益肝康等活血化瘀中药抑制IL-1β刺激的HSC增殖及TIMP-1的表达

目的:探讨活血化瘀中药益肝康、丹参小复方、丹参对IL-1β刺激的活化的大鼠肝星状细胞(HSCs)增殖及基质金属蛋白酶抑制因子 mRNA(TIMP mRNA)表达的影响．方法:体外培养活化的大鼠HSC,随机分为8 组:对照组(A组)、IL-1β 10 μg/L(B组)、IL- 1β 10μg/L 益肝康2 g/L干预组(C组)、IL- 1β 10 μg/L 丹参小复方2g/L干预组(D组)、 IL-1β 10μg/L 丹参2g/L干预组(E组)、丹参 2 g／L(F组)、丹参小复方2 g/L(G组)、益肝康 2 g／L(H组)．加药后24 h．应用活细胞计数试剂盒-CCK-8检测各组HSC增殖,采用半定量 RT-PCR方法检测各组HSC TIMP-1 mRNA的表达．结果:A组HSC增殖和TIMP-1 mRNA表达强于F、G、H组(1．291±0．09 vs 1．055±0．105, 1±0．07,0．883±0．06,P<0．01:0．591±0．064 vs 0．493±0．088．0．458±0．076．0．356±0．046． P<0．05或P<0．01);H组HSC增殖和TIMP-1 mRNA表达低于F组和G组(P<0．05);B组HSC 增殖和TIMP-1 mRNA表达均明显强于A组 (1．575±0．017 vs 1.291±0,09,P<0．01;1．369± 0．097 vs 0．591±0．064,P<0．01)和C、D、E组 (1．575±0．017 vs 0．906±0．09,1．015±0．081, 1．097±0．038,P<0．01;1．369±0．097 vs 0．694 ±0．078,0．854±0．05,0．898±0．12,P<0．01);C 组HSC增殖和TIMP-1 mRNA表达低于D组和 E组(P<0．05)．结论:益肝康等活血化瘀中药能抑制IL-1β刺激的HSCs增殖及TIMP-1 mRNA表达,发挥其抗肝纤维化功效．益肝康抗肝纤维化作用强于丹参小复方和丹参单药．     

缺血性脑卒中后血管性认知功能障碍患者相关因素分析

目的探讨缺血性脑卒中后血管性认知功能障碍(VCI)发生的相关因素。方法收集2011年6月至2014年6月入住我院的208例缺血性脑卒中患者的临床资料,其中并发VCI患者82例,非VCI(NVCI)患者126例。分别采用Pearson单因素与多元Logistic回归分析的方法对缺血性脑卒中后并发VCI的相关因素加以确定。结果 (1)经Pearson单因素分析,VCI组与NVCI组在高血压、房颤、血脂异常、NIHSS评分、高糖化血红蛋白、同型半胱氨酸、超敏C反应蛋白及关键部位病灶差异具有统计学意义(P<0.05,P<0.01);(2)经多元Logistic回归分析,影响缺血性脑卒中后VCI的相关因素包括:高糖化血红蛋白(β=1.928,SE=0.382,Wald=6.928,P<0.05,OR值=2.559,95%CI为1.544~5.782)、高血压(β=2.024,SE=0.195,Wald=7.125,P<0.01,OR值=2.135,95%CI为1.672~3.225)、高同型半胱氨酸(β=2.359,SE=0.297,Wald=8.567,P<0.01,OR值=2.687,95%CI为1.938~4.253)、关键部位病灶(β=2.346,SE=0.597,Wald=7.259,P<0.05,OR值=2.187,95%CI为1.692~3.876)及高超敏C反应蛋白(β=1.856,SE=0.118,Wald=5.358,P<0.05,OR值=2.102,95%CI为1.432~3.870)。结论 影响缺血性脑卒中后并发VCI的因素较多,应对这些危险因素进行早期干预,降低缺血性脑卒中后VCI的发病率。     

