Born approximation model for light scattering by red blood cells

The primary role of a red blood cell (RBC) is delivering oxygen throughout our body. Abnormalities of this basic function lead to anemia and are caused by numerous diseases such as malaria and sickle cell anemia. As prompt and inexpensive tests for blood screening are in demand, we have developed a faster and reliable way to measure morphological parameters associated with the structure of red blood cells and the size distribution of the cells in a whole blood smear. Modeling the RBC shape under Born approximation, we are able to determine parameters of clinical relevance, such as the diameter, thickness and dimple size. From a measured quantitative phase image of a blood smear, we can determine the average and standard deviation of the red blood cell volume simultaneously, i.e., without analyzing each cell individually. This approach may open the door for a new generation of label-free, high-throughput blood testing.     

组织工程皮肤构建中胎儿皮肤标本玻璃化冻存的实验

目的：建立一种用于细胞培养的皮肤标本新的保存方法。 方法：实验于2004-05-01／2-31在第四军医大学西京医院烧伤外科实验室进行。①分别取流产胎儿头部及躯干部全层皮片（家属知情同意），按照标本保存方法不同分为常规组（4℃保存2h）、冻存1组（-196℃液氮保存1周组）、冻存2组（-196℃液氮保存1个月组）和冻存3组（-196℃液氮保存6个月组）。采用抗冻液4℃下预处理20min后直接快速置于-196℃液氮中的玻璃化冻存方法进行冻存。②分别进行胎儿角质形成细胞、成纤维细胞和毛乳头细胞的原代培养，进行细胞形态学观察，并采用锥虫蓝染色法、四唑盐比色法和克隆形成实验观察培养的第2代角质形成细胞、成纤维细胞和毛乳头细胞的活力。 结果：①与常规组同种细胞相比，冻存1组、冻存2组和冻存3组的胎儿角质形成细胞、成纤维细胞和毛乳头细胞的形态学特点基本相同。②与常规组相比，冻存1组、冻存2组和冻存3组角质形成细胞、成纤维细胞和毛乳头细胞活细胞率、细胞存活率及克隆形成率差异均无显著性意义（P〉0．05）。 结论：利用液氮玻璃化保存用于细胞培养的皮肤标本不会影响细胞活力，是保持组织活性的一种有价值的组织标本保存方法，对组织工程皮肤的建立，乃至构建组织细胞库有着重要意义。     

高血压及冠心病与人类β3肾上腺素能受体多态性的关系

目的探讨β3肾上腺素能受体基因单核苷酸多态性与高血压、冠心病的关系. 资料来源应用计算机检索Medline1989-01/2004-03与高血压、冠心病及β3肾上腺素能受体基因单核苷酸多态性相关的文章,检索词"β3adrenergic receptor,polymorphism,hypertension,coronary heart disease",并限定语言种类为英文.同时计算机检索中国期刊全文数据库1994/01-2004/03与高血压、冠心病及β3肾上腺素能受体基因单核苷酸多态性相关的文章,限定文章语言种类为中文,检索词"肾上腺素能受体,多态性,高血压,冠心病". 资料选择对资料进行初审,选择包括和处理组和对照组的文献,筛除明显不符合研究目的文献,对剩余的文献开始查找全文.纳入标准为①随机对照研究.②实验或临床研究包含平行对照组.排除重复性研究和综述类文章. 资料提炼共收集到27篇关于β3肾上腺素能受体多态性与高血压、冠心病的文章,17个实验研究符合纳入标准.排除的10篇为重复研究. 资料综合①β3的多态性与高血压相关,也与一些其他高血压发展的独立危险因子有关,如高血脂、肥胖、尿酸、瘦素浓度.因此,关于Arg64与高血压冠心病的相关性,还是不能区分是直接起于Arg64,还是继发于代谢相关的危险因子.②冠心病的发生是多因素、多基因作用的结果.不同的生活方式与环境因素都可能对β3受体基因Trp64Arg突变的作用产生增强或削弱的作用,因而不同地区的研究表现出不同的结果,也即是基因Trp64Arg突变对冠心病发生的影响可能存在人种与地区的差别.而作为冠心病危险因素之一的体质量指数与Trp64Arg基因多态性也存在相关,与脂代谢紊乱、胰岛素抵抗,以及瘦素水平增高有着密切的关系.所以,β3受体基因Trp64Arg突变可能在冠心病发病中有一定作用,但不是决定因素,也不是冠心病的主要预测因子.其对冠心病发生的影响可能是通过影响冠心病发生的潜在危险因素如体质量指数发挥作用. 结论冠心病和高血压是多种危险因素、多基因遗传的复杂病.高血压、冠心病与β3受体基因多态性的研究中关系怎样还是不明确.虽然β3受体基因Trp64Arg突变在高血压病和冠心病的遗传因素中不起主要作用,现在看来β3的多态性不太可能是疾病(如高血压和冠心病)的诱发基因,但他可能促使代谢疾病的早期发生,也许是一个重要的疾病危险因子,影响、调节疾病的进程.     

