缺血性脑卒中后脑脊液循环障碍及其意义

缺血性脑卒中(AIS)是最常见的卒中亚型。研究显示,AIS之后会引起颅内压(ICP)升高,从而导致CSF循环障碍影响神经功能。AIS后CSF的分泌、转运和交换以及淋巴引流都可能影响CSF循环障碍的形成。目前并没有直接的证据提示在AIS后CSF分泌增加。胶质淋巴通路(GS)是中枢神经系统独特的CSF转运和交换通路,AIS后可出现CSF在脑实质流入、流出、和组织间液(ISF)进行物质交换受阻、以及血管周围间隙(PVS)淤塞等异常,导致脑代谢废物清除率降低以及毒性产物的沉积。AIS之后机体可能通过代偿性淋巴管增生来促进ISF和CSF的引流,从而减轻CSF循环障碍带来的损害。AIS后GS的功能障碍以及相应的CSF循环障碍可能是脑卒中再发、淀粉样蛋白Aβ沉积和认知障碍的关键病理生理途径,AIS后CSF循环障碍值得进一步研究。

CT Perfusion Imaging Predicts One-Month Outcome in Patients with Acute Spontaneous Hypertensive Intracerebral Hemorrhage

Purpose: Little is known about the relationship between perihematomal perfusion parameters in acute spontaneous hypertensive intracerebral hemorrhage patients and recent outcome. The purpose of this study was to evaluate the relationship between the perfusion parameters of the perihematomal brain tissue and the recent prognosis of patients with acute spontaneous hypertensive intracerebral hemorrhage (shICH) using CT perfusion (CTP) imaging. Methods: Twenty-six patients with clinical and CT diagnosed supratentorial shICH received CTP scanning within 8 - 19 h after symptom onset. At the maximum levels of the hematoma, cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of perihematomal area (isodense within 1cm rim of perilesion area on plain CT) and contralateral mirrored hemisphere were measured, and rCBF, rCBV, rMTT were calculated (ipsilateral/contralateral). The one-month follow-up in accordance with daily living table (Barthel index, BI) by telephone was recorded. Results: The CBV, CBF, and MTT values of perihematoma area were (1.61 ± 1.53) ml·100 g-1, (16.48 ± 12.58) ml·100 g-1·min-1, and (9.12 ± 2.57) s, respectively. (For more information,please refer to the PDF)

Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Herein,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical responses.The multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in PCa.Through the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary cells.We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations.Surprisingly,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model.Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells

Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future.

Synergistic effect of vermiculite and submerged plants on lake sediments

The synergistic effect of vermiculite and the submerged macrophytes Vallisneria spiralis and Hydrilla verticillata on lake sediment was studied using diffusive gradients in thin films(DGT)technology.The dynamics of phosphorus(P)fractions in sediment,the labile-P and labile-S in the water-sediment continuum,and the microbial community in the rhizosphere were studied.Vermiculite effectively promoted reproduction of microorganisms in the sediments Microbial abundance in treatments containing V.spiralis with sediments containing 10%added vermiculite,and H.verticillata containing 50%added vermiculite being 1.7 and 3.5 times higher than the controls which contained no added vermiculite.Acidobacteria and Proteobacteria populations,which are both beneficial for the sediment microenvironment,were higher in treatment groups containing vermiculite.The bioavailable-P in treatment groups containing added vermiculite was lower at the sediment-water interface,with a correlating decrease of TP by between 63%and 91%in the overlying water.This suggests that vermiculite can affect the release of labile P and facilitate the assimilation of nutrients by macrophyte roots.Additionally,vermiculite can improve the Oxidation-Reduction potential and further reduce sulfide toxicity to plants.These results provide theoretical guidance and technical support for the application of vermiculite combined with submerged plants for the remediation of eutrophic lakes.

抗TNFα抗体Fab片段在大肠杆菌内表达的优化

[目的]筛选在大肠杆菌内对抗TNFα抗体Fab片段转运效率最高的信号肽,并优化Fab片段表达的培养条件。[方法]通过对抗TNFα抗体Fab片段连接不同的信号肽序列获得了5种分泌载体并完成了重组蛋白的表达,通过Westen Blot检测蛋白表达情况并筛选出最适信号肽,通过正交试验优化了培养条件。[结果]对周质重组蛋白抗TNFα抗体Fab片段转运效率最高的信号肽为麦芽糖结合蛋白MalE,周质重组蛋白的最佳诱导条件为温度29℃、时间9 h、p H7. 5、IPTG浓度2. 0 mmol/L。[结论]通过信号肽筛选和培养条件优化,促进了菌体对周质重组蛋白抗TNFα抗体Fab片段的表达,其中最佳信号肽MalE对目的蛋白的相对表达量为1. 3。