甲等医院就诊的80名阿尔茨海默症患者,对其主要照顾者的悲伤和照顾负担情况进行调查。[结果]阿尔茨海默症照顾者悲伤总分为(56.46±7.92)分,照顾负担总分为(61.99±12.92)分,两者均处于中等偏高水平。阿尔茨海默症患者主要照顾者悲伤程度与照顾负担呈正相关。[结论]医护人员应探索积极、有效的干预措施应对阿尔茨海默症患者主要照顾者的悲伤情绪及其照顾负担。     

心理应激与多囊卵巢综合征中医发病机理的相关性

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性最常见的生殖内分泌疾病之一,心理应激因素是影响其发生、发展的重要原因之一。中医认为肾虚精亏是心理应激相关PCOS发病根本,而肝失疏泄是精神心理因素致病的重要环节,进而导致痰瘀互结,加重气血失调。目前已有许多研究证实现代医学的"心理应激"内涵与中医学"肝失疏泄"病机具有重要关联,但研究仍存在不足之处:"肾虚肝郁"在心理应激相关PCOS中发挥关键作用,但在基础实验研究方面,与其相关的动物模型仍局限于单纯的PCOS或心理障碍模型,尚缺乏与临床实际更贴合的复合模型;同时,结合心理应激研究PCOS的中医药相关防治报道较少,且研究中心局限,临床样本量不足。今后应从心理应激角度出发,通过基础实验建立更贴合临床实际的PCOS合并心理应激动物模型,为中医药干预心理应激相关PCOS提供研究基础;同时,将更多与心理障碍相关的临床指标应用于PCOS的临床试验中,从"方证对应"角度探讨中医药对PCOS的治疗效果,并进一步扩展研究中心,纳入更多样本进行系统分析;再次,临证治疗中应重视心理疏导在个体化治疗中的作用,以期取得更好的疗效。     

Measurement of landing mosquito density on humans

In traditional vector surveillance systems, adult mosquito density and the rate of mosquito-human host contact are estimated from the mosquito numbers captured in mechanical traps. But the design of the traps, their placement in the habitat and operating time, microclimate, and other environmental factors bias mosquito responses such that trapped mosquito numbers may be at variance with the numbers actually making human contact. As an alternative to mechanical traps, direct measurement of landing mosquito density enables real-time estimation of the mosquito–human-host-contact parameter. Based on this paradigm, we studied methods to measure mosquito landing responses to a human host. Our results showed: (a) an 18% difference (P < 0.0001) in the mean number of female Aedes albopictus (Skuse) making initial contact with the skin (9.11 ± 0.74 min^–1) compared with the number remaining on the skin for 5 s (7.42 ± 0.69 min^–1); (b) an increase (P < 0.05) in the mean per minute (min⁻¹) landing responses of Culex nigripalpus Theobald and Cx. quinquefasciatus Say with increased sampling time; (c) no difference (P > 0.55) in the average number of Ae. albopictus landing on the arm (8.6 ± 1.6 min^–1) compared with the leg (9.2 ± 2.5 min^–1) of the same human subject; (d) differences among day-to-day landing patterns for the mosquito species we studied but measurable periodicity (P < 0.05) in each case when daily patterns were averaged for four or more diel periods; and (e) an effect on landing mosquito density from air temperature (P < 0.0001) for Ae. albopictus and Cx. nigripalpus and dew point temperature (P < 0.0001) for Cx. quinquefasciatus. Results from this study were used to develop a procedure for safely and accurately measuring mosquito landing density on a human subject.     

