Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation

Three-dimensional (3D) culturing mimics the heterogeneous cellular conditions of the in vivo tumor microenvironment compared to 2D monolayer-cultured cells and 3D cultures of established cancer cell lines (sphere culture) or patient-derived cancer cells (organoid culture) are frequently used for cancer research or drug screening and evaluation. To establish more cost and time-efficient 3D culture methods for cancer cell lines, we supplemented sphere culture medium with polyvinyl alcohol (PVA) and found that 3D sphere cultures of breast and pancreatic cancer cell lines were significantly increased. Mechanistically, we found that PVA prevented cell death and promoted cellular proliferation while maintaining levels of stemness-related gene expression. Furthermore, we showed that polyvinyl formal resin (PVF) 3D scaffolds made by cross-linked PVA can function in serum-free, long-term 3D cultures to support maintenance of sphere- or tumor-like cell masses for diverse cancer cell types. Taken together, we demonstrate the effectiveness of PVA and PVF in human cancer cell line culture protocols.     

Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers

BACKGROUND: Left ventricular (LV) diastolic dysfunction has been observed in cigarette smokers with coronary artery disease. The aim of the study was to assess LV and right ventricular (RV) diastolic function in healthy, young, and slim smokers before and after smoking one cigarette. MATERIAL AND METHODS: The participants were 66 healthy volunteers (age < 40 years; body mass index < 25 kg/m(2)): 33 smokers (study group [HS]) and 33 nonsmokers (control group). Echocardiographic examination was done in the HS before smoking one cigarette (HS-1) and after smoking one cigarette (HS-2). To assess diastolic function of LV and RV mitral valve flow (MVF), pulmonary venous flow (PVF) and tricuspid valve flow (TVF) were evaluated. RESULTS: MVF early to late phase ratio (E/A) was significantly lower in HS-1 and HS-2 than in the control group. The PVF systolic to diastolic phase ratio (S/D) was significantly higher in HS-1 and HS-2 than in the control group. These changes suggest LV diastolic function impairment in the HS, but the MVF pattern remained within the normal range. PVF S/D showed systolic dominance (S/D > 1) typical for impaired LV relaxation and abnormal for this age group. TVF E/A was significantly lower in HS-2 than in HS-1 and control subjects and suggests RV diastolic dysfunction. CONCLUSIONS: The following conclusion are made: (1) MVF and PVF demonstrate LV relaxation impairment in healthy smokers before and after smoking one cigarette; (2) the assessment of PVF is a good method reflecting LV diastolic function changes, even when MVF remains normal; and (3) TVF shows RV relaxation impairment after smoking one cigarette in healthy smokers.     

非风湿性房颤患者肺静脉血流超声特征及其与左心耳改变的关系

目的了解非风湿性房颤(NRH-AF)患者的肺静脉血流(PVF)超声特征及其与左心耳(LAA)改变间的关系.方法研究了20例正常人PVF超声特征和36例NRH-AF患者的PVF及LAA超声特点.结果 LAA血流频谱清晰型(峰速≥25 cm/s,占61.5%)和LAA血流频谱模糊型(峰速<25 cm/s,占38.5%)两组患者的PVF频谱均表现为收缩期血流(峰速血流及速度积分,Sp及Si)显著减小而舒张期PVF峰速血流(Dp)反而增大的正向两相型(P＜0.01),所有患者房缩期返转波消失或弱不可辨.与前组患者相比,后组患者的Sp及Si、左心耳面积变化率、左心耳排血峰速、充盈血流峰速均显著减小,左心耳最大直径增大,自发性回声造影(SEC)现象检出率显著增高(64.2% VS 13.5%,P＜0.01),且28.5%患者发现血栓,而两组间Dp、左房室内径、心功能及二尖瓣环下降幅度无显著性差异(P＞0.05).相关分析表明:患者PVF的Sp与左心耳面积变化率、左心耳排血峰速、充盈血流峰速及左心耳最大直径有良好的相关性(r为0.68;0.60;0.42;-0.52,P＜0.01).结论非风湿性房颤患者的PVF变化有其特点且与LAA功能改变间关系密切,理解PVF表现应考虑LAA的作用,超声观察PVF亦可能有助了解患者LAA的功能.     