Subcellular organization of camkii in rat hippocampal pyramidal neurons

Calcium/calmodulin‐dependent protein kinase II (CaMKII) plays a key role in N‐methyl‐D‐aspartate (NMDA) receptor‐dependent long‐term synaptic plasticity; its location is critical for signal transduction, and may provide clues that further elucidate its function. We therefore examined the subcellular localization of CaMKII in CA1 stratum radiatum of adult rat hippocampus, by using immuno‐electron microscopy after chemical fixation. When tissue was fixed quickly, the concentration of CaMKIIα (assessed by pre‐embedding immunogold) was significantly higher in dendritic shafts than in spine heads. However, when tissue was fixed 5 minutes after perfusion with normal saline, the density of labeling decreased in dendritic shaft while increasing in spine heads, implying rapid translocation into the spine during brief perimortem stress. Likewise, in quickly fixed tissue, CaMKII within spine heads was found at comparable concentrations in the “proximal” half (adjacent to the spine neck) and the “distal” half (containing the postsynaptic density [PSD]), whereas after delayed fixation, label density increased in the distal side of the spine head, suggesting that CaMKII within the spine head moves toward the PSD during this interval. To estimate its distribution at the synapse in vivo, we performed postembedding immunogold staining for CaMKII in quick‐fixed tissue, and found that the enzyme did not concentrate primarily within the central matrix of the PSD. Instead, labeling density peaked ～40 nm inside the postsynaptic membrane, at the cytoplasmic fringe of the PSD. Labeling within 25 nm of the postsynaptic membrane concentrated at the lateral edge of the synapse. This lateral “PSD core” pool of CaMKII may play a special role in synaptic plasticity. J. Comp. Neurol. 521:3570‐3583, 2013. © 2013 Wiley Periodicals, Inc.     

Selective targeting of checkpoint kinase 1 in tumor cells with a novel potent oncolytic adenovirus.

DNA-damage checkpoints are activated to arrest cells and promote survival upon genotoxic challenge. Efforts have been taken to target checkpoint kinase 1 (chk1; approved gene symbol CHEK1), a crucial checkpoint modulator, for therapeutic intervention. However, improvement of the potency and specificity of such therapeutics remains a major challenge. This prompted us to develop a novel chk1-targeting strategy by constructing a potent oncolytic adenovirus (M2). M2 was generated by combining two artificial features into a wild-type adenovirus type 5 genome. First, M2 was engineered with a 27-bp deletion in the E1A region to confer tumor-selective replication. Second, an antisense chk1 cDNA was substituted for viral E3 6.7K and gp19K genes. In this design, M2 exploited the adenovirus E3 promoters to express antisense chk1 cDNA in a viral replication-dependent fashion and preferentially silenced the chk1 gene in tumor cells. By virtue of combining oncolysis with chk1 targeting, M2 exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M2, plus a low dose of cisplatin, cured 80% of orthotopic hepatic carcinoma mouse models that were otherwise resistant to cisplatin. These findings have directed us toward the development of novel oncolytic adenoviruses that will be potentially applicable to a wide range of molecular-based therapeutics.     

Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype

Background and AimsTransplantation of mesenchymal stem cells (MSCs) derived from bone marrow (BM) is an alternative treatment of acute liver failure (ALF) mainly because of the resulting anti-inflammatory activity. It is not known how MSCs regulate local immune responses and liver regeneration. This study explored the effects of MSCs on hepatic macrophages and the Wnt signaling pathway in ALF.MethodsMSCs were isolated from BM aspirates of C57BL/6J mice, and transplanted in mice with ALF induced by D-galactosamine (D-Gal). The proliferation of hepatocytes was assayed by immunohistochemical (IHC) staining of Ki-67 and proliferating cell nuclear antigen (PCNA). The levels of key proteins in the Wnt signaling pathway were assayed by western blotting and cytokines were determined enzyme-linked immunosorbent assays (ELISAs). A macrophage polarization assay characterized the M1/M2 ratio. The potential role of interleukin-4 (IL-4) in the biological activity of MSCs was determined by silencing of IL-4.ResultsTransplantation of allogeneic MSCs significantly attenuated D-Gal-induced hepatic inflammation and promoted liver regeneration. MSC transplantation significantly promoted a phenotypic switch from proinflamatory M1 macrophages to anti-inflammatory M2 macrophages, leading to significant Wnt-3a induction and activation of the Wnt signaling pathway in mice with D-Gal-induced ALF. Of the paracrine factors secreted by MSCs (G-CSF, IL-6, IL-1 beta, IL-4, and IL-17A), IL-4 was specifically induced following transplantation in the ALF model mice. The silencing of IL-4 significantly abrogated the phenotypic switch to M2 macrophages and the protective effects of MSCs in both the ALF model mice and a co-culture model in an IL-4 dependent manner.ConclusionsIn vivo and in vitro studies showed that MSCs ameliorated ALF through an IL-4-dependent macrophage switch toward the M2 anti-inflammatory phenotype. The findings may have clinical implications in that overexpression of IL-4 may enhance the therapeutic effects of allogeneic MSC transplantation in the treatment of ALF.     

抚触对促进早期新生儿生长发育的作用

[目的]探讨抚触对早期新生儿生长发育的作用。[方法]对出生后1d的新生儿每日进行抚触,以同期出生的新生儿为对照,观察抚触后早期新生儿的进奶量、胎便排完时间及生理性体重下降率。[结果]抚触能增加早期新生几的进奶量,缩短胎便排完的时间,减少新生儿生理性体重下降。[结论]抚触能促进早期新生儿的生长发育。     

Application value of continuous seromuscular layer sutures in the reinforcement of esophagojejunostomy in total gastrectomy for gastric cancer: a retrospective comparative cohort study

BackgroundThe development process of gastrointestinal anastomosis is from complex to simple, from two layers to one layer, from extramucosal anastomosis to seromuscular anastomosis. With the rapid development of anastomosis instruments, the anastomosis process becomes more and more convenient. However, relevant studies have shown that related complications such as anastomotic leakage still occur. This study sought to investigate the feasibility and safety of seromuscular layer sutures in the reinforcement of esophagojejunostomy after open radical total gastrectomy.MethodsThis study retrospectively analyzed patients who underwent Roux-en-Y esophagojejunostomy after open radical total gastrectomy at The Third Department of Surgery, The Fourth Hospital of Hebei Medical University from April 2019 to May 2020. The inclusion criteria of patients were between 18 and 80 years old; pathology confirmed gastric adenocarcinoma; preoperative imaging showed no distant metastasis and did not receive neoadjuvant therapy; no complex infectious diseases; no blood transfusion was performed before operation. A total of 192 patients were included according to the inclusion criteria. They were divided into the following 2 groups based on whether seromuscular layer suturing of the anastomosis was performed: (I) group A (the simple anastomosis group, n=76); (II) and group B (the seromuscular layer suture group, n=116). The baseline data, surgical data and postoperative complications were compared between the two groups.ResultsAll patients underwent esophagojejunostomy Roux-en-Y anastomosis after open radical total gastrectomy, and no perioperative deaths occurred. There was no significant difference in baseline data between the two groups. Group B had an earlier time to liquid diet than group A (4.23±0.76 vs. 4.57±0.58 days, P<0.001). The incidence of postoperative anastomotic leakage in group B (1.72%) was lower than that in group A (9.21%), and the difference was statistically significant (P=0.03). The incidence of pleural effusion was lower in group B (15.52%) than group A (32.89%), and the difference was statistically significant (P=0.005).ConclusionsCompared to the simple anastomosis, seromuscular layer sutures after esophagojejunostomy may decrease the rates of postoperative anastomotic leakage and pleural effusion. This suture method is feasible and may provide a new option to increase surgical safety.