BACKGROUND & AIMS: :The effects of exercise on hypocholesterolemia, one of the risk factors of cerebrovascular disorders, were examined. 47-51-day-old stroke-prone spontaneously hypertensive rats (stroke-prone SHRs) were assigned to 2 groups, sedentary or exercise, and raised for 8 weeks. The total serum cholesterol level of the exercised group was 17-18% higher (P less than 0.01) than the control group, and the level of cholesterol synthesis in the liver of the former group significantly higher than in the latter. On the other hand, the level of intestinal cholesterol synthesis in the exercised group was significantly lower. The activity of HMG-CoA reductase in the liver microsomes was significantly increased by exercise, but the activity of this enzyme in the small intestine was not affected. A significant correlation was observed between the rate of cholesterol synthesis in the liver and the amount of radiolabeled cholesterol released into the serum. From these results, we conclude that the enhancement of the synthesis and the release of cholesterol in the liver by exercise is a major cause of the exercise-induced increase in serum cholesterol of stroke-prone SHRs.

背景与目标： ：检查了运动对低胆固醇血症的影响，低胆固醇血症是脑血管疾病的危险因素之一。将47-51天大的易发中风自发性高血压大鼠（易发中风SHR）分为两组，久坐或运动，并饲养8周。运动组的总血清胆固醇水平比对照组高17-18％（P小于0.01），前者肝脏的胆固醇合成水平明显高于后者。另一方面，运动组的肠道胆固醇合成水平明显降低。运动后，肝微粒体中HMG-CoA还原酶的活性显着增加，但该酶在小肠中的活性并未受到影响。观察到肝脏中胆固醇的合成速率与释放到血清中的放射性标记胆固醇的量之间存在显着相关性。根据这些结果，我们得出结论，通过运动增强肝脏中胆固醇的合成和释放是运动引起的中风倾向性SHRs血清胆固醇升高的主要原因。

BACKGROUND & AIMS: :Plasma cholesterol concentrations were determined in 83 acute myeloid leukemia patients. Mean plasma cholesterol concentration (+/- S.D.) at the time of diagnosis was 2.91 mmol/L (+/- 1.13). The percentage of AML patients having hypocholesterolemia was 90.4 per cent. The lowest cholesterol levels were observed in the poorly differentiated FAB subtypes of acute myeloid leukaemia: AMyL(M1) and AMoL(M5a). The results showed that the initial hypocholesterolemia in acute myeloid leukemia is significantly related to the degree of both cytological and cytochemical maturation of leukemic blast cells at diagnosis. The degree of maturation at diagnosis has been shown to be related to prognosis in favour of more differentiated subtypes of acute myeloid leukemia. Also, hypocholesterolemia has been shown in several epidemiological studies to be related to an increased mortality from human cancer. Therefore, the degree of maturation may serve as a link between hypocholesterolemia and the increased mortality from human cancer.

背景与目标： ：在83例急性髓性白血病患者中测定血浆胆固醇浓度。诊断时的平均血浆胆固醇浓度（/-S.D.）为2.91 mmol / L（/-1.13）。低胆固醇血症的AML患者的百分比为90.4％。在急性髓性白血病的低分化FAB亚型中观察到最低的胆固醇水平：AMyL（M1）和AMoL（M5​​a）。结果表明，急性髓细胞性白血病的初始低胆固醇血症与诊断时白血病母细胞的细胞学和细胞化学成熟程度密切相关。已证实诊断时的成熟程度与预后有关，有利于急性髓性白血病的更多分化亚型。此外，低胆固醇血症在一些流行病学研究中已显示出与人类癌症的死亡率增加有关。因此，成熟度可以作为低胆固醇血症与人类癌症死亡率增加之间的联系。

BACKGROUND & AIMS: The evidence relating hypocholesterolemia to an increased risk of cancer is controversial. Although more than a dozen populations have been studied in prospective epidemiological investigations, there is relatively little consistency relating low serum cholesterol levels to future risk or mortality from cancer. Several studies have demonstrated a significant inverse relationship, but many others have failed to do so, and there is no ready explanation for the divergence of results. The data from dietary studies, both at the group level and at the individual level, indicate that, if anything, higher intakes of cholesterol appear to be related to cancer rather than lower levels. A potential role for vitamin A and for some genetic predisposition to cancer perhaps associated with lower cholesterol absorption and decreased degradation of cholesterol in the gut may possibly explain some of these inconsistencies. It is concluded that(a) the available data do not substantiate any direct cause and effect relationship between low blood cholesterol levels and cancer. Rather, the data suggest that low cholesterol levels may serve as a "marker," possibly genetic, and in only small numbers of male individuals in any given population; (b) the data do not preclude, countermand, or contradict the current public health message which recommends that those with elevated cholesterol levels seek to lower them through diets lower in saturated fat and cholesterol.

