血清RBP、CysC测定在肝、肾疾病诊断中的应用

目的建立免疫比浊法测定血清视黄醇结合蛋白（RBP）和胱抑素C（Cys C）的方法,探讨血清RBP、Cys C联合在肝肾疾病诊断中价值。方法用免疫比浊法测定肝病患者76人、肾病患者54人和正常人37人血清中RBP和Cys C的含量,根据NCCLS相关文件对其进行精密度、线性、准确度等方法学评价以及临床应用初探。结果 （1）健康对照组血清RBP含量为（49.7±13.2）mg/L,肾病组血清RBP含量为（88.8±34.1）mg/L,肾病组与对照组比较P〈0.01,差异有统计学意义;肝病组血清RBP含量为（19.7±11.4）mg/L,肝病组与对照组比较P〈0.01,差异有统计学意义。（2）健康对照组血清Cys C含量为（0.92±0.61）mg/L,肾病组血清Cys C含量为（3.3±2.0）mg/L,肾病组与对照组比较P〈0.01,差异有统计学意义;肝病组总的血清Cys C含量为（0.92±0.25）mg/L,肝病组与对照组比较P〉0.05,差异无统计学意义。结论两种测定物对肾疾病的诊断都有临床意义,两种物质联合诊断可提高诊断率,RBP在肝脏疾病中有诊断意义,而Cys C对肝脏疾病无诊断意义。     

RBP对肾脏早期损害的诊断价值

目的:探讨视黄醇结合蛋白(RBP)检测对肾脏功能早期损害的应用价值。方法:我院糖尿病科及高血压病专科住院及门诊病人标本(糖尿病均为2型糖尿病),共926份,包括血液、尿液(晨尿),对所有血液标本进行RBP、胱抑素C(CysC)、β2-微球蛋白(β2-M)、尿素氮(BUN)、肌酐(Cr)的检测;对RBP结果在70～120mg/L之间的患者进行尿液的RBP、β2-M、尿微量白蛋白(U-Alb)、Cr的检测,并进行统计学分析。结果:RBP测定结果正常时,CysC、β2-M、Cr、BUN都在正常范围之内,当RBP出现轻度升高时,CysC、β2-M同步升高,并与对照组有显著差异,而BUN、Cr均无明显变化,但随着前种指标的明显升高,BUN、Cr也有着相应的改变,但其程度不显著。尿液标本中,变化最显著的依次为RBP、β2-M、CysC、Alb,而Cr几乎无变化。结论:在糖尿病、高血压等疾病的早期,引起肾小球滤过率或肾血流量降低时,致使血液中RBP蓄积而使之浓度升高,其敏感性远高于Cr、BUN,与CysC、β2-M相当。在出现明显肾脏损害时,其升高的程度也与CysC相当,高于β2-M(两组比较P<0.05),当造成早期近端肾小管损伤时,RBP、CysC、β2-M在尿液中的浓度升高十分明显,而尿液中的肌酐几乎无变化,且RBP升高程度大于β2-M、CysC、Alb等(P<0.05)。     

CysC和NRBP联合测定在肿瘤化疗患者早期肾损伤监测中的应用

目的探讨血清半胱氨酸蛋白酶抑制剂C（CystainC,CysC）和视黄醇结合蛋白（Retinol-Binding,RBP）联合测定在肿瘤化疗患者早期肾损伤监测中的应用。方法对照组60例,为健康体检无肾脏病史,且尿蛋白定性为阴性者;试验组为27例肿瘤化疗患者,检测BUN、Crea、CysC、RBP四个指标,并进行统计学分析。结果BUN浓度对照组为（3．4±1．12）mmol／L,试验组为（4．44±1．38）mmol／L;Crea浓度对照组为（69．04±220．77）μmol/L,试验组为（80．33±26．23）μmol／L;CysC浓度对照组为（0．85±0．13）mg／L,试验组为（1．70±0．49）mg／L;RBP浓度对照组为（48．21±14.3）mg／L,试验组为（82．59±14．08）mg／L。结论联合检测血清CysC和RBP对检测肿瘤化疗患者早期肾损伤具有较高的临床应用价值。     