按三级学科方向培养手术室专科护士可行性的调查

目的：了解不同等级医院对手术室专科护士的需求,探索能满足不同等级医院手术室护理工作实际需求的专科护士培训方案。方法自行设计调查表,选择在江苏省手术室专科护士培训基地学习的80名手术室护士进行调查。调查内容包括一般资料、所在医院三级学科和亚专业学科细化情况、参加专科护士培训后工作状况、手术室专科护士的培养模式和按照三级学科培养手术室专科护士的实施方案4个方面。结果80名护士均认为有必要开展手术室专科护士培训,80．00％的人认为目前模式属手术室全科护士的培训;72．22％的二级医院的护士认为参加培训学习的理论知识、参加的临床实践技能能满足工作需要,可继续采取目前培养模式;74．19％的三级医院的护士认为培训知识尚能满足工作需要,但针对自己的三级学科方向还不够强、不够细,应该按照三级学科培养手术室专科护士。结论根据不同等级医院手术室护理工作的实际需求,建立统一招生、同步培训、分层培养的统分结合培养模式,能培养适应不同等级医院手术室需求的专科护士。     

Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit’s width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons’ activities and help reveal the potential functional connections in the whole zebrafish’s brain.OCIS codes: (180.2520) Fluorescence microscopy, (110.0110) Imaging systems, (170.3880) Medical and biological imaging, (170.2945) Illumination design, (180.1790) Confocal microscopy     

Placental genomic risk scores and early neurodevelopmental outcomes

Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792–801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia’s PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.

Understanding the deviations from normal trajectories of brain development may be crucial for predicting illness and for prevention. Epidemiological studies have consistently identified early antecedents, including complications during pregnancy (1–4) and delays in developmental milestones (5–8). The incidence of many developmental disorders tends to be higher in males (9), and risk is typically highly heritable (10). While rare and moderately penetrant genetic variations account for a minority of cases, genome-wide association studies (GWASs) show that most risk is attributable to common variants across the genome (11, 12). Genomic risk scores (GRSs) from GWASs allow a much greater prediction of liability of the disorder than single common variant genotypes, but GRSs per se are not useful in predicting individual risk (13).We previously identified an environmental context in early life in which genomic risk for schizophrenia may enhance disease susceptibility (14). We found that the liability of schizophrenia explained by genomic risk (that is, schizophrenia GRS, also referred to as polygenic risk score; PRS) was more than five times higher in individuals with a history of obstetrical complications (here, early-life complications; ELCs; i.e., during pregnancy, at labor/delivery, and early in neonatal life) compared with its absence (14). Such interaction was exclusive of the GRSs constructed from the loci with the most significant associations with schizophrenia (GRS1: GWAS P < 5 × 10⁻⁸; GRS2: GWAS P < 1 × 10⁻⁶). Genes in the GRS1 and GRS2 loci were more highly expressed in placental tissue compared with genes in GWAS loci not interacting with ELCs (GRS3 to 10); they were up-regulated in placentae from complicated pregnancies and strongly correlated within placenta with expression of immune response genes (14), consistent with previous evidence linking placenta, inflammation, and brain development (15, 16).To investigate the role of placenta biology in the interaction between schizophrenia GRSs and ELCs, we derived sets of GRSs based on single-nucleotide polymorphisms (SNPs) marking schizophrenia-GWAS loci containing genes highly expressed in placenta and differentially expressed in placentae from complicated compared with normal pregnancies (PlacGRSs; placental genomic risk scores) and also from the remaining GWAS loci (NonPlacGRSs; nonplacental genomic risk scores). We found that only PlacGRSs interacted with ELCs on schizophrenia-case control status, while NonPlacGRSs did not, implicating genes involved in placenta stress as driving the interaction between genomic risk and ELCs. These interactions were specifically related to placental gene expression, in that they were not detected when calculating GRSs based on SNPs marking loci highly expressed or epigenetically regulated in other tissues, including various adult and fetal tissues/embryonic cells, and fetal brain. Finally, we detected a much stronger enrichment of expression of the schizophrenia-risk genes in placentae from male compared with female offspring, suggesting a role of placenta in the higher incidence of schizophrenia in males (14).We here investigate whether placental genomic risk for schizophrenia as well as several other developmental disorders and traits is linked with early neurodevelopmental outcomes in individuals with a history of ELCs associated with placenta pathophysiology. Abundant evidence shows that ELCs have implications for early developmental trajectories, including brain size, intellectual development, and neuromotor function as well as for schizophrenia later in life (3, 5, 17–19). Based on these prior observations and our earlier findings (14), we hypothesized that schizophrenia PlacGRSs, in contrast to NonPlacGRSs, have a negative effect on early developmental outcomes, especially in males. Further consistent with our earlier findings, we hypothesized that this negative relationship is characteristic of the PlacGRSs constructed from the placental schizophrenia-GWAS loci with the strongest association with the disorder (PlacGRS1: GWAS P < 5 × 10⁻⁸; PlacGRS2: GWAS P < 1 × 10⁻⁶). We studied the relationship of PlacGRSs and NonPlacGRSs with brain volume in a unique sample of neonates who underwent MRI scanning shortly after birth, and analyzed the relationship with neurocognitive development at 1 and 2 y of age in the same subjects. Finally, we analyzed the relationship of PlacGRSs and NonPlacGRSs with brain volume in a sample of adult controls and patients with schizophrenia.     