龙岩市136名煤工尘肺患者肺通气功能测定结果分析

[目的]研究煤工尘肺患者肺通气功能的损害情况。[方法]对136名煤工尘肺患者(接触组)和83名对照人员(对照组)进行肺通气功能测定。[结果]①接触组肺通气功能异常检出率高于对照组(P<0.01)。②接触组肺通气功能指标低于对照组(P<0.05或P<0.01)。③接触组吸烟者肺通气功能指标低于不吸烟者(P<0.05或P<0.01)。④接触组随着年龄的增加,MMF和V25呈下降趋势(P<0.05);随着工龄的延长,MMF、V25、V50、V75、Vmax呈现下降趋势(P<0.05)。[结论]长期接触煤尘的煤工尘肺患者肺通气功能明显降低,吸烟与煤尘可能产生协同作用,工人的肺通气功能损伤有随工龄的延长和年龄的增加而加重的趋势。     

A measles outbreak in a middle school with high vaccination coverage and evidence of prior immunity among cases,Beijing, P.R. China

BackgroundAge-appropriate receipt of ≥2 measles-containing vaccine (MCV) doses has been considered evidence of immunity against measles. Transmission of measles is rarely reported among such persons.MethodsWe report a measles outbreak in a middle school in Beijing that has high coverage with≥2 documented MCV doses. History of previous measles and documentation of MCV receipt were collected for all individuals. Cases were identified by active surveillance and confirmed by laboratory tests. Measles immunoglobulin G (IgG) titers and clinical presentations were obtained for each case.ResultsOf 1331 individuals without a prior history of measles, 1172 (88.1% [95%CI:86.4–91.5%]) and 1078 (81.0% [95%CI:78.9–83.1%]) had age-appropriate receipt of ≥2 MCV doses by domestic and U.S. CDC/ACIP criteria, respectively. Thirteen measles cases occurred in the outbreak. The index case and 3 secondary cases were students. The 9 tertiary cases included 2 teachers and 7 students. All 11 student cases received ≥2 age-appropriate MCV doses by Chinese domestic criteria; 8 were age-appropriately vaccinated by U.S. CDC/ACIP criteria. Measles IgG was detected during the acute phase of measles for all but 2 cases -the first case and 1 tertiary case. Among students with age-appropriate receipt of ≥2 MCV doses, the length of time since the last MCV was significantly associated with risk of measles: for the 1172 students, the risk was 4.6 [OR5.6;95%CI:1.4–22.9] and 5.5 [OR6.5;95%CI:1.4–29.8] times higher when the last MCV dose was 5–9 years and ≥10 years prior, respectively, compared with <5 years prior; for the 1078 students, the risk was 4.1 [OR5.1;95%CI:1.3–20.7] times higher when the last MCV dose was 5–9 years prior compared with <5 years prior.ConclusionsThis is the first report from China showing measles transmission among persons with prior evidence of immunity. Secondary vaccine failure may have played an important role in measles transmission. Further laboratory surveillance is needed to assess the persistence of vaccine-induced immunity of domestically-produced MCV in China.     

Gliatrophic and gliatropic roles of PVF/PVR signaling during axon guidance

Evidence of molecular and functional homology between vertebrate and Drosophila glia is limited, restricting the power of Drosophila as a model system to unravel the molecular basis of glial function. Like in vertebrates, in the Drosophila central nervous system glial cells are produced in excess and surplus glia are eliminated by apoptosis adjusting final glial number to axons. The underlying molecular mechanisms are largely unknown, as the only gliatrophic pathway known to date in flies is the EGFR and its ligands. The PDGFR signaling pathway plays a major role in regulating oligodendrocyte migration and number in vertebrates. Here, we show that the Drosophila PDGFR/VEGFR homologue PVR is required in midline glia during axon guidance for glial survival and migration, ultimately enabling axonal enwrapment. The midline glia migrate aided by the VUM and the MP1 midline neurons--sources of PVF ligands--and concomitantly interactions with neurons maintain midline glia survival. Upon loss of function for PVF/PVR signaling midline glia apoptosis increases, and gain of function induces supernumerary midline glia. Midline glial cells are displaced towards ectopic sources of PVF ligands. PVR signaling promotes midline glia survival through AKT and ERK pathways. This work shows that the PVR/PDGFR pathway plays conserved gliatrophic and gliatropic roles in subsets of glial cells in flies and vertebrates.     