Retinol Binding Protein

Introduction: Burn injury leads to vast changes in both metabolic and inflammatory responses and is associated with increased morbidity and mortality. Insulin resistance (IR) and hyperglycemia are major components of the hypermetabolic response found in burn‐injured patients and subsequently contribute to adverse outcomes. Studies have shown that increased systemic retinol binding protein (RBP) levels are associated with IR and hyperinflammation in diabetic and obese patients. The aim of this study was to determine RBP profiles and to test the hypothesis that elevated RBP levels are associated with both IR and the inflammatory response in burned patients. Methods: RBP was measured in 372 patients during the acute stay postburn. Patients' demographics, glucose levels, and insulin administration were recorded. Cytokines, hormones, plasma proteins, and organ markers were measured. The average of all measurements of RBP (2.1 mg/dL) was used to divide patients into high and low groups. Statistical analysis was performed by Student t test. Statistical significance was accepted at P < .05. Results: Fifty‐one patients (high group) had elevated RBP levels during acute hospitalization and demonstrated a significant higher incidence of multiorgan failure, sepsis, and mortality (P < .05). Moreover, in the high group, a significant increase of IR, inflammatory cytokines, and catabolic and organ‐specific markers were detected (P < .05). Conclusions: Increased RBP levels postburn correlate with increased IR, inflammatory and catabolic responses, incidence of multiorgan failure, and mortality. RBP may be a novel biomarker to monitor these detrimental responses postburn.     

铅接触人群β2-MG、NAG、RBP值的变化观察

目的 研究接铅工人β2 - MG、NAG、RBP的变化.方法 采用分组比较与各指标增高人数分布描述法.结果 接铅组β2 - MG、NAG、RBP比对照组增高2倍以上.按接铅工龄分组分析,有随着接铅工龄延长而增高的趋势;分组比较,除了ZPP仅在1～2年组与5～6年组间有明显差别之外,其他指标在1～2年组与3～4、5～6年组间均有明显差别;但各指标在3～4年组与5～6年组间均无明显差别.按pbB值分组分析,有随着血铅值增高而增高的趋势;分组比较,除了NAG在各组间无差别之外,其他指标在＜400组与400 ～ 600组、＞600组间均有明显差别;在400 ～ 600组与＞ 600组间比较,除了ZPP之外,其他指标在两组间均有明显差别.分析接铅组β2 - MG、NAG、RBP的增高人数,各以56.59、72.35、57.23％分布于3倍对照均值组.结论 β2 - MG、NAG、RBP值的变化与接铅工龄和血铅值有一定关系,并且3指标增高人数的集中分布趋势较pbB、ZPP明显.     

运动对糖尿病肾病早期相关指标的影响

目的研究运动对糖尿病肾病(DN)早期诊断指标如尿微量白蛋白(Alb)、尿转铁蛋白(TRF)、尿铜蓝蛋白(CP)、尿视黄醇结合蛋白(RBP)的影响。方法对45名2型糖尿病患者做次极量运动试验,运动前后分别测尿Alb、尿TRF、尿CP、尿RBP及尿肌酐(Cr),并以26名非糖尿病人做对照。结果糖尿病患者运动后尿Alb/Cr较运动前增加(P>0.01),尿TRF/Cr,CP/Cr,RBP/Cr运动前后无明显改变;非糖尿病人运动后尿Alb/Cr也较运动前增加(P>0.05),尿TRF/Cr,CP/Cr,RBP/Cr运动前后也无明显改变。而在相关分析中发现,尿RBP/Cr与Alb/Cr无显著相关性。尿TRF/Cr,CP/Cr与Alb/Cr有显著相关性。结论尿Alb/Cr受运动影响而尿TRF/Cr、CP/Cr不受运动影响,可作为DN早期诊断指标之一。     

RBP2在肿瘤中的作用及其选择性抑制剂的研究进展

视黄醇结合蛋白2（retinol-binding protein 2，RBP2）可特异性去除组蛋白H3第4位赖氨酸上的二甲基和三甲基，从而介导基因沉默和调节细胞功能。多项研究表明RBP2与肿瘤的关系密切，它不仅有助于肿瘤细胞的分化、代谢和增殖，还可以阻遏肿瘤细胞抑制基因的表达，诱发肿瘤细胞的侵袭和转移，促进耐药的发生。因此，RBP2可成为肿瘤诊断和治疗的新靶点之一。针对RBP2的选择性抑制剂的探讨将有助于我们对其结构、功能及生物学作用的认识，并有望开发出新的抗癌药物。     

