p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3

p190RhoGAP and Rho are key regulators of oligodendrocyte differentiation. The gene encoding p190RhoGAP is located at 19q13.3 of the human chromosome, a locus that is deleted in 50%-80% of oligodendrogliomas. Here we provide evidence that p190RhoGAP may suppress gliomagenesis by inducing a differentiated glial phenotype. Using a cell culture model of autocrine loop PDGF stimulation, we show that reduced Rho activity via p190RhoGAP overexpression or Rho kinase inhibition induced cellular process extension, a block in proliferation, and reduced expression of the neural precursor marker nestin. In vivo infection of mice with retrovirus expressing PDGF and the p190 GAP domain caused a decreased incidence of oligodendrogliomas compared with that observed with PDGF alone. Independent experiments revealed that the retroviral vector insertion site in 3 of 50 PDGF-induced gliomas was within the p190RhoGAP gene. This evidence strongly suggests that p190 regulates critical components of PDGF oncogenesis and can act as a tumor suppressor in PDGF-induced gliomas by down-regulating Rho activity.     

Can Swimming Microalgal Cells be Vehicles for ZnO Nanoparticle Transportation and Thus Lead to Zn Diffusion?

The concentration of eco-toxic zinc oxide nanoparticles (nZnO) in aquatic ecosystems is increasing, and an effective method for their removal is needed. We hypothesize that microalgal cells may act as nZnO vehicles—if the nZnO concentration does not affect their swimming ability—enabling Zn diffusion and sedimentation. We conducted experiments using flasks connected via a U-type vessel; the first flask contained nZnO suspensions and second flask contained artificial seawater, respectively. We added microalgae to the first flask and illuminated the second. The microalgae appeared to promote sedimentation. However, only a few microalgal cells passed via phototaxis into the second flask, so the detection of nZnO or Zn ions in the second flask was not possible. Therefore, to confirm whether the microalgae affect Zn transportation, a more accurate method to detect nZnO or Zn ions at very low concentrations is needed.

     

58例双瓣替换术体外循环管理体会

目的：回顾５８例双瓣替换术体外循环管理状况,总结双瓣替换术中灌注技术。方法：对５８例风湿性心脏瓣膜病人施行二尖瓣、主动脉瓣替换术中体外循环手术的临床资料、心肺转汉方法和心肌保护中的难点及处理进行回顾总结分析。结果：５８例中早期死亡２例,死亡率３．４５％Ｒ。结论：只有良好的体外循环灌注技术和心肌保护,才能保证双瓣替换术病人顺利渡过围术期,降低手术死亡率。     

Engineering substrate promiscuity in 2,4-dichlorophenol hydroxylase by in silico design

2,4-Dichlorophenol hydroxylase (2,4-DCP hydroxylase) is a key enzyme in the degradation of 2,4-dichlorophenoxyacetic acid in the hydroxylation step in many bacteria. Our previous study demonstrated that a 2,4-DCP hydroxylase (TfdB-JLU) exhibits broad substrate specificity for chlorophenols (CPs) and their homologues. In this study, TfdB-JLU has been engineered by rational design to further broaden its substrate scope towards CPs. We dissect the architectures of enzymes from oxidoreductase families to discover their underlying structural sources of substrate promiscuity. A homology model of TfdB-JLU has been built and docking experiments of this homology model with its natural substrate 2,4-DCP reveal that the phenyl rings of 2,4-DCP form strong interactions with residues His47, Ile48, Trp222, Pro316, and Phe424. These residues are found to be important for substrate binding in the active site. Then, the site-directed mutagenesis strategy has been applied for redesigning substrate promiscuity in TfdB-JLU. The TfdB-JLU-P316Q variant obtained shows a significant enhancement of activity (up to 3.4-fold) toward 10 CP congeners compared to wild-type TfdB-JLU. Interestingly, the active improvements of TfdB-JLU-P316Q toward CP congeners show significant difference, especially for active improvements of positional congeners such as 3-CP (1.1-fold) compared to 4-CP (3.0-fold), as well as 2,3-DCP (1.2-fold) compared to 2,5-DCP (3.4-fold). Structural analysis results indicate that the improvement in substrate promiscuity of the variant enzyme compared to the wild-type enzyme is possibly due to the increase of non-bonding interaction. The results suggest that exploiting enzyme–substrate promiscuity is promising, which would provide a starting point for designing and engineering novel biological catalysts for pollution removal.

In silico designed 2,4-DCP hydroxylase exhibits broader substrate promiscuity for chlorophenols than that of the wild-type enzyme.     

