Classification of cancer cell death with spectral dimensionality reduction and generalized eigenvalues

Objective

Accurate cell death discrimination is a time consuming and expensive process that can only be performed in biological laboratories. Nevertheless, it is very useful and arises in many biological and medical applications.

Methods and material

Raman spectra are collected for 84 samples of A549 cell line (human lung cancer epithelia cells) that has been exposed to toxins to simulate the necrotic and apoptotic death. The proposed data mining approach for the multiclass cell death discrimination problem uses a multiclass regularized generalized eigenvalue algorithm for classification (multiReGEC), together with a dimensionality reduction algorithm based on spectral clustering.

Results

The proposed algorithmic scheme can classify A549 lung cancer cells from three different classes (apoptotic death, necrotic death and control cells) with 97.78% ± 0.047 accuracy versus 92.22 ± 0.095 without the proposed feature selection preprocessing. The spectrum areas depicted by the algorithm corresponds to the 〉C O bond from the lipids and the lipid bilayer. This chemical structure undergoes different change of state based on cell death type. Further evidence of the validity of the technique is obtained through the successful classification of 7 cell spectra that undergo hyperthermic treatment.

Conclusions

In this study we propose a fast and automated way of processing Raman spectra for cell death discrimination, using a feature selection algorithm that not only enhances the classification accuracy, but also gives more insight in the undergoing cell death process.     

2型糖尿病患者血清抵抗素的检测及其与胰岛素抵抗的关系

目的 探讨检测血清抵抗素水平用于2型糖尿病诊断的意义,并分析其与胰岛素抵抗的关系. 方法 随机收集2型糖尿病患者117例、健康对照组109例,测定其空腹血糖、空腹胰岛素和抵抗素水平.比较上述指标在糖尿病患者和健康对照人群之间的差异.分析抵抗素用于糖尿病诊断的灵敏度、特异度、正确率和ROC曲线下面积.应用Pearson直线相关分析计算抵抗素与胰岛素抵抗指数的相关性. 结果 2型糖尿病患者的血清抵抗素、空腹血糖、空腹胰岛素及胰岛素抵抗指数均显著高于健康对照组(P<0.01).抵抗素用于糖尿病诊断的灵敏度为70.09%、特异度为64.22%、正确率为67.30%、ROC曲线下面积为0.695,诊断试验的准确度为中等.糖尿病患者的血清抵抗素水平与其胰岛素抵抗指数呈显著正相关(r=0.803,P<0.01). 结论 2型糖尿病的发生可能与抵抗素水平增高有关.检测血清抵抗素可用于糖尿病的辅助诊断,并可作为评价胰岛素抵抗程度的一种新的敏感指标.     

Stanford A型主动脉夹层患者双侧肾动脉受累影像解剖分型及其术后急性肾功能损伤的比较

目的:观察Stanford A型主动脉夹层患者双侧肾动脉受累的CT血管成像(CTA)影像解剖学分型,并探讨不同分型患者术后急性肾功能损伤(AKI)的差异。方法:回顾性研究。纳入2010年1月—2017年12月中国医学科学院阜外医院外科1 331例Stanford A型主动脉夹层患者影像及临床资料,其中男1 008例、女...     

