输尿管软镜结合输尿管硬镜治疗复杂上尿路结石的效果评价及对预后的影响

目的探讨输尿管软镜协同输尿管硬镜治疗复杂上尿路结石的临床效果。方法选择我院收治的复杂上尿路结石患者96例,按入院顺序分为对照组和观察组,每组48例。对照组采取输尿管硬镜钬激光碎石术治疗,观察组采取输尿管软镜协同输尿管硬镜钬激光碎石术治疗。比较两组患者1次性碎石成功率、结石彻底清除率、炎症反应情况以及生活质量、住院时间、术后并发症发生率、疾病复发率。结果观察组患者的1次性碎石成功率、结石彻底清除率均高于对照组,两组比较差异有统计学意义(均P<0.05)。术后3 d,观察组的肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、C-反应蛋白(CRP)水平均较对照组降低,差异有统计学意义(均P<0.05)。术后1周,两组患者的生活质量比较,观察组的生活质量量表(SF-36)评分明显高于对照组,住院时间短于对照组,两组比较差异有统计学意义(均P<0.05)。两组患者的并发症发生率、疾病复发率比较,观察组均明显低于对照组,差异有统计学意义(均P<0.05)。结论输尿管软镜联合输尿管硬镜治疗复杂上尿路结石的效果满意,且创伤小,结石清除率高,不良反应低,具有一定临床应用价值。     

含半胱氨酸的天冬氨酸蛋白水解酶(caspase-1)对猪伪狂犬病毒复制的影响

猪伪狂犬病是伪狂犬病毒(Pseudorabies virus,PRV)感染引起的一种烈性接触性传染病,其感染宿主会触发机体先天免疫应答,引起I型干扰素(Type I interferon,IFN-1)和炎性细胞因子等细胞因子的产生,为研究可诱导产生炎性细胞因子的含半胱氨酸的天冬氨酸蛋白水解酶(Cysteinyl aspartate specific proteinase 1,caspase-1)的基因敲除对PRV复制的影响,本试验利用近年来发展迅速的一项规律性短重复回文序列簇/Cas9核酸酶(Clustered regulatory interspaced short palindromic repeat/CRISPR associated system 9,CRISPR/Cas9)基因定点修饰技术构建猪肾上皮细胞(Porcine kidney epithelial cells,PK15)caspase-1基因稳定敲除细胞系,并通过T7核酸酶检测敲除效率;细胞毒性(Cell counting kit-8,CCK-8)试剂盒检测PK15敲除caspase-1增殖影响;采用流式细胞术检测PRV-GFP感染PK15以及PK15-caspase-1^-/-的增殖差异;实时荧光定量PCR(Real-time quantitative PCR,RT-PCR)检测PRV-gB、TK及白细胞介素1β(Interleukin-1β,IL-1β)、IFN-β、干扰素刺激基因(Interferon-stimulated genes 20,ISG20)mRNA的表达;Western Blot检测PRV-gB蛋白表达;滴度测定检测子代病毒滴度。结果表明,2对特异性单链引导RNA(Single guide RNA,sgRNA)均能对caspase-1进行基因编辑,但经T7核酸酶酶切进行基因编辑效率分析结果表明sgRNA2的基因编辑效率较高;CCK-8试剂盒检测细胞活力结果表明caspase-1基因敲除对PK15以及PK15-caspase-1^-/-细胞活力无影响(P>0.05);流式细胞仪检测结果表明PRV-GFP在PK15-caspase-1^-/-中的增殖显著低于PK15细胞(P<0.05);定量RT-PCR结果表明PRV-gB、TK基因在PK15-caspase-1^-/-的mRNA表达显著低于PK15细胞(gB:P<0.05,TK:P<0.05),而IFN-β、ISG20基因在PK15-caspase-1^-/-的mRNA表达显著高于PK15细胞(gB:P<0.05,TK:P<0.05);Western Blot结果表明,PRV的gB蛋白在PK15-caspase-1^-/-的表达显著低于PK15细胞(P<0.05);滴度测定结果表明,敲除caspase-1能够抑制PRV子代病毒的增殖。以上结果均表明caspase-1基因敲除可抑制PRV在PK15细胞中复制。     

泌尿系统结石合并感染患者尿路病原菌分布及危险因素分析

目的分析泌尿系统结石合并感染患者尿路病原菌分布及其危险因素,为后续研究提供参考。方法收集2016年1月至2019年1月我院诊治的430例泌尿系统结石患者为研究对象,根据患者是否发生感染分为感染组(n=34)和非感染组(n=396)。分析两组患者的临床特征和感染组患者病原菌分布情况,同时对影响患者感染的高危因素进行Logistic回归分析。结果感染组患者共计检出84株病原菌,其中革兰阳性球菌20株(23.81%),革兰阴性杆菌60株(71.43%),其他4株(4.76%)。两组患者白细胞水平、尿路梗阻情况、血肌酐水平、尿pH7.0比例、血尿素氮水平、合并肾积水情况、结石位置、结石直径、抗菌药物使用种类差异均有统计学意义(均P0.05)。合并肾积水、尿路梗阻、白细胞计数(≤10×10~9个/L)、尿pH(7.0)、血尿素氮(≥7.15 mmol/L)、结石位置(上尿路)、抗菌药物使用种类(≥3种)均为泌尿系统结石合并尿路感染的高危因素,而血肌酐水平,结石直径与泌尿系统结石合并尿路感染无明显相关性。结论泌尿系统结石患者易并发尿路感染,其病原菌以革兰阴性杆菌为主。导致尿路感染的因素较多,临床上应提前制定预防措施,降低结石患者尿路感染发生率。     

Curcumin alleviates acute kidney injury in a dry‐heat environment by reducing oxidative stress and inflammation in a rat model

Curcumin exhibits anti‐inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry‐heat conditions. We divided Sprague‐Dawley rats into four groups: dry‐heat 0‐ (normal temperature control group), 50‐, 100‐, and 150‐minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high‐dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule‐1, and neutrophil gelatinase‐associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry‐heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150‐minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100‐ and 200‐mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX‐2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti‐inflammatory effects in a dry‐heat environment rat model.     