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.All living cells are surrounded by a lipid membrane. Eukaryotic cells also contain several internal membrane-bound organelles, which enable them to compartmentalize related biological functions and thereby to enhance the efficiency of these processes. Phospholipids are the predominant component of these membranes. Their hydrophilic head groups interact with the cytosol, whereas their hydrophobic side chains are either buried within the hydrophobic interior of a typical membrane bilayer or interact with the hydrophobic neutral lipid core of lipoproteins and lipid droplets (LDs). Phospholipids are generally defined by their organic head group with phosphatidylcholine (PC) constituting over 50% of all membrane phospholipids. PC was first isolated in the 19th century and the major enzymatic pathway involved in its synthesis was revealed by Kennedy and Weiss (1) in the 1950s. Cells synthesize PC in three consecutive steps (Fig. 1A): choline kinase phosphorylates choline before choline phosphate cytidylyltransferase 1 α (encoded by the PCYT1A gene) generates the high-energy donor CDP-choline in the rate-limiting step of the pathway. In the last step, DAG:CDP-choline cholinephosphotransferase (CPT) uses CDP-choline and diacylglycerol (DAG) to form PC (2, 3).Open in a separate windowFig. 1.Cosegregation of biallelic PCYT1A mutations with fatty liver, low HDL cholesterol levels, lipodystrophy, insulin-resistant diabetes, and short stature. (A) Schematic illustration of the Kennedy PC synthesis pathway. CK, choline kinase; CPT, CDP-choline:1,2-diacylglycerol cholinephosphotransferase; PCYT1A, choline-phosphate cytidylyltransferase A, CTP:phosphocholine-cytidylyltransferase. (B) Family pedigrees of both probands demonstrating that only compound heterozygous carriers of PCYT1A mutations manifest fatty liver (red), low HDL cholesterol (blue), lipodystrophy (yellow), and insulin resistance/type 2 diabetes (T2DM) (green). PCYT1A mutation status, height (Ht.), and body mass index (BMI) are indicated below each individual’s symbol. ND, not determined; WT, wild type. (C) The location of PCYT1A mutations E280del, V142M, and 333fs in relation to known functional domains of PCYT1A. Domain M, membrane binding domain; domain P, phosphorylated region. (D) Conservation around the V142(red*) and E280(red*) mutation sites. Sequence alignment of representative metazoan sequences in the region surrounding the mutated residues. Hydrophobic (blue) and polar (green) residues interacting with V142 are highlighted. Only residues different from the human sequence are shown. Sequence IDs: human (Homo sapiens) {"type":"entrez-protein","attrs":{"text":"P49585","term_id":"166214967"}}P49585, zebrafish (Danio rerio) F1QEN6, sea squirt (Ciona intestinalis) {"type":"entrez-protein","attrs":{"text":"XP_002130773.1","term_id":"198437270"}}XP_002130773.1, sea urchin (Strongylocentrotus purpuratus) H3I3V9, water flee (Daphnia pulex) E9G1P5, Drosophila (D. melanogaster) Q9W0D9, Caenorhabditis (C. elegans) {"type":"entrez-protein","attrs":{"text":"P49583","term_id":"32172439"}}P49583, Trichoplax (T. adherens) B3RI62. (E and F) Structure of the catalytic domain of PCYT1A highlighting the role of V142M in the core packing. The two chains in the dimer are shown in yellow and gray; the residues and the secondary structure units are highlighted in color in the yellow monomer A: loop L3 with V142, red; α-helix, green; and the interacting β-sheet, blue. The residues packing with V142 are shown in ball-and-stick and space-filling representations, the dimer stabilizing R140 is shown in ball-and-stick colored according to the atom type. E is a global view, and F is a zoomed-in view of the catalytic core.Membrane phospholipids are a defining feature of advanced life-forms so it is perhaps not surprising that the pathways involved in their synthesis are ancient, and mutations affecting them are rarely tolerated in evolution. Here, we describe the identification and characterization of pathogenic human loss-of-function mutations affecting the eponymous Kennedy pathway.     