背景与目标： 将低胆固醇血症与增加的癌症风险相关的证据是有争议的。尽管在前瞻性流行病学研究中已经研究了十几个人群，但将血清胆固醇水平低与未来癌症风险或死亡率相关的一致性相对较低。几项研究已证明存在显着的反比关系，但许多其他研究却未能做到，而且还没有现成的解释结果差异的现成解释。来自饮食研究的数据，无论是在小组水平还是在个体水平，都表明，胆固醇摄入量的增加（如果有的话）似乎与癌症有关，而不是胆固醇水平的降低。维生素A和某些遗传易感性癌症的潜在作用（可能与胆固醇吸收降低和肠内胆固醇降解降低有关）可能解释了其中的一些矛盾之处。结论是：（a）现有数据不能证实低胆固醇水平与癌症之间的任何直接因果关系。相反，数据表明低胆固醇水平可能是“标记”，可能是遗传的，并且在任何给定人群中只有少数男性个体。 （b）数据不排除，抵制或与当前的公共卫生信息相抵触，该信息建议胆固醇水平高的人通过降低饱和脂肪和胆固醇的饮食来降低胆固醇。

BACKGROUND & AIMS: OBJECTIVES:The aim of this study is to identify variables at diagnosis to predict the subsequent relapse in patients with Takayasu arteritis (TA). METHODS:We retrospectively analyzed 33 patients with TA in our hospitals from April 2000 to July 2015. We collected baseline variables at diagnosis including clinical symptoms and laboratory data using medical records and investigated associations of these indices with subsequent relapses. RESULTS:The patients included two males and 31 females (94%). The median age at diagnosis was 39 years old, and the median follow-up duration was 90 months. Relapse was noted in 18 patients (55%). Only lower total cholesterol (Tcho) [median, 117 mg/dL (relapse) vs. 182 mg/dL (nonrelapse)] was preferentially distributed in the relapse group as compared with the non-relapse group. Multivariable logistic analysis showed that hypocholesterolemia (<150 mg/dL) at diagnosis was the only predictor of subsequent relapse (odds ratio: 5.43, 95% confidence interval: 1.13-30.19; p = 0.035). The nonrelapse survival rate was significantly lower in the group with a Tcho level <150 mg/dL by Kaplan-Meier estimate (p < 0.001). CONCLUSIONS:We found that hypocholesterolemia at diagnosis is a predictor of subsequent relapse in patients with TA.

背景与目标： 目的：本研究的目的是确定诊断中的变量，以预测高枝动脉炎（TA）患者随后的复发。
方法：我们回顾性分析了2000年4月至2015年7月在我院接受治疗的33例TA患者。我们收集了诊断时的基线变量，包括临床病历和医疗记录，并根据病历对这些指标与随后复发的关系进行了调查。
结果：患者包括2例男性和31例女性（94％）。诊断时的中位年龄为39岁，中位随访时间为90个月。 18例（55％）患者出现复发。与非复发组相比，复发组仅优先分配较低的总胆固醇（Tcho）[中位数，117 mg / dL（复发）对182 mg / dL（非复发）]。多变量逻辑分析表明，诊断时的低胆固醇血症（<150 mg / dL）是随后复发的唯一预测因素（几率：5.43，95％置信区间：1.13-30.19； p = 0.035）。根据Kaplan-Meier估计，Tcho水平<150 mg / dL的组中非复发存活率显着降低（p <0.001）。
结论：我们发现诊断时的低胆固醇血症是TA患者随后复发的预测指标。