Generalized lattice graphs for 2D-visualization of biological information

Several graph representations have been introduced for different data in theoretical biology. For instance, complex networks based on Graph theory are used to represent the structure and/or dynamics of different large biological systems such as protein-protein interaction networks. In addition, Randic, Liao, Nandy, Basak, and many others developed some special types of graph-based representations. This special type of graph includes geometrical constrains to node positioning in space and adopts final geometrical shapes that resemble lattice-like patterns. Lattice networks have been used to visually depict DNA and protein sequences but they are very flexible. However, despite the proved efficacy of new lattice-like graph/networks to represent diverse systems, most works focus on only one specific type of biological data. This work proposes a generalized type of lattice and illustrates how to use it in order to represent and compare biological data from different sources. We exemplify the following cases: protein sequence; mass spectra (MS) of protein peptide mass fingerprints (PMF); molecular dynamic trajectory (MDTs) from structural studies; mRNA microarray data; single nucleotide polymorphisms (SNPs); 1D or 2D-Electrophoresis study of protein polymorphisms and protein-research patent and/or copyright information. We used data available from public sources for some examples but for other, we used experimental results reported herein for the first time. This work may break new ground for the application of Graph theory in theoretical biology and other areas of biomedical sciences.     

Stability and structural constraints of random brain networks with excitatory and inhibitory neural populations

The stability of brain networks with randomly connected excitatory and inhibitory neural populations is investigated using a simplified physiological model of brain electrical activity. Neural populations are randomly assigned to be excitatory or inhibitory and the stability of a brain network is determined by the spectrum of the network’s matrix of connection strengths. The probability that a network is stable is determined from its spectral density which is numerically determined and is approximated by a spectral distribution recently derived by Rajan and Abbott. The probability that a brain network is stable is maximum when the total connection strength into a population is approximately zero and is shown to depend on the arrangement of the excitatory and inhibitory connections and the parameters of the network. The maximum excitatory and inhibitory input into a structure allowed by stability occurs when the net input equals zero and, in contrast to networks with randomly distributed excitatory and inhibitory connections, substantially increases as the number of connections increases. Networks with the largest excitatory and inhibitory input allowed by stability have multiple marginally stable modes, are highly responsive and adaptable to external stimuli, have the same total input into each structure with minimal variance in the excitatory and inhibitory connection strengths, and have a wide range of flexible, adaptable, and complex behavior.     

Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies

Frontal cortex samples from frozen human brains were used to assess tissue respiration; content of mitochondria; mitochondrial oxygen uptake; activity of respiratory complexes and of mitochondrial nitric oxide synthase (mtNOS); content of cytochromes a, b, and c; oxidative damage (protein carbonyls and TBARS); and expression of Mn-SOD in patients with Parkinson disease (PD) and with dementia with Lewy bodies (DLB) in comparison with those of normal healthy controls. Brain cortex and mitochondrial O₂ uptake and complex I activity were significantly lower in PD and DLB, whereas mtNOS activity, cytochrome content, expression of Mn-SOD, mitochondrial mass, and oxidative damage were significantly higher in the frontal cortex in PD and DLB. The decreases in tissue and mitochondrial O₂ uptake and in complex I activity are considered the consequences of mitochondrial oxidative damage. The increases in mtNOS activity and in mitochondrial mass are interpreted as an adaptive response of the frontal cortex that involves increased NO signaling for mitochondrial biogenesis. The adaptive response would partially compensate for mitochondrial dysfunction in these neurodegenerative diseases and would afford a human evolutionary response to shortage of ATP in the frontal cortex.     

A therapeutic antibody and its antigen form different complexes in serum than in phosphate-buffered saline: A study by analytical ultracentrifugation

During the development of protein therapeutics, characterization of the active pharmaceutical ingredient is performed extensively to ensure the stability, safety, and efficacy of the drug. Little is known, however, about the characteristics of protein drugs circulating in the blood. The recent availability of a fluorescence detection system (FDS) in analytical ultracentrifugation (AUC) instruments enables the characterization of fluorescently labeled proteins in biological fluids. AUC provides information about protein size, shape, self-association, and binding while avoiding many limitations associated with size exclusion chromatography. Furthermore, with the specificity and sensitivity of FDS, measurements can be performed at physiological concentrations directly in serum. In the current study, we used omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, to demonstrate the potential of using AUC-FDS for the study of a monoclonal antibody and its complexes directly in human serum. Omalizumab properties were essentially unaltered after labeling with the fluorescent dye Alexa Fluor 488. In addition, omalizumab and IgE formed different complexes in serum than in phosphate-buffered saline in terms of both size and affinity.