Flexible modeling of longitudinal highly skewed outcomes

The analysis of data from epidemiologic and environmental studies presents challenges such as skewness of distribution, rounding and multiple measurements over time. To model trends over time based on repeated measurements, we propose a general latent model suitable for highly skewed data. The model assumes that the observed outcome is determined by an unobservable outcome that follows a Weibull distribution. To accommodate correlations among repeated responses over time, we introduce a general random effect from the power variance function (PVF) family of distributions, including the gamma distribution often employed in the literature. The resulting marginal likelihood has a closed form without resorting to numerical or approximation methods. We study estimation and hypothesis testing under these models, with different choices of random effect distributions. Simulation studies are conducted to evaluate their performance. Finally, we apply the proposed method to exposure data collected from the Michigan polybrominated biphenyl (MIPBB) study. Copyright © 2009 John Wiley & Sons, Ltd.     

酚磺乙胺联合奥曲肽治疗肝硬化上消化道出血的临床研究

目的探究酚磺乙胺注射液联合醋酸奥曲肽注射液治疗肝硬化上消化道出血的临床疗效。方法选取2011年3月—2016年6月中国人民解放军白求恩国际和平医院二五六临床部消化内科收治的肝硬化上消化道出血患者64例作为研究对象,在随机分组的原则下将所有患者分为对照组和治疗组,每组各32例。对照组静脉滴注醋酸奥曲肽注射液,0.1 mg加入到0.9%氯化钠溶液250 m L中,滴注速度0.025 mg/h,1次/d。治疗组在对照组基础上静脉滴注酚磺乙胺注射液,0.5 g加入5%葡萄糖注射液250 m L中,2次/d。两组患者均连续治疗4 d。观察两组的临床疗效,比较两组的临床指标、肝纤维化指标和门静脉血流量(PVF)。结果治疗后,对照组和治疗组的总有效率分别为75.00%、96.88%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组止血时间、住院时间和输血量均明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组人Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、PVF均显著性降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论酚磺乙胺注射液联合醋酸奥曲肽注射液治疗肝硬化上消化道出血具有较好的临床疗效,可改善肝纤维化,缩短止血时间和住院时间,减少输血量,降低门静脉压力,安全性较好,具有一定的临床推广应用价值。     

多普勒超声对正常人二尖瓣口及肺静脉血流频谱的分析

目的利用多普勒超声观察正常人二尖瓣口及肺静脉血流频谱的变化,旨在探讨其影响因素及其间的相互关系.方法108例正常的健康人,平均年龄43 1±15.7岁.脉冲多普勒记录二尖瓣口血流频谱(MIF)及肺静脉血流频谱(PVF)参数.结果(1)MIF参数A、Ai、AF随年龄增长而升高,E、Ei、E/A随年龄增长而降低;PVF参数S、Si、S/D及SF随年龄增长而升高,D、Di随年龄的增长而降低.(2)在一定心率范围内,随着心率加快,MIF参数EI与PVF参数DI降低,SF增高.(3)MIF参数E、Ei、E/A、AF、APVF参数D、Di、S/D、SF、AR均有较好的相关性.结论正常人MIF和PVF的多普勒超声表现会受年龄、心率等些因素的影响,但其相互之间有着本质的联系.     

Improvement of morphological changes after 70% hepatectomy with portocaval shunt: preclinical study in porcine model

BACKGROUND: After extensive hepatectomy, excessive portal venous flow (PVF) and elevated portal venous pressure (PVP) may lead to postoperative liver damage. We have evaluated the use of portocaval shunt (PCS) to control PVF and PVP following partial hepatectomy (PH) to reduce the postoperative liver damage. METHOD: Twenty-four pigs were divided into two Groups: Group C (n = 10) underwent 70% PH alone and Group S (n = 14) underwent 70% PH with PCS. The changes in PVF, PVP, serum liver function tests, and histology were evaluated. RESULTS: PVP and PVF per unit of remnant liver weight and serum total bilirubin levels in Group S were significantly lower than those in Group C postoperatively (P < 0.05). Histology showed that there were significant differences in hepatocyte ballooning, necrosis, and neutrophil aggregation between the two groups (P < 0.05). In particular, hepatic necrosis was observed in zone 3 of Group C as centrilobular necrosis. These results suggest that hepatic and sinusoidal damage after 70% PH were more severe in Group C than in Group S, with the latter group maintaining an almost normal ultrastructural appearance. Hepatocyte apoptotic index differed significantly between the two groups (P < 0.0001). CONCLUSION: After 70% PH, extensive centrolobular necrosis and neutrophil aggregation were present and may have caused liver damage, manifested as hyperbilirubinemia and coagulopathy. The delayed liver regeneration with PCS may reduce the postoperative liver damages rather than the rapid liver hypertrophy. The diversion of PVF with PCS to maintain adequate PVP is a very effective procedure for avoiding the postoperative liver failure after extensive hepatectomy.