BACKGROUND & AIMS: PURPOSE:Persons with total cholesterol (TC) levels less than 130 mg/dL (less than 3.26 mmol/L) make up less than 1% of a healthy population. Causes of hypocholesterolemia include a diet very low in cholesterol and saturated fat, disease, genetic factors (including low apolipoprotein B-100 [apo B-100] and the apo E allele), and drug therapy. The purpose of this study was to determine the causes of hypocholesterolemia in a healthy Kaiser Foundation Health Plan (KFHP) population. PATIENTS AND METHODS:We conducted a dietary and health survey of 201 healthy hypocholesterolemic adults (range: 2.04 to 3.88 mmol/L [79 to 150 mg/dL]) and 200 matched control subjects with TC levels in the middle quintile of the population (range: 5.0 to 5.61 mmol/L [194 to 217 mg/dL]) who had routine health screening from 1983 through 1985. We did apo E phenotyping studies and lipid and apo A-1 and B-100 measurements in a subgroup of 45 hypocholesterolemic subjects (mean TC level: 3.26 mmol/L [126 mg/dL]) and in a comparison group of 49 unmatched volunteers (mean TC level: 5.04 +/- 0.75 mmol/L [195 +/- 29 mg/dL]). RESULTS:We found no differences in dietary intake or clinically significant medical illness between hypocholesterolemic and control subjects. In the hypocholesterolemic subgroup, we found an increased frequency of the apo E2 allele (epsilon 2) and a decreased frequency of the apo E4 allele (epsilon 4); the frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles were 33.3%, 63.3%, and 3.3%, respectively. The corresponding apo E allele frequencies in the comparison subgroup were 8.2%, 73.5%, and 18.4%, similar to those previously reported for the general population and significantly different from those found in the hypocholesterolemic subgroup (p < 0.0001). One hypocholesterolemic subject (a 46th patient) had a mutation in the apo B gene that resulted in the synthesis of a truncated species of apo B (apo B-46). CONCLUSION:Our study indicates that hypocholesterolemia in our KFHP urban population is usually not caused by diet or disease. Biochemical factors, including the increased frequency of the apo E-2 phenotype and the decreased frequency of the apo E-4 phenotype, are more important.

背景与目标： 目的：总胆固醇（TC）水平低于130 mg / dL（低于3.26 mmol / L）的人占健康人口的比例不到1％。低胆固醇血症的原因包括低胆固醇和饱和脂肪的饮食，疾病，遗传因素（包括低载脂蛋白B-100 [apo B-100]和apo E等位基因）以及药物治疗。这项研究的目的是确定健康的Kaiser基金会健康计划（KFHP）人群低胆固醇血症的原因。
患者和方法：我们对201名健康的低胆固醇血症成年人（范围：2.04至3.88 mmol / L [79至150 mg / dL]）和200名匹配的对照组受试者进行了饮食和健康调查，这些受试者的TC含量处于中五分位数（范围：5.0至5.61 mmol / L [194至217 mg / dL]），他们从1983年到1985年进行了常规健康检查。我们在45个亚组中进行了载脂蛋白E表型研究以及脂质和载脂蛋白A-1和B-100的测量。低胆固醇血症受试者（平均TC水平：3.26 mmol / L [126 mg / dL]）和49名不匹配志愿者的比较组（平均TC水平：5.04 /-0.75 mmol / L [195 /-29 mg / dL]）。
结果：我们发现低胆固醇血症的人与对照组之间在饮食摄入或临床重大医学疾病方面没有差异。在低胆固醇血症亚组中，我们发现apo E2等位基因（ε2）的频率增加，而apo E4等位基因（ε4）的频率降低； ε2，ε3和ε4等位基因的频率分别为33.3％，63.3％和3.3％。比较亚组中相应的apo E等位基因频率为8.2％，73.5％和18.4％，与先前报道的一般人群的频率相似，并且与低胆固醇血症亚组中的频率显着不同（p <0.0001）。一名低胆固醇血症的受试者（第46名患者）的apo B基因突变，导致apo B的截短种（apo B-46）的合成。
结论：我们的研究表明，KFHP城市人口的低胆固醇血症通常不是由饮食或疾病引起的。更重要的是生化因素，包括载脂蛋白E-2表型频率的增加和载脂蛋白E-4表型频率的降低。