Pharmacological inhibition of TLR4/NF‐κB with TLR4‐IN‐C34 attenuated microcystin‐leucine arginine toxicity in bovine Sertoli cells

This study investigated the pharmacological inhibition of the toll‐like receptor 4 (TLR4) genes as a measure to attenuate microcystin‐LR (MC‐LR) reproductive toxicity. Bovine Sertoli cells were pretreated with TLR4‐IN‐C34 (C34) for 1 hour. Thereafter the pretreated and non‐pretreated Sertoli cells were cultured in medium containing 10% heat‐activated fetal bovine serum + 80 μg/L MC‐LR for 24 hours to assess the ability of TLR4‐IN‐C34 to attenuate the toxic effects of MC‐LR. The results showed that TLR4‐IN‐C34 inhibited MC‐LR‐induced mitochondria membrane damage, mitophagy and downregulation of blood‐testis barrier constituent proteins via TLR4/nuclear factor‐kappaB and mitochondria‐mediated apoptosis signaling pathway blockage. The downregulation of the mitochondria electron transport chain, energy production and DNA replication related genes (mt‐ND2, COX‐1, COX‐2, ACAT, mtTFA) and upregulation of inflammatory cytokines (interleukin [IL]‐6, tumor necrosis factor‐α, IL‐1β, interferon‐γ, IL‐4, IL‐10, IL‐13 and transforming growth factor β1) were modulated by TLR4‐IN‐C34. Taken together, we conclude that TLR4‐IN‐C34 inhibits MC‐LR‐related disruption of mitochondria membrane, mitophagy and downregulation of blood‐testis barrier proteins of the bovine Sertoli cell via cytochrome c release and TLR4 signaling blockage.     

Phloroglucinol averts isoprenaline hydrochloride induced myocardial infarction in rats

Myocardial infarction (MI) is indicated by the symptoms like sharp chest pain, sweating, palpitations, and nervousness finally leading to heart attack. MI occurs mainly due to the risk factors like smoking, elevated blood pressure, diabetes, hypercholesterolemia, obesity, decreased HDL level, elevated LDL level, hyperlipoproteinemia and aging consequently leads to demandable coronary blood supply, oxidative stress, and acute necrosis of the myocardium. Cardioprotective potential of the phloroglucinol (PG) was assessed by treating isoprenaline hydrochloride (ISO; 85 mg/kg b.w., s.c.) induced MI model in rats. Pretreatment with PG in a dose of 30 mg/kg was done for 28 days and followed by ISO (for MI induction) on 29th and 30th days, exhibited decline in the abnormalities in the ECG patterns, cardiac marker enzymes, enzymic and nonenzymic antioxidants, lipid peroxidation, lipid profiles, and histopathological investigations compared to isoprenaline alone treated group. On the whole, the present investigations elucidate the significance of PG in alleviating the pathological process and appreciably prevent the induction of MI in experimental rats.     

外周血宏基因组二代测序对肺孢子菌肺炎的诊断价值

目的:研究探讨外周血宏基因组二代测序技术(mNGS)在免疫抑制剂治疗的肾脏疾病患者合并肺孢子菌肺炎(PCP)的诊断价值。方法:选取肾脏疾病接受免疫抑制治疗后合并弥漫性肺部感染、临床拟诊为PCP的患者37例作为观察组,另选取25例临床确诊为其他病原导致肺部感染的患者作为对照。使用mNGS检测患者外周血中的病原种类和序列,评价mNGS对PCP的检测效能,比较mNGS与传统临床诊断PCP方法(真菌G联合乳酸脱氢酶检测)的效能差异。结果:观察组患者送检外周血样本37份,其中35份mNGS检出耶氏肺孢子菌(PJ)序列,敏感度94.59%,特异度100%;31例患者为混合型感染,27例检出病毒序列(19例为巨细胞病毒),8例合并细菌感染。对照组25份血标本PJ序列均为阴性。真菌G联合乳酸脱氢酶检测的敏感度89.19%,特异度56.0%;mNGS的特异度显著高于真菌G联合乳酸脱氢酶检测。结论:mNGS较传统诊断PCP的方法有明显优势,可同时检出混合感染的病原,对免疫抑制合并肺部感染的诊断有重要意义。