Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy in postmenopausal women with persistent HPV infection with or without cervical and vaginal low-grade squamous intraepithelial lesions (CIN1/VaIN1)

ObjectiveTo analyze the efficacy and safety of photodynamic therapy (PDT) on postmenopausal women with persistent human papillomavirus (HPV) infection with or without low-grade cervical and vaginal intraepithelial neoplasia (CIN1 and VaIN1).Materials and methodsThe clinicopathological and follow-up data of 86 postmenopausal women with HPV infection (35 cases with chronic cervicitis and 51 cases with CIN1/VaIN1) were collected. All the women in this group met these criteria: menopausal time ≥ 1 year, HPV infection time ≥ 2 years, colposcopy and pathological diagnosis of biopsy ≤ CIN1/VaIN1 before PDT treatment, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with a week interval. The above patients were followed up 6 months and 12 months after PDT treatment, and the follow-up contents included HPV typing, cytology, colposcopy and pathological examinations. HPV negative conversion rate and lesion remission rate are the evaluation indicators of treatment efficacy. In addition, we also assessed the safety of PDT treatment.ResultsAt 12-month follow-up, the overall HPV clearance rate was 60% (45/75), of which the negative conversion rate of 16/18 HPV was 41.38% (12/29), and non-16/18 HPV was 71.74% (33/46) (p = 0.009). In patients without lesions, the HPV clearance rate was 51.72% (15/29), while in patients with CIN1/VaIN1 (n = 46), the HPV complete remission rate and lesion regression rate were 65.22% (30/46) and 89.13% (41/46), respectively. In addition, the clearance rate of HPV in lesion regression group was significantly higher than that in lesion persistence/progression group (0.00% vs. 73.17%, p = 0.003). The adverse reactions after PDT treatment were mild, mainly manifested as increased vaginal secretions or burning/tingling.ConclusionsPhotodynamic therapy can significantly enhance the elimination rate of persistent HPV infection in postmenopausal women and reduce the progression of CIN1/VaIN1. It could be an effective conservative treatment for persistent HPV infection and CIN1/VaIN1 in postmenopausal women.     

Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.     

妊娠合并自发性卵巢过度刺激综合征一例

卵巢过度刺激综合征是辅助生殖技术常见的并发症,通常在排卵后2周或2周以上发生。然而自发性卵巢过度刺激综合征极其罕见,一些病例报道表明,自发性卵巢过度刺激综合征的发生与卵泡刺激素受体突变、高人绒毛膜促性腺激素水平、高促甲状腺激素水平、促性腺激素垂体腺瘤等有关。现报告1例双胎妊娠合并自发性卵巢过度刺激综合征的病例,并进一步探讨自发性卵巢过度刺激综合征的可能病因、诊断和治疗原则。     

单孔胸腔镜下肺癌术后胸腔引流时间的影响因素分析北大核心

目的:探讨单孔胸腔镜下肺癌手术术后胸腔引流时间的影响因素。方法:本研究采用回顾性分析方法,回顾我院2018年01月至2019年12月原发性肺癌患者经单孔胸腔镜手术治疗的病例199例。按照术后胸腔引流时间分为两组,Ⅰ组(术后胸腔引流时间<5天)和Ⅱ组(术后胸腔引流时间≥5天)。对于影响术后胸腔引流时间的可能因素在两组间先采用单因素分析的方法筛选,再将筛选出来的对术后胸腔引流时间可能有意义的影响因素进行二项Logistic多因素回归分析。结果:经单因素分析及二项Logistic多因素回归分析结果显示:年龄≥60岁、手术部位、肺段切除术、胸膜粘连、手术时间≥180 min、术后早期下床活动是术后胸腔引流时间的独立影响因素(P<0.05)。结论:对于具有多个延长术后胸腔引流时间的独立影响因素的患者,应制定个体化管理方案,尽可能减少术后胸腔引流时间,减少住院天数,加快患者康复。     

HLA-B evolutionary divergence is associated with outcomes after SARS-CoV-2 infection

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham’s distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control.