Anti-arthritic effects of FasL gene transferred intra-articularly by an inducible lentiviral vector containing improved tet-on system

The objective of this study is to construct and identify an inducible lentiviral vector containing improved tet-on system and FasL gene and observe its effects on pristane-induced arthritis (PIA). FasL gene was amplified from the spleen of Lewis rats by RT-PCR. The tet-on system was improved with insertion of a chicken chromatin insulator (cHS4) element and an rtTA-dependent, tet-responsive element containing modifications of the tetO sequence (TRE-tight1). Pro-apoptosis effect of the vector pTREFasLcHS4V16 on synovial cells was evaluated by flow cytometer in vitro. Anti-arthritis effects of the vector on PIA after intra-articular injection were observed by clinical evaluation and joint histology. Cytokines in synovial tissue were measured by ELISA. The recombinant inducible lentiviral vector pTREFasLcHS4V16 was successfully constructed. The expression response and the pro-apoptosis effects of the vector were doxycycline dose-dependent. The vector injected intra-articularly attenuated the severity of PIA and decreased the level of cytokines in inflamed joints. pTREFasLcHS4V16 with an improved tet-on system can precisely regulate the expression of FasL gene and apoptosis. Anti-arthritis effects were observed after intra-articular injection of the inducible vector.     

Nano‐selenium attenuates nickel‐induced testosterone synthesis disturbance through inhibition of MAPK pathways in Sprague‐Dawley rats

The aