Combining Serum Cystatin C with Total Bilirubin Improves Short-Term Mortality Prediction in Patients with HBV-Related Acute-On-Chronic Liver Failure

Background & Aims

HBV-related acute-on-chronic liver failure (HBV-ACLF) is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF.

Methods

Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of the variates for early predicting mortality.

Results

Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7%) during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC) and total bilirubin (TBil) were independent factors significantly (P < 0.01) associated with survival. Our results further showed that new prognostic index (PI) combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr). The survival rate in low risk group (PI < 3.91) was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91) (17.4%, P < 0.001).

Conclusion

We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.     

Detecting Static and Dynamic Differences between Eyes-Closed and Eyes-Open Resting States Using ASL and BOLD fMRI

Resting-state fMRI studies have increasingly focused on multi-contrast techniques, such as BOLD and ASL imaging. However, these techniques may reveal different aspects of brain activity (e.g., static vs. dynamic), and little is known about the similarity or disparity of these techniques in detecting resting-state brain activity. It is therefore important to assess the static and dynamic characteristics of these fMRI techniques to guide future applications. Here we acquired fMRI data while subjects were in eyes-closed (EC) and eyes-open (EO) states, using both ASL and BOLD techniques, at two research centers (NIDA and HNU). Static brain activity was calculated as voxel-wise mean cerebral blood flow (CBF) using ASL, i.e., CBF-mean, while dynamic activity was measured by the amplitude of low frequency fluctuations (ALFF) of BOLD, i.e., BOLD-ALFF, at both NIDA and HNU, and CBF, i.e., CBF-ALFF, at NIDA. We showed that mean CBF was lower under EC than EO in the primary visual cortex, while BOLD-ALFF was higher under EC in the primary somatosensory cortices extending to the primary auditory cortices and lower in the lateral occipital area. Interestingly, mean CBF and BOLD-ALFF results overlapped at the visual cortex to a very small degree. Importantly, these findings were largely replicated by the HNU dataset. State differences found by CBF-ALFF were located in the primary auditory cortices, which were generally a subset of BOLD-ALFF and showed no spatial overlap with CBF-mean. In conclusion, static brain activity measured by mean CBF and dynamic brain activity measured by BOLD- and CBF-ALFF may reflect different aspects of resting-state brain activity and a combination of ASL and BOLD may provide complementary information on the biophysical and physiological processes of the brain.     

Individual Variability and Test-Retest Reliability Revealed by Ten Repeated Resting-State Brain Scans over One Month

Individual differences in mind and behavior are believed to reflect the functional variability of the human brain. Due to the lack of a large-scale longitudinal dataset, the full landscape of variability within and between individual functional connectomes is largely unknown. We collected 300 resting-state functional magnetic resonance imaging (rfMRI) datasets from 30 healthy participants who were scanned every three days for one month. With these data, both intra- and inter-individual variability of six common rfMRI metrics, as well as their test-retest reliability, were estimated across multiple spatial scales. Global metrics were more dynamic than local regional metrics. Cognitive components involving working memory, inhibition, attention, language and related neural networks exhibited high intra-individual variability. In contrast, inter-individual variability demonstrated a more complex picture across the multiple scales of metrics. Limbic, default, frontoparietal and visual networks and their related cognitive components were more differentiable than somatomotor and attention networks across the participants. Analyzing both intra- and inter-individual variability revealed a set of high-resolution maps on test-retest reliability of the multi-scale connectomic metrics. These findings represent the first collection of individual differences in multi-scale and multi-metric characterization of the human functional connectomes in-vivo, serving as normal references for the field to guide the use of common functional metrics in rfMRI-based applications.     

Long-Term Effect of Crop Rotation and Fertilisation on Bioavailability and Fractionation of Copper in Soil on the Loess Plateau in Northwest China

The bioavailability and fractionation of Cu reflect its deliverability in soil. Little research has investigated Cu supply to crops in soil under long-term rotation and fertilisation on the Loess Plateau. A field experiment was conducted in randomized complete block design to determine the bioavailability and distribution of Cu fractions in a Heilu soil (Calcaric Regosol) after 18 years of rotation and fertilisation. The experiment started in 1984, including five cropping systems (fallow control, alfalfa cropping, maize cropping, winter wheat cropping, and grain-legume rotation of pea/winter wheat/winter wheat + millet) and five fertiliser treatments (unfertilised control, N, P, N + P, and N + P + manure). Soil samples were collected in 2002 for chemical analysis. Available Cu was assessed by diethylene triamine pentaacetic acid (DTPA) extraction, and Cu was fractionated by sequential extraction. Results showed that DTPA-Cu was lower in cropping systems compared with fallow control. Application of fertilisers resulted in no remarkable changes in DTPA-Cu compared with unfertilised control. Correlation and path analyses revealed that soil pH and CaCO₃ directly affected Cu bioavailability, whereas available P indirectly affected Cu bioavailability. The concentrations of Cu fractions (carbonate and Fe/Al oxides) in the plough layer were lower in cropping systems, while the values in the plough sole were higher under grain-legume rotation relative to fallow control. Manure with NP fertiliser increased Cu fractions bound to organic matter and minerals in the plough layer, and its effects in the plough sole varied with cropping systems. The direct sources (organic-matter-bound fraction and carbonate-bound fraction) of available Cu contributed much to Cu bioavailability. The mineral-bound fraction of Cu acted as an indicator of Cu supply potential in the soil.     

Recoverin depletion accelerates cone photoresponse recovery

The neuronal Ca²⁺-binding protein Recoverin has been shown to regulate phototransduction termination in mammalian rods. Here we identify four recoverin genes in the zebrafish genome, rcv1a, rcv1b, rcv2a and rcv2b, and investigate their role in modulating the cone phototransduction cascade. While Recoverin-1b is only found in the adult retina, the other Recoverins are expressed throughout development in all four cone types, except Recoverin-1a, which is expressed only in rods and UV cones. Applying a double flash electroretinogram (ERG) paradigm, downregulation of Recoverin-2a or 2b accelerates cone photoresponse recovery, albeit at different light intensities. Exclusive recording from UV cones via spectral ERG reveals that knockdown of Recoverin-1a alone has no effect, but Recoverin-1a/2a double-knockdowns showed an even shorter recovery time than Recoverin-2a-deficient larvae. We also showed that UV cone photoresponse kinetics depend on Recoverin-2a function via cone-specific kinase Grk7a. This is the first in vivo study demonstrating that cone opsin deactivation kinetics determine overall photoresponse shut off kinetics.     

Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats

Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.     

结核分枝杆菌ABC转运蛋白与物质的跨膜转运

结核分枝杆菌作为一种胞内寄生菌,主要存在于巨噬细胞吞噬体内,并且通过与宿主细胞竞争摄取营养物质、主动排出有毒物质来维持生存。因此,参与上述过程的ABC转运蛋白在结核分枝杆菌的致病中发挥着举足轻重的作用。已有报道结核分枝杆菌基因组编码了38个ABC转运蛋白。这类蛋白质有着广泛的底物结合谱,参与了无机离子、糖类、氨基酸、寡肽、药物等多种物质的跨膜转运。本文将对结核分枝杆菌编码的ABC转运蛋白超家族中的不同成员及其底物特异性、转运机制以及与毒力的关系的研究进展进行综述。     

过表达pps基因和aroG~(fbr)基因对北京棒杆菌L-色氨酸合成的影响

【目的】通过增加北京棒杆菌(Corynebacterium pekinense)PD-67芳香族氨基酸合成的前体物质磷酸烯醇式丙酮酸(PEP)的供应,解除终产物对芳香族氨基酸合成途径中第一个酶同时也是关键酶3-脱氧-D-阿拉伯庚酮糖-7-磷酸合酶(DS)的反馈抑制并提高抗反馈抑制的DS的活力,使碳流更多地流向芳香族氨基酸合成途径,从而积累更多L-色氨酸。【方法】运用PCR技术扩增北京棒杆菌PD-67磷酸烯醇式丙酮酸合酶基因pps,与表达载体连接构建重组质粒pXPS;运用重叠PCR技术定点突变大肠杆菌(Escherichia coli)受苯丙氨酸调控的DS基因aroG,使相应的编码氨基酸序列发生突变:Leu175Asp,新的基因命名为aroGfbr,与表达载体连接构建重组质粒pXA;构建pps和aroGfbr的共表达重组质粒pXAPS。将3个重组质粒分别转入菌株PD-67,构建工程菌株PD-67/pXPS、PD-67/pXA和PD-67/pXAPS。通过摇瓶发酵研究工程菌株的发酵特性。【结果】酶活分析结果表明,pps基因和aroGfbr基因在北京棒杆菌PD-67中均实现了表达。工程菌株PD-67/pXA粗酶液DS抗反馈抑制分析表明,AroGfbr已解除酪氨酸和苯丙氨酸的反馈抑制。过表达pps基因和aroGfbr基因分别使工程菌L-色氨酸产量提高12.1%和26.8%,双基因共表达可使工程菌的产酸量提高35.9%。【结论】北京棒杆菌PD-67pps基因的过表达以及大肠杆菌来源的解除反馈抑制的aroGfbr的过表达均有助于增加PD-67 L-色氨酸的合成,而双基因的共表达可以进一步提高L-色氨酸的积累量。     

Highly selective screening of the bioactive compounds in Huoxue capsule using immobilized β2-adrenoceptor affinity chromatography

A highly selective assay was developed for screening compounds that bind to the porcine recombinant β₂-adrenoceptor (β₂-AR) with affinity chromatography coupled to quadrupole time-of-flight mass spectrometry (Q-TOF–MS). The methodology involved selective screening with immobilized β₂-AR, a highly accurate identification via Q-TOF–MS, and a functional evaluation of the screened compounds with a sensitive myograph system. Ferulic acid, hydroxysafflor yellow A (HSYA), and naringin were confirmed to be the bioactive compounds in Huoxue capsule that specifically bound to the β₂-AR. These compounds produced a concentration-dependent relaxation of arteries that were contracted by treatment with phenylephrine, and the relaxation caused by these compounds was attenuated in the presence of ICI 118551, a type of β₂-AR antagonist. Our data indicate that the use of an immobilized receptor is potentially an alternative method for the rapid screening of bioactive compounds in a complex matrix because of its high specificity. β₂-AR affinity chromatography was valuable in focusing attention on the further investigation of ferulic acid, HSYA, and naringin as β₂-AR agonists.     

HepG2.2.15 as a model for studying cell protrusion and migration regulated by S100 proteins

Much of the difficulty in elucidating the precise function of S100 protein family has been attributed to functional redundancy and compensation by its conserved family members. In this study, we showed that seven S100 family members were almost totally undetectable in HepG2.2.15 cells, while all of them were highly expressed in its parental HepG2 cells. Re-expression of S100 proteins in HepG2.2.15 cells can partially rescue their defects in cell protrusion and migration through the regulation of cytoskeletons and adhesions. Thus, HepG2.2.15 can serve as a useful model for studying cell protrusion and migration regulated by S100 proteins.