BACKGROUND & AIMS: :The oxidative stress levels in plasma and hemolysate and cholesterol levels in plasma of sickle cell anemia patients, carriers and controls were evaluated. A total of 40 cases-17 patients, 13 carriers and 10 controls-were involved in the study. Plasma and hemolysate malondialdehyde (MDA) were detected via thiobarbituric acid reaction with a fluorimetric detector by high-performance liquid chromatography system. Plasma cholesterol was determined by enzymatic colorimetric method. Mean MDA levels of SCA patients were higher than those of the carriers' and healthy children's both in plasma and in hemolysate (P < 0.005). The mean plasma and hemolysate MDA levels were 25.3 ± 1.6 nmol/l and 86.7 ± 19.3 nmol/l in patients, 19.1 ± 0.8 nmol/l and 54.1 ± 10.8 nmol/l in carriers and 19.6 ± 0.8 nmol/l and 56.8 ± 9.3 nmol/l in healthy children. Mean plasma total cholesterol levels were 92.1 ± 19.1 mg/dl in patients, 116.2 ± 23.3 mg/dl in carriers and 126.6 ± 16.4 mg/dl in controls (P < 0.005). There was a significant negative correlation of -0.520 between hemolysate MDA and plasma cholesterol levels in patients (P < 0.05). The degree of correlation increased up to -0.782 (P = 0.008) in the patients with HbSS phenotype. This negative correlation between MDA and cholesterol may imply a potential association between oxidative stress and hypocholesterolemia in sickle cell anemia.

背景与目标： ：评估镰状细胞性贫血患者，携带者和对照者血浆中的氧化应激水平和溶血产物以及血浆中的胆固醇水平。该研究共涉及40例17例患者，13例携带者和10例对照。血浆和溶血产物丙二醛（MDA）通过高效液相色谱系统与荧光检测器通过硫代巴比妥酸反应进行检测。血浆胆固醇通过酶比色法测定。血浆和溶血产物中SCA患者的平均MDA水平均高于携带者和健康儿童的MDA水平（P <0.005）。患者的平均血浆和溶血产物MDA水平为25.3±1.6 nmol / l和86.7±19.3 nmol / l，携带者为19.1±0.8 nmol / l和54.1±10.8 nmol / l，携带者为19.6±0.8 nmol / l和56.8±9.3健康儿童的nmol / l。患者的平均血浆总胆固醇水平为92.1±19.1 mg / dl，携带者为116.2±23.3 mg / dl，对照为126.6±16.4 mg / dl（P <0.005）。患者的溶血产物MDA与血浆胆固醇水平呈显着负相关-0.520（P <0.05）。 HbSS表型患者的相关程度增加至-0.782（P = 0.008）。 MDA与胆固醇之间的这种负相关性可能暗示镰状细胞性贫血中氧化应激与低胆固醇血症之间可能存在关联。

BACKGROUND & AIMS: :A case of pyridoxine-responsive anemia with hypolipidemia and hypocholesterolemia responsive to pyridoxine is presented. It is suggested that abnormalities of the serum lipids are common but often unrecognized in patients with pyridoxine-responsive anemia. A mechanism to explain their occurrence is postulated.

背景与目标： ：介绍一例吡ido醇反应性贫血，对吡ido醇反应低脂血症和低胆固醇血症。提示在吡ido醇反应性贫血患者中血脂异常是常见的，但常常未被发现。提出了一种解释其发生的机制。

BACKGROUND & AIMS: OBJECTIVE:The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene encodes a proprotein convertase that causes degradation of cell surface low-density lipoprotein receptors (LDLRs). Mutations in the PCSK9 gene that disrupt the normal function of PCSK9 could therefore result in increased number of LDLRs and hypocholesterolemia. Also, the cholesterol-lowering effect of statins could be increased in subjects carrying mutations in the PCSK9 gene. METHODS AND RESULTS:We have screened 38 unrelated hypocholesterolemic subjects as well as 25 unrelated familial hypercholesterolemia (FH) heterozygotes who responded particularly well to statin therapy for mutations in the 12 exons of the PCSK9 gene by DNA sequencing. Six of the 38 (15.8%) hypocholesterolemic subjects were heterozygous for 1 of the 3 mutations R46L, G106R, or R237W in the PCSK9 gene. In the group of 25 FH heterozygotes who responded particularly well to statin therapy, 3 (8.8%) were heterozygous for mutations R46L or N157K in the PCSK9 gene. None of 441 hypercholesterolemic subjects without mutations in the LDLR gene or in the apolipoprotein B-100 gene possessed any of the 4 mutations. CONCLUSIONS:The 4 missense mutations R46L, G106R, N157K, and R237W are associated with hypocholesterolemia and possibly increased response to statin therapy.

