Non-invasive Parenchymal,Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive performance-competitive means for cortical and internal brain imaging, retaining a significant potential in many neurologic fields.     

Distinguishing enzyme structures from non-enzymes without alignments

The ability to predict protein function from structure is becoming increasingly important as the number of structures resolved is growing more rapidly than our capacity to study function. Current methods for predicting protein function are mostly reliant on identifying a similar protein of known function. For proteins that are highly dissimilar or are only similar to proteins also lacking functional annotations, these methods fail. Here, we show that protein function can be predicted as enzymatic or not without resorting to alignments. We describe 1178 high-resolution proteins in a structurally non-redundant subset of the Protein Data Bank using simple features such as secondary-structure content, amino acid propensities, surface properties and ligands. The subset is split into two functional groupings, enzymes and non-enzymes. We use the support vector machine-learning algorithm to develop models that are capable of assigning the protein class. Validation of the method shows that the function can be predicted to an accuracy of 77% using 52 features to describe each protein. An adaptive search of possible subsets of features produces a simplified model based on 36 features that predicts at an accuracy of 80%. We compare the method to sequence-based methods that also avoid calculating alignments and predict a recently released set of unrelated proteins. The most useful features for distinguishing enzymes from non-enzymes are secondary-structure content, amino acid frequencies, number of disulphide bonds and size of the largest cleft. This method is applicable to any structure as it does not require the identification of sequence or structural similarity to a protein of known function.     

Molecular basis for substrate recognition and septum cleavage by AtlA,the major N-acetylglucosaminidase of Enterococcus faecalis

The cleavage of septal peptidoglycan at the end of cell division facilitates the separation of the two daughter cells. The hydrolases involved in this process (called autolysins) are potentially lethal enzymes that can cause cell death; their activity, therefore, must be tightly controlled during cell growth. In Enterococcus faecalis, the N-acetylglucosaminidase AtlA plays a predominant role in cell separation. atlA mutants form long cell chains and are significantly less virulent in the zebrafish model of infection. The attenuated virulence of atlA mutants is underpinned by a limited dissemination of bacterial chains in the host organism and a more efficient uptake by phagocytes that clear the infection. AtlA has structural homologs in other important pathogens, such as Listeria monocytogenes and Salmonella typhimurium, and therefore represents an attractive model to design new inhibitors of bacterial pathogenesis. Here, we provide a 1.45 Å crystal structure of the E. faecalis AtlA catalytic domain that reveals a closed conformation of a conserved β-hairpin and a complex network of hydrogen bonds that bring two catalytic residues to the ideal distance for an inverting mechanism. Based on the model of the AtlA–substrate complex, we identify key residues critical for substrate recognition and septum cleavage during bacterial growth. We propose that this work will provide useful information for the rational design of specific inhibitors targeting this enterococcal virulence factor and its orthologs in other pathogens.     

右美托咪定联合帕瑞昔布钠对老年腹腔镜胃癌手术患者应激反应、细胞免疫功能和认知功能的影响

摘要 目的：探讨帕瑞昔布钠和右美托咪定联合麻醉对老年腹腔镜胃癌手术患者细胞免疫功能、应激反应和认知功能的影响。方法：纳入2019年8月~2022年7月期间西安交通大学第二附属医院收治的150例老年腹腔镜胃癌手术患者。按照随机数字表法将患者分为帕瑞昔布钠组（n=50,帕瑞昔布钠）、右美托咪定组（n=50,右美托咪定）和联合组（n=50,右美托咪定联合帕瑞昔布钠）。对比三组临床指标、视觉模拟评分法（VAS）、简易精神状态检查表（MMSE）评分、术后认知功能障碍（POCD）发生率、应激反应指标[皮质醇（Cor）、肾上腺素（E）、促肾上腺皮质激素（ACTH）]、细胞免疫功能变化情况。结果：联合组的术后住院天数、肛门排气时间短于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组术后12 h、术后24 h、术后48 h VAS评分低于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组术后24 h、术后72 h MMSE评分高于右美托咪定组、帕瑞昔布钠组（P<0.05）。联合组的POCD发生率低于右美托咪定组、帕瑞昔布钠组（P<0.05）。三组术后1 d Cor、E、ACTH升高,但联合组低于帕瑞昔布钠组、右美托咪定组同期（P<0.05）。三组术后1 d CD8⁺升高,但联合组低于帕瑞昔布钠组、右美托咪定组同期;CD3⁺、CD4⁺、CD4⁺CD8⁺下降,但联合组高于帕瑞昔布钠组、右美托咪定组同期（P<0.05）。结论：右美托咪定联合帕瑞昔布钠应用于老年腹腔镜胃癌手术患者,镇痛效果显著,可减轻机体的应激反应、免疫抑制及对认知功能的损害。     