Blood pressure variability and outcome in acute severe stroke: A post hoc analysis of CHASE—A randomized controlled trial

The influence of blood pressure variability (BPV) on outcomes in patients with severe stroke is still largely unsettled. Using the data of CHASE trial, the authors calculated the BPV during the acute phase and subacute phase of severe stroke, respectively. The primary outcome was to investigate the relationship between BPV and 90‐day modified Rankin scale (mRS) ≥ 3. The BPV was assessed by eight measurements including standard deviation (SD), mean, maximum, minimum, coefficient of variation (CV), successive variation (SV), functional successive variation (FSV), and average real variability (ARV). Then, the SD of SBP was divided into quintiles and compared the quintile using logistic regression in three models. The acute phase included 442 patients, and the subacute phase included 390 patients. After adjustment, six measurements of BPV during the subacute phase rather than acute phase were strongly correlated with outcomes including minimum (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.69‐0.99, p = .037), SD (OR: 1.10, 95% CI: 1.03‐1.17, p = .007), CV (OR: 1.12, 95% CI: 1.03‐1.23, p = .012), ARV (OR: 1.13, 95% CI: 1.05‐1.20, p < .001), SV (OR: 1.09, 95% CI: 1.04‐1.15, p = .001), and FSV (OR: 1.12, 95% CI: 1.05‐1.19, p = .001). In the logistic regression, the highest fifth of SD of SBP predicted poor outcome in all three models. In conclusion, the increased BPV was strongly correlated with poor outcomes in the subacute phase of severe stroke, and the magnitude of association was progressively increased when the SD of BP was above 12.     

Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis

Platelet-derived growth factor (PDGF) is expressed in many different tumors, but its precise roles in tumorigenesis remain to be fully defined. Here, we report on a mouse model that demonstrates dose-dependent effects of PDGF-B on glial tumorigenesis. By removing inhibitory regulatory elements in the PDGFB mRNA, we are able to substantially elevate its expression in tumor cells using a retroviral delivery system. This elevation in PDGF-B production results in tumors with shortened latency, increased cellularity, regions of necrosis, and general high-grade character. In addition, elevated PDGF-B in these tumors also mediates vascular smooth muscle cell recruitment that supports tumor angiogenesis. PDGF receptor (PDGFR) signaling appears to be required for the maintenance of these high-grade characteristics, because treatment of high-grade tumors with a small molecule inhibitor of PDGFR results in reversion to a lower grade tumor histology. Our data show that PDGFR signaling quantitatively regulates tumor grade and is required to sustain high-grade oligodendrogliomas.     

复配式粗杂粮改善脂代谢紊乱作用的实验研究

目的探讨由米面和复配式粗杂粮等不同构成的饲料对脂代谢紊乱大鼠的作用。方法40只雄性SD大鼠随机分为阴性对照组、高脂模型对照组、米面组和粗杂粮组;以相应饲料连续喂养10周,测定各组大鼠体重、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)等指标,同时做肝脏组织病理检查。结果与高脂模型对照组比较,粗杂粮组大鼠的血清TG、TC水平显著下降,HDL-C水平显著升高,肝脏脂肪变性程度显著减轻。结论复配式粗杂粮对脂代谢紊乱大鼠脂代谢具有较好的改善作用。其特有的化学组分及生物学特性是取得较好效果的重要原因。     

Serous microcystic adenoma of the pancreatic head: Report of two cases and review of the literature

Serous microcystic adenomas (SMAs), also known as glycogen-rich cystadenomas, are uncommon exocrine tumors mainly involved in the body and tail of the pancreas. In this study, we report two SMA cases of the pancreatic head. In case 1, a 47-year-old woman was referred to our hospital for abdominal bloating and back pain; in case 2, a pancreatic space-occupying lesion was incidentally discovered in an asymptomatic 71-year-old female during an ultrasound. In both cases, a computer tomography scan showed well-demarcated and multilocular cysts in the head of the pancreas, and a central scar and calcifications were noted in case 1. During the exploratory laparotomies, the multiple cystic masses were found in the pancreatic head. A segmental resection of the pancreas and pancreatic jejunal anastomosis were performed. Histologically, the tumors were composed of tiny cysts that were filled with clear fluid and lined by a single layer of cuboidal cells with round, centrally located nuclei and clear cytoplasm, without cellular atypia. Immunohistochemical studies showed that the neoplastic cells were positive for cytokeratin 7 and vimentin but negative for synaptophysin and cytokeratin 20. A postoperative follow-up indicated no recurrence in the patients. We reviewed the literature regarding the etiology, clinical presentation, imaging characteristics, features and management of this lesion.     

Castleman病的CT表现

目的：提高对巨大淋巴结增生(Castleman病)CT表现的认识。方法：分析3例经手术病理或穿刺活检证实的巨大淋巴结增生患者的CT表现．总结其特征。结果：3例中2例病灶位于肠系膜，1例位于纵隔。动态增强CT扫描．所有的病灶在动脉期明显强化．在延迟期均表现为持续强化。结论：纵隔或肠系膜富血供的病变．在动脉期明显强化．延迟期持续强化．提示Castleman病的诊断。