背景与目标： 目的：前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）基因编码的前蛋白转化酶会导致细胞表面低密度脂蛋白受体（LDLRs）降解。因此，破坏PCSK9正常功能的PCSK9基因突变可能导致LDLR数量增加和低胆固醇血症。此外，在携带PCSK9基因突变的受试者中，他汀类药物的降胆固醇作用可能会增强。
方法和结果：我们筛选了38名无关的低胆固醇血症受试者以及25名无关的家族性高胆固醇血症（FH）杂合子，他们对他汀类药物疗法的PCSK9基因12个外显子突变反应特别好。 38名低胆固醇血症受试者中的6名（15.8％）对PCSK9基因的3个突变R46L，G106R或R237W中的1个是杂合的。在对他汀类药物治疗反应特别好的25个FH杂合子中，有3个（8.8％）对PCSK9基因中的R46L或N157K突变是杂合的。在LDLR基因或载脂蛋白B-100基因中没有突变的441名高胆固醇血症受试者中，没有一个具有这四个突变。
结论：4个错义突变R46L，G106R，N157K和R237W与低胆固醇血症有关，并可能增加对他汀类药物治疗的反应。

BACKGROUND & AIMS: :Mature healthy female Japanese quails injected (i.p.) with gemfibrozil at two dose levels for 1,2,3 and 4 weeks induced hypocholesterolemia as observed by the serum cholesterol concentration which was more severe with the higher dose. Liver and ovarian cholesterol contents decreased in 3rd and 4th week of the treatment. Significant (P > 0.05) increase in serum triiodothyronine (T3) and thyroxine (T4) level were observed between 3rd and 4th week while serum estradiol-17 beta and progesterone levels declined continuously from Ist week till the termination of the treatment. The quantity and quality of the eggs produced by the treated quails were inferior. These results indicate that induction of hypocholesterolemia impaired the reproductive efficiency of quails.

背景与目标： ：以1,2,3和4周两种剂量注射吉非贝齐（i.p.）的成熟健康的女性日本鹌鹑，分别在1,2,3和4周内诱发了低胆固醇血症，这是通过血清胆固醇浓度观察到的，随着剂量的增加胆固醇胆固醇浓度会升高。在治疗的第3周和第4周，肝和卵巢胆固醇含量降低。从第3周到​​第4周，血清三碘甲状腺素（T3）和甲状腺素（T4）水平显着（P> 0.05）升高，而血清雌二醇-17β和孕酮水平从治疗第1周开始持续下降。经处理的鹌鹑生产的鸡蛋的数量和质量较差。这些结果表明低胆固醇血症的诱导损害了鹌鹑的繁殖效率。

BACKGROUND & AIMS: :Tumor-suppressor Pdcd4 inhibits transformation and invasion and is downregulated in cancers. So far, it has not been studied as to whether miRNAs, suppressing target expression by binding to the 3'-UTR, regulate Pdcd4 or invasion. The present study was conducted to investigate the regulation of Pdcd4, and invasion/intra-vasation, by miRNAs. A bioinformatics search revealed a conserved target-site for miR-21 within the Pdcd4-3'-UTR at 228-249 nt. In 10 colorectal cell lines, an inverse correlation of miR-21 and Pdcd4-protein was observed. Transfection of Colo206f-cells with miR-21 significantly suppressed a luciferase-reporter containing the Pdcd4-3'-UTR, whereas transfection of RKO with anti-miR-21 increased activity of this construct. This was abolished when a construct mutated at the miR-21/nt228-249 target site was used instead. Anti-miR-21-transfected RKO cells showed an increase of Pdcd4-protein and reduced invasion. Moreover, these cells showed reduced intra-vasation and lung metastasis in a chicken-embryo-metastasis assay. In contrast, overexpression of miR-21 in Colo206f significantly reduced Pdcd4-protein amounts and increased invasion, while Pdcd4-mRNA was unaltered. Resected normal/tumor tissues of 22 colorectal cancer patients demonstrated an inverse correlation between miR-21 and Pdcd4-protein. This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation/metastasis.