Correlation between serum Dickkopf-1 (DKK1) levels and coronary artery stenosis

Background and aimsTo study the correlation between the level of serum Dickkopf-1 (DKK1) and the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease.Methods and resultsIn 2018, general data and biochemical indexes of 311 patients who underwent coronary angiography were recorded. Before procedure, arterial blood was drawn and the concentrations of DKK1, retinol binding protein 4 (RBP4), plasminogen activator inhibitor (PAI-1) were measured. Based on coronary angiography results, subjects were divided into a coronary heart disease (CHD) group; and a non-coronary heart disease (non-CHD)group. The CHD group was divided into three subgroups: the low Gensini score; the middle Gensini score; and the high Gensini score subgroups. Compared with those of the non-CHD group, DKK1, RBP4 and PAI-1 of the CHD group were significantly higher, while the OC was lower.DKK1,RBP4 and PAI-1 levels of the middle and high Gensini subgroups were significantly higher, compared with that of the low Gensini subgroup. Differences between osteocalcin (OC), beta-isomerized C-terminal telopeptidase (β-CTX), and 25(OH)₂D₃ of the three subgroups were not significant.Correlation between DKK1 and the inflammatory factors, RBP4 and PAI-1, was positive. Correlation between DKK1 and β - CTX, 25(OH)₂D₃ and OC was not significant. DKK1 was a risk factor for CHD. The degree of coronary artery stenosis was related to DKK1 concentration.ConclusionsSerum DKK1 levels in coronary heart disease patients were significantly higher, and positively correlated with the degree of coronary artery stenosis. DKK1 level is an independent risk factor for coronary heart disease.     

De-novo “germline second hit” loss-of-heterozygosity RBP3 deletion mutation causing recessive high myopia

Knudson's “two hit” hypothesis, mostly associated with cancer, relates to a primary heterozygous germline mutation complemented by a somatic mutation in the second allele. When the somatic “second hit” is a deletion mutation, the heterozygosity due to the first hit is lost (“loss of heterozygosity”). As the rate of germline mutations is almost two orders of magnitude lower than that of somatic mutations, de-novo germline mutations causing autosomal recessive diseases in carriers of inherited heterozygous mutations are not common. We delineate a case of high myopia presenting at infancy with mild diminution of retinal responses. Exome sequencing identified a paternally inherited apparently homozygous missense mutation in RBP3. Chromosomal microarrays delineated a de-novo germline heterozygous deletion encompassing RBP3, verified through revision of WES data. Thus, we demonstrate an inherited RBP3 missense mutation complemented by a de-novo germline RBP3 deletion, causing loss of heterozygosity of the inherited mutation. We describe a novel RBP3 missense mutation, report the first isolated RBP3 deletion, and demonstrate infantile high myopia as an initial presentation of RBP3 disease. Notably, we highlight de-novo germline deletion mutations causing “loss of heterozygosity” of inherited heterozygous mutations, culminating in autosomal recessive diseases, and discuss the scarce literature.     

Development and validation of a nomogram for the prediction of brain metastases in small cell lung cancer

Introduction

The aim was to develop and validate a nomogram for the prediction of brain metastases (BM) in small cell lung cancer (SCLC), to explore the risk factors and assist clinical decision-making.

Methods

We reviewed the clinical data of SCLC patients between 2015 and 2021. Patients between 2015 and 2019 were included to develop, whereas patients between 2020 and 2021 were used for external validation. Clinical indices were analysed by using the least absolute shrinkage and selection operator (LASSO) logistic regression analyses. The final nomogram was constructed and validated by bootstrap resampling.

Results

A total of 631 SCLC patients between 2015 and 2019 were included to construct model. Gender, T stage, N stage, Eastern Cooperative Oncology Group (ECOG), haemoglobin (HGB), the absolute value of lymphocyte (LYMPH #), platelet (PLT), retinol-binding protein (RBP), carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were identified as risk factors and included into the model. The C-indices were 0.830 and 0.788 in the internal validation by 1000 bootstrap resamples. The calibration plot revealed excellent agreement between the predicted and the actual probability. Decision curve analysis (DCA) showed better net benefits with a wider range of threshold probability (net clinical benefit was 1%–58%). The model was further externally validated in patients between 2020 and 2021 with a C-index of 0.818.

Conclusions

We developed and validated a nomogram to predict the risk of BM in SCLC patients, which could help clinicians to rationally schedule follow-ups and promptly implement interventions.