益肾活血汤联合百令胶囊对慢性肾功能衰竭患者肾功能、钙磷代谢和T淋巴细胞亚群的影响

摘要 目的：探讨益肾活血汤联合百令胶囊对慢性肾功能衰竭患者肾功能、钙磷代谢和T淋巴细胞亚群的影响。方法：选取2020年5月~2022年3月期间上海中医药大学附属曙光医院收治的102例慢性肾功能衰竭患者,按随机数字表法分为对照组（常规西医治疗）和观察组（常规西医治疗联合益肾活血汤和百令胶囊治疗）,各51例。两组均治疗8周。对比两组疗效及治疗前、治疗8周后中医证候积分、肾功能、钙磷代谢和T淋巴细胞亚群的变化。结果：观察组治疗8周后的临床总有效率为92.16%（47/51）,高于对照组的74.51%（38/51）（P<0.05）。治疗8周后,两组中医主证积分、次证积分均较治疗前下降,且相比于对照组,观察组更低（P<0.05）。治疗8周后,血肌酐、尿素氮、24 h尿蛋白在两组中均较治疗前下降,且观察组低于对照组（P<0.05）。治疗8周后,两组CD8⁺较治疗前下降,且观察组低于对照组（P<0.05）,而CD4⁺、CD3⁺、CD4⁺/CD8⁺均较治疗前升高,且观察组高于对照组（P<0.05）。治疗8周后,两组血磷、钙磷乘积下降,且观察组低于对照组（P<0.05）,血钙均升高,且观察组高于对照组（P<0.05）。结论：益肾活血汤联合百令胶囊治疗慢性肾功能衰竭患者,可提高肾功能,改善钙磷代谢和T淋巴细胞亚群,并缓解其临床症状,疗效确切,值得临床借鉴应用。     

脓毒症患者发生凝血功能紊乱的临床特征及预后影响因素分析

摘要 目的：探究脓毒症患者发生凝血功能紊乱的临床特征及预后影响因素。方法：选择2019年9月~2023年1月本院收治的80例脓毒症患者为本次研究对象,对所有患者开展凝血功能检验,并依据检验结果,将患者分为凝血功能异常组（n=60）及正常组（n=20）,分析凝血功能障碍异常及正常患者临床特征、凝血功能障碍异常及正常患者病情严重程度,并依据脓毒症患者预后,将其分为存活组（n=64）及死亡组（n=16）脓毒症患者预后的单因素与多因素Logistic回归分析。结果：凝血功能正常组及异常组平均动脉压、体温、白细胞计数（WBC）、纤维蛋白原（FIB）、凝血酶时间（TT）指标水平无较大差异（P＞0.05）,与凝血功能正常组比较,凝血功能异常组患者呼吸、脉率、降钙素原（PCT）、C反应蛋白（CRP）指标水平相对较高,部分凝血活酶时间（APTT）、凝血酶原时间（PT）指标水平相对较长,PLT指标水平相对较高（P＜0.05）;与凝血功能正常的脓毒症患者相比较,凝血功能异常患者急性肾损伤（AKI）及急性呼吸窘迫综合征（ARDS）发生率、急性生理与慢性健康评分（APACHE Ⅱ）及急性生理功能评分（SOFA）评分更高,住ICU时间均相对较长（P＜0.05）,机械通气及住院时间比较（P＞0.05）;脓毒症患者预后影响因素分析中,结果显示,年龄、体质量指数（BMI）、性别、糖尿病史、高血压病史均未对脓毒症患者预后产生较大影响（P＞0.05）,PT、PCT、APTT、CRP、SOFA评分及APACHE Ⅱ评分对脓毒症预后产生严重影响,死亡组患者各指标水平均高于存活组（P＜0.05）;将影响脓毒症患者预后的单因素予以赋值,纳入Logistic回归分析,以PCT、PT、APTT、CRP、SOFA、APACHE Ⅱ 评分为自变量,结果显示,PCT、PT、CRP、SOFA、APACHE Ⅱ 评分是影响脓毒症患者预后的独立危险因素（P＜0.05）。结论：脓毒症患者发生凝血功能紊乱会对临床相关指标产生影响,从而增加疾病严重程度,依据脓毒症患者预后,研究结果显示,PT、PCT、CRP、SOFA及APACHE Ⅱ评分均会对脓毒症患者预后产生不良影响,检验上述指标水平,可为临床评估脓毒症预后提供一定参考价值。     