背景与目标： ：肿瘤抑制因子Pdcd4抑制转化和侵袭，并在癌症中下调。到目前为止，尚未研究miRNA是否通过与3'-UTR结合来抑制靶标表达，调节Pdcd4或入侵。进行本研究以研究miRNA对Pdcd4的调控以及侵袭/血管内侵袭。生物信息学搜索显示，Pdcd4-3'-UTR中miR-21的保守靶位点为228-249 nt。在10个结直肠细胞系中，观察到miR-21与Pdcd4-蛋白呈负相关。用miR-21转染Colo206f细胞可显着抑制含有Pdcd4-3'-UTR的荧光素酶报告基因，而用抗miR-21转染RKO可提高该构建体的活性。当使用在miR-21 / nt228-249靶位点突变的构建体代替时，这种情况就被取消了。抗miR-21转染的RKO细胞显示Pdcd4蛋白增加，侵袭减少。此外，在鸡胚转移试验中，这些细胞显示出减少的血管内转移和肺转移。相反，在Colo206f中miR-21的过表达显着减少了Pdcd4蛋白的含量并增加了侵袭，而Pdcd4-mRNA却没有改变。切除的22例结直肠癌患者的正常/肿瘤组织显示miR-21与Pdcd4-蛋白呈负相关。这是第一项显示Pdcd4受miR-21负调控的研究。此外，这是第一个证明miR-21诱导侵袭/浸润/转移的报告。

BACKGROUND & AIMS: :High-density lipoprotein (HDL) mediated reverse cholesterol transport (RCT) is regarded to be crucial for prevention of foam cell formation and atherosclerosis. ABC-transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) are involved in the biogenesis of HDL and the selective delivery of HDL cholesterol to the liver, respectively. In the present study, we phenotypically characterized mice lacking these two proteins essential for HDL metabolism. ABCA1×SR-BI double knockout (dKO) mice showed severe hypocholesterolemia mainly due to HDL loss, despite a 90% reduction of HDL cholesterol uptake by liver. VLDL production was increased in dKO mice. However, non-HDL cholesterol levels were reduced, probably due to enhanced clearance via LRP1. Hepatobiliary cholesterol transport and fecal sterol excretion were not impaired in dKO mice. In contrast, the macrophage RCT in dKO mice was markedly impaired as compared to WT mice, associated with the accumulation of macrophage foam cells in the lung and Peyer's patches. Strikingly, no atherosclerotic lesion formation was observed in dKO mice. In conclusion, both ABCA1 and SR-BI are essential for maintaining a properly functioning HDL-mediated macrophage RCT, while the potential anti-atherosclerotic functions of ABCA1 and SR-BI are not evident in dKO mice due to the absence of pro-atherogenic lipoproteins.

背景与目标： ：高密度脂蛋白（HDL）介导的胆固醇逆向转运（RCT）被认为对于预防泡沫细胞形成和动脉粥样硬化至关重要。 ABC转运蛋白A1（ABCA1）和清道夫受体BI（SR-BI）分别参与HDL的生物发生和HDL胆固醇向肝脏的选择性递送。在本研究中，我们在表型上表征了缺少这两种对HDL代谢必不可少的蛋白质的小鼠。尽管肝脏对HDL胆固醇的吸收降低了90％，但ABCA1xSR-BI双敲除（dKO）小鼠仍表现出严重的低胆固醇血症，这主要是由于HDL丢失所致。在dKO小鼠中VLDL产生增加。但是，非HDL胆固醇水平降低了，这可能是由于通过LRP1的清除率提高了。 dKO小鼠的肝胆胆固醇转运和粪便固醇排泄没有受到损害。相比之下，与WT小鼠相比，dKO小鼠的巨噬细胞RCT明显受损，这与肺和Peyer斑块中巨噬细胞泡沫细胞的积累有关。令人惊讶的是，在dKO小鼠中未观察到动脉粥样硬化病变的形成。总之，ABCA1和SR-BI对于维持正常运转的HDL介导的巨噬细胞RCT都是必不可少的，而dKO小鼠中ABCA1和SR-BI的潜在抗动脉粥样硬化功能由于缺乏促动脉粥样硬化的脂蛋白而并不明显。

BACKGROUND & AIMS: BACKGROUND:In vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterol's immunomodulatory properties, may interact. METHODS:Fasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; <150 mg/dl) or non-HypoCHL (>150 mg/dl) and were compared on viro-immune outcomes. RESULTS:At baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 +/- 181 vs. 295 +/- 191 cells/mm3, p = 0.02) and CD8 (823 +/- 448 vs. 1194 +/- 598 cells/mm3, p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non-HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1-2.6, p = 0.05) and to exhibit <200 CD4 (95% CI 1.03-2.9, p = 0.04) compared with non-HypoCHL. Low thymic output was related to poorer CD4 cell response in HypoCHL subjects. Analyses suggest a dose-response relationship with every increase of 50 mg/dl in cholesterol related to a parallel rise of 50 CD4 cells. CONCLUSIONS:The study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance.