高血压病和2型糖尿病患者血清损伤ECV-304细胞的比较研究

目的:以高血压病和2型糖尿病为例进行血瘀证血管内皮细胞损伤模型的比较研究,为中医学"异病同证"理论提供实验依据。方法:取对数生长期ECV-304细胞,分组如下:空白对照组(无血清的DMEM组)、糖尿病血瘀证组(糖尿病血瘀证患者血清)和高血压病血瘀证组(高血压病血瘀证患者血清)。采用噻唑蓝比色法(MTT法)观察细胞活性;在倒置相差显微镜、扫描电镜和透射电镜下观察细胞形态的变化;应用放免法测定内皮素(ET)含量;硝酸还原酶法测定一氧化氮(NO)含量;利用双抗夹心酶联免疫法(ELISA)检测各组细胞培养上清液中内皮细胞蛋白C受体(EPCR)、血管内假性血友病因子(vWF)和血栓调节蛋白(sTM)的含量;应用激光扫描共聚焦显微镜,采用Fluo-3/AM作为荧光指示剂观察细胞内游离钙([Ca2+]i)浓度的变化;并采用荧光探针标记的鬼笔环肽染色法观察细胞肌动蛋白微丝分布的差异。结果:(1)MTT结果显示,10%血清作用下,高血压病血瘀证组的细胞活力低于对照组(P0.05),糖尿病血瘀证组的细胞活力也低于对照组(P0.05),但高血压病血瘀证组的细胞活力与糖尿病血瘀证组差异无显著(P0.05);(2)高血压病血瘀证组的ET水平高于对照组(P0.05),糖尿病血瘀证组也高于对照组(P0.05),且高血压病血瘀证组的ET水平低于糖尿病血瘀证组(P0.05);高血压病血瘀证组的NO水平低于对照组(P0.05),糖尿病血瘀证组也低于对照组(P0.05),且高血压病血瘀证组的NO水平高于糖尿病血瘀证组(P0.05);(3)高血压病血瘀证组的EPCR、vWF和sTM含量高于对照组(P0.05),糖尿病血瘀证组也高于对照组(P0.05),且高血压病血瘀证组的EPCR水平低于糖尿病血瘀证组(P0.05);而高血压病血瘀证组的vWF和sTM含量与糖尿病血瘀证组之间差异无显著(P0.05);(4)高血压病血瘀证组[Ca2+]i高于对照组(P0.05),糖尿病血瘀证组[Ca2+]i高于对照组(P0.05),高血压病血瘀证组胞浆内荧光分布不均匀,[Ca2+]i高于糖尿病血瘀证组(P0.05);(5)高血压病血瘀证组可见细胞骨架微丝减少但排列较为规则,糖尿病血瘀证组的微丝断裂且排列紊乱,二者微丝分布差异显著。结论:高血压病患者血清和糖尿病患者血清对ECV-304细胞骨架、[Ca2+]i及ET、NO和EPCR表达的影响不同,但均能造成ECV-304细胞损伤,这可能是中医学"异病同证"的病理学基础。     

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1''kg/m²], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4''mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.     

不同治疗方式对新发2型糖尿病患者胰岛β细胞功能及胰岛素抵抗的影响

目的 比较采用胰岛素治疗(INS)与口服降糖药物治疗(OHA)等不同治疗方式对新发2型糖尿病(T2DM)患者胰岛β细胞功能及胰岛素抵抗的影响,推断新发T2DM的最佳治疗方案.方法 将62例新发T2DM患者随机分为胰岛素治疗组(INS组)和口服降糖药物组(OHA组).OHA组首选磺脲类或二甲双胍,或二者合用,疗效欠佳时增加噻唑烷二酮类,一般为2药或3药合用.两组治疗期均为3个月.每组根据血糖调整剂量,目标为空腹血糖(FBG)＜6.0 mmol/L,餐后2h血糖(2hPG)＜8.0mmol/L.观察两组治疗前后FBG、2h PG、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、空腹及餐后2hC肽(FCP、2hCP)水平的变化;用稳态模型(Homa)计算胰岛β细胞功能指数(Homaβ=20×FINS/(FBG-3.5)和胰岛素抵抗指数[HomaIR=(FBG×FINS)/22.5].用治疗后CP、Homaβ、HomaIR等相关指标进行组间比较,以评价胰岛β细胞功能及外周胰岛素抵抗的变化.结果 :(1)治疗后,两组患者FBG、2hPG、HbA1C水平较治疗前均有明显下降(P＜0.01),而在两组间比较差异无统计学意义;(2)治疗后,INS组患者FINS、FCP、2hCP、Homaβ较治疗前升高(P＜0.05),OHA组则无明显变化(P＞0.05),两组间比较差异有统计学意义(P＜0.05);(3)治疗后,INS组患者HomaIR较治疗前有明显下降(P＜0.05),OHA组仅略有下降,两组间比较差异有统计学意义(P＜0.05).结论 早期应用胰岛素治疗可以改善新发T2DM患者胰岛β细胞分泌功能及外周胰岛素抵抗.与OHA相比,INS能更好地保护患者的胰岛B细胞功能.     

Improvement in medication adherence and self-management of diabetes with a clinical pharmacy program: a randomized controlled trial in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital

OBJECTIVE:

To evaluate the impact of a clinical pharmacy program on health outcomes in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital in Brazil.

METHOD:

A randomized controlled trial with a 6-month follow-up period was performed in 70 adults, aged 45 years or older, with type 2 diabetes who were taking insulin and who had an HbA1c level ≥8%. Patients in the control group (CG) (n = 36) received standard care, patients in the intervention group (IG) (n = 34) received an individualized pharmacotherapeutic care plan and diabetes education. The primary outcome measure was change in HbA1c. Secondary outcomes included diabetes and medication knowledge, adherence to medication, insulin injection and home blood glucose monitoring techniques and diabetes-related quality of life. Outcomes were evaluated at baseline and 6 months using questionnaires.