对比分析IPS e.max Press铸瓷高嵌体与普兰梅卡CADCAM系统制作的高嵌体修复后牙牙体缺损的效果

摘要 目的：本研究旨在探讨对比分析IPS e.max Press铸瓷高嵌体与普兰梅卡CADCAM系统制作的高嵌体修复后牙牙体缺损的效果。方法：以2021年8月-2022年8月我院诊治的60例（86颗）后牙牙体缺损患者为研究对象,采用随机数字表法将其分为研究组（给予普兰梅卡CADCAM系统制作的高嵌体修复）和对照组（给予IPS e.max Press铸瓷高嵌体修复）各30例,对比两组修复前及修复1年后咀嚼功能、牙龈情况、RANK、CXCL16水平、IL-6、IL-8水平,统计修复结果及美牙效果满意度。结果：（1）修复前,两组咀嚼功能比较无差异（P＞0.05）;修复1年后,研究组咀嚼功能优于对照组（P＜0.05）;（2）修复前,两组牙龈指数、菌斑指数评分比较无差异（P＞0.05）;修复1年后,研究组牙龈指数、菌斑指数评分优于对照组（P＜0.05）;（3）修复前,两组RANK、CXCL16水平比较无差异（P＞0.05）;修复1年后,研究组RANK、CXCL16水平低于对照组（P＜0.05）;（4）修复前,两组IL-6、IL-8水平比较无差异（P＞0.05）;修复1年后,研究组IL-6、IL-8水平与对照组比较（P＞0.05）;（5）修复1年后,研究组修复体边缘适合性、修复体邻面解剖形态优于对照组（P＜0.05）;两组修复体表面及边缘着色、修复体折裂与固位比较,差异不显著（P＞0.05）;（6）修复1年后,研究组美牙效果满意度优于对照组（P＜0.05）。结论：与IPS e.max Press铸瓷高嵌体相比,普兰梅卡CADCAM系统制作的高嵌体修复后牙牙体缺损的效果更佳,能够提高咀嚼功能,改善牙龈指数,提高美牙效果满意度。     

高压氧联合高频rTMS对重型颅脑损伤后意识障碍患者促醒作用、神经电生理和脑损伤标志物的影响

摘要 目的：探讨高压氧联合高频重复经颅磁刺激（rTMS）对重型颅脑损伤后意识障碍（DOC）患者促醒作用、神经电生理和脑损伤标志物的影响。方法：选取2021年6月~2023年6月期间安徽中医药大学附属六安医院收治的的80例重型颅脑损伤后DOC患者。根据随机数字表法分为对照组（n=40,高压氧治疗）和观察组（n=40,高压氧联合高频rTMS治疗）。对比两组疗效、促醒作用、神经电生理和脑损伤标志物水平变化情况。结果：观察组的临床总有效率高于对照组（P<0.05）。两组治疗4周后修订的昏迷恢复量表（CRS-R）、格拉斯哥昏迷量表（GCS）评分升高,观察组高于对照组（P<0.05）。两组治疗4周后脑干听觉诱发电位（BAFP）、四肢体感诱发电位（SEP）、脑电图（EEG）分级有所改善,观察组改善效果优于对照组（P<0.05）。两组治疗4周后髓鞘碱蛋白（MBP）、神经元特异性烯醇化酶（NSE）、S100β蛋白下降,观察组低于对照组（P<0.05）。结论：高压氧联合高频rTMS治疗可有效促醒重型颅脑损伤后DOC患者,还可改善神经电生理活动,减轻脑损伤程度。     

小儿肺热咳喘颗粒联合雾化吸入用乙酰半胱氨酸溶液对支气管肺炎患儿肺通气功能、炎症因子和免疫球蛋白的影响

摘要 目的：观察小儿肺热咳喘颗粒联合雾化吸入用乙酰半胱氨酸溶液对支气管肺炎患儿肺通气功能、炎症因子和免疫球蛋白的影响。方法：选择2019年9月-2023年1月期间合肥市第二人民医院收治的100例支气管肺炎患儿,采用双色球法将患儿分为对照组和研究组,各为50例。对照组患儿接受雾化吸入用乙酰半胱氨酸溶液,研究组患儿在对照组的基础上接受小儿肺热咳喘颗粒。对比两组临床症状、炎症因子水平[白细胞介素-6（IL-6）、降钙素原（PCT）、C反应蛋白（CRP）]、免疫球蛋白[免疫球蛋白（Ig）A、IgM、IgG]、肺通气功能指标[吸气时间（TI）、呼气时间（TE）、吸呼比（TI/TE）、达峰时间比（TPF%TE）、达峰容积比（VPF%VE）]和不良反应发生率。结果：与对照组相比,研究组的肺部湿啰音消失时间、咳嗽消失时间、咳痰消失时间、退热时间更短（P<0.05）。研究组治疗10 d后CRP、IL-6、PCT低于对照组（P<0.05）。研究组治疗10 d后IgA、IgM、IgG高于对照组（P<0.05）。研究组治疗10 d后VT、TI、TE、TI/TE、TPF%TE、VPF%VE高于对照组（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：小儿肺热咳喘颗粒联合雾化吸入用乙酰半胱氨酸溶液治疗支气管肺炎,可有效缩短临床症状缓解时间,改善肺通气功能,降低炎症因子水平,调节免疫球蛋白,且安全性较好。