The Effect of Glycated Hemoglobin and Albumin-Corrected Glycated Serum Protein on Mortality in Diabetic Patients Receiving Continuous Peritoneal Dialysis

♦ Objective:

To explore the effect of glycated hemoglobin (HbA1c) and albumin-corrected glycated serum proteins (Alb-GSP) on the mortality of diabetic patients receiving continuous peritoneal dialysis (PD).

♦ Methods:

In this single-center retrospective cohort study, incident diabetic PD patients from January 1, 2006, to December 31, 2010, were recruited, and followed up until December 31, 2011. The effect of HbA1c and Alb-GSP on mortality was evaluated by Cox proportional hazards models.

♦ Results:

A total of 200 patients (60% male, mean age 60.3 ± 10.6 years) with a mean follow-up of 29.0 months (range: 4.3 – 71.5 months) were recruited. Sixty-four patients died during the follow-up period, of whom 21 died of cardiovascular disease (CVD). Mean values for HbA1c, GSP and Alb-GSP were 6.7% (range: 4.1 – 12.5%), 202 μmol/L (range: 69 – 459 μmol/L), and 5.78 μmol/g (range: 2.16 – 14.98 μmol/g), respectively. The concentrations of GSP and Alb-GSP were closely correlated with HbA1c (r = 0.41, p < 0.001 and r = 0.45, p < 0.001, respectively). In multivariate Cox proportional hazards models, patients with HbA1c ≥ 8% were associated with increased risk of all-cause mortality (hazard ratio [HR] = 2.29, 95% confidence interval [CI]: 1.06 – 4.96, p = 0.04), but no increased mortality in patients with 6.0% ≤ HbA1c ≤ 7.9%. Patients with Alb-GSP ≤ 4.50 μmol/g had increased all-cause and non-cardiovascular mortality (HR = 2.42, 95% CI: 1.13 – 5.19, p = 0.02; and HR = 2.98, 95% CI: 1.05 – 8.48, p = 0.04 respectively).

♦ Conclusions:

Increased HbA1c and decreased Alb-GSP may be associated with poorer survival in diabetic PD patients, with a non-significant trend observed for poorer survival with the highest level of Alb-GSP.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.     

结肠癌多药耐药机制的研究进展

结肠癌是人类常见的消化道恶性肿瘤,化学治疗在该病的综合治疗中起着重要的作用,但结肠癌细胞对化学治疗药物的多药耐药性(MDR)严重影响了患者的化学治疗效果。MDR是指肿瘤细胞对一种化学治疗药物具有耐药性的同时,对其他结构不同、作用靶点不同的抗肿瘤药物也具有耐药性的现象。结肠癌的MDR机制除了以往研究较多的ATP结合转运蛋白的高表达、耐药相关酶表达的改变外,近年来发现,ATP转运蛋白的单核苷酸多态性、抗细胞凋亡蛋白的表达及结肠癌干细胞等均与结肠癌细胞的MDR密切相关。该文对近年来结肠癌MDR机制的研究进展进行阐述。