RESULTS:

Diabetes knowledge, medication knowledge, adherence to medication and correct insulin injection and home blood glucose monitoring techniques significantly improved in the intervention group but remained unchanged in the control group. At the end of the study, mean HbA1c values in the control group remained unchanged but were significantly reduced in the intervention group. Diabetes-related quality of life significantly improved in the intervention group but worsened significantly in the control group.

CONCLUSION:

The program improved health outcomes and resulted in better glycemic control in patients with type 2 diabetes undergoing insulin therapy.     

2型糖尿病血管病变时血浆ANP、BNP及CNP的变化及临床意义

目的：探讨血浆心钠素(ANP)、脑利钠肽(BNP)、C型利钠肽(CNP)在2型糖尿病血管病变时的变化及其临床意义。方法:应用酶联免疫吸附法(ELISA)测定正常对照组(9例)、2型糖尿病无血管病变组(34例)及2型糖尿病血管病变组(23例)血浆proANP、BNP fragment及NT-proCNP浓度，分析各组间血浆利钠肽水平的变化及相关因素。结果:2型糖尿病血管病变组血浆ANP、BNP明显高于另外2组（P<0.01），而血浆CNP明显降低（P<0.01），2型糖尿病血管病变组各亚组(微血管病变组、大血管病变组及微血管合并大血管病变组)间血浆利钠肽水平无明显差异（P>0.05）。2型糖尿病血管病变组血浆ANP与BNP间存在显著正相关（r=0.309, P<0.05），ANP与CNP（r=-0.374, P<0.05）以及BNP与CNP（r=-0.653, P<0.01）间存在显著负相关。结论:血浆ANP、BNP及CNP的联合检测可以作为简便、价廉、可靠的糖尿病血管病变的筛选指标。     

Weight reduction improves markers of hepatic function and insulin resistance in type-2 diabetic patients with non-alcoholic fatty liver

Objective

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing dramatically affecting up to 30% of the population worldwide. At present, treatment options are limited and pharmacological management of NAFLD has had disappointing results. Some of the best available evidence to improve NAFLD concerns lifestyle modification.

Objective

To detect the degree of weight reduction needed to improve the markers of hepatic function and insulin resistance in type-2 diabetics with NAFLD.

Methods

One hundred type-2 diabetic male patients with NAFLD were included into this study and divided into two equal groups. Group (A) received aerobic exercise training in addition to diet regimen. Group (B) received no treatment intervention.

Results

There was a 26.99%, 40.8%, 33.81%, 32.73%, 37.8% and 15 % reduction in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT) and Homeostasis Model Assessment-Insulin Resistance-index (HOMA-IR) and BMI respectively in group (A) at the end of the study. While there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.

Conclusion

About 15 % reduction in BMI is effective to improve the liver condition and insulin resistance in type-2 diabetics with NAFLD.     

2型糖尿病患者CD14CD16单核细胞的水平及其对LPS和IL-15刺激的反应

目的: 研究2型糖尿病(T2DM)患者外周血CD14⁺CD16⁺单核细胞的比例及脂多糖(LPS)联合白细胞介素 15(IL-15)对其的影响,以了解炎症性免疫反应在T2DM中的可能作用机制。方法: 对28例T2DM患者和20例健康志愿者外周血用流式细胞术检测CD14⁺CD16⁺单核细胞的比例,并分离其外周血单个核细胞(PBMC),用LPS和IL-15干预4 h,收集PBMC和培养上清。分别采用Western blotting检测PBMC内STAT5和p-STAT5蛋白表达。免疫荧光检测p-STAT5蛋白表达,ELISA法检测外周血25-羟维生素D₃ 和IL-6浓度,免疫比浊法检测其外周血C-反应蛋白(CRP)水平, ELISA法检测LPS和IL-15干预后细胞培养上清IL-6和单核细胞趋化蛋白-1(MCP-1)的浓度。结果: T2DM组外周血CD14⁺CD16⁺单核细胞数量明显高于正常对照组(P<0.01),并与血清CRP和IL-6水平呈正相关(r=0.394,P<0.05和r=0.741,P<0.01),与25(OH)D₃浓度呈负相关(r=0.409,P<0.01),且25(OH)D₃水平与CRP和IL-6水平均呈负相关(r=-0.479和r=-0.774,均P<0.01),LPS联合IL-15刺激后PBMC的p-STAT5蛋白表达水平和PBMC培养上清IL-6、MCP-1浓度明显高于正常对照组(P<0.01),且T2DM患者p-STAT5的表达存在激活现象。结论: T2DM患者体内存在单核细胞功能紊乱,这种功能紊乱可能与活性维生素D₃不足有关,二者可能参与了T2DM患者体内免疫炎症反应并与微炎症互为因果,从而导致了T2DM及其并发症的发生发展;其作用机制可能与STAT5信号通路的激活有关。