背景与目标： 背景：体外研究表明，降低胆固醇可抑制HIV复制。但是，这种作用可能在体内不起作用，在这种情况下，其他因素（例如胆固醇的免疫调节特性）可能会相互作用。
方法：在基线时以及在高活性抗逆转录病毒疗法（HAART）24周后，从165名HIV感染者中获取了快速的血液样本。参加者分为低胆固醇血症（HypoCHL; <150 mg / dl）或非HypoCHL（> 150 mg / dl），并进行病毒免疫结果比较。
结果：在基线时，HypoCHL（40％）的参与者表现出较低的CD4（197 /-181 vs.295 /-191细胞/ mm3，p = 0.02）和CD8（823 /-448与1194 /-598细胞/ mm3 ，p = 0.001）计数，并且比非HypoCHL对照更有可能检测到病毒载量（OR = 3.5，p = 0.01）。在进行HAART后，HypoCHL参与者的病毒学失败> 400份（95％CI 1-2.6，p = 0.05）和表现出<200 CD4（95％CI 1.03-2.9，p = 0.04）的可能性是其两倍。非HypoCHL。低胸腺输出与HypoCHL受试者较差的CD4细胞反应有关。分析表明，每增加50 mg / dl胆固醇就会引起剂量-反应关系，这与50个CD4细胞的平行增加有关。
结论：该研究首次涉及HypoCHL与HAART有效性受损，包括胸腺对CD4的补充有限以及病毒清除不足。

BACKGROUND & AIMS: :Hypocholesterolemia is a well-documented phenomenon associated with a variety of hematological malignancies and nonmalignant disorders associated with splenomegaly. To determine the incidence of hypocholesterolemia in patients with hairy cell leukemia (HCL), we measured the serum cholesterol levels before and after a single cycle of 2-chlorodeoxyadenosine (2-CdA) in 46 patients. The mean pre-treatment serum cholesterol level was 152.8 mg/dl (range, 60 to 293 mg/dl). The mean post-treatment serum cholesterol level was 190.0 mg/dl. This was significantly higher than the pre-treatment values (P <0.0001). Twelve patients who had previously undergone splenectomy showed a similar response to treatment, with a pre-treatment value of 180.0 mg/dl and a post-treatment value of 219.8 mg/dl (P < 0.0001). However, there was a significant difference in the pre-treatment serum cholesterol levels in the nonsplenectomized patients (143.0 mg/dl) compared to the splenectomized patients (180.0 mg/dl) (P < 0.03). The pre-treatment serum cholesterol did not correlate with the pre-treatment splenic index (correlation coefficient = -0.39, P < 0.065). Similarly, there was no correlation between the change in splenic index and the change in serum cholesterol level post-treatment. These findings suggest that hypocholesterolemia in HCL is related to tumor burden and not to splenomegaly alone. Since cholesterol is critical to hairy cell metabolism and structure, treatment strategies interfering with cholesterol synthesis may be productive.

背景与目标： 低胆固醇血症是一种有据可查的现象，与多种血液恶性肿瘤和与脾肿大相关的非恶性疾病有关。为了确定毛细胞白血病（HCL）患者低胆固醇血症的发生率，我们测量了46位患者单周期2-氯脱氧腺苷（2-CdA）前后的血清胆固醇水平。治疗前的平均血清胆固醇水平为152.8 mg / dl（范围为60至293 mg / dl）。治疗后平均血清胆固醇水平为190.0 mg / dl。这显着高于治疗前的值（P <0.0001）。十二名先前接受脾切除术的患者对治疗表现出相似的反应，治疗前值为180.0 mg / dl，治疗后值为219.8 mg / dl（P <0.0001）。但是，未脾切除的患者（143.0 mg / dl）与经脾切除的患者（180.0 mg / dl）相比，治疗前血清胆固醇水平存在显着差异（P <0.03）。治疗前血清胆固醇与治疗前脾脏指数无关（相关系数= -0.39，P <0.065）。同样，治疗后脾指数的变化与血清胆固醇水平的变化之间也没有相关性。这些发现表明，HCL中的低胆固醇血症与肿瘤负荷有关，而与单独的脾肿大无关。由于胆固醇对于毛细胞的代谢和结构至关重要，因此干扰胆固醇合成的治疗策略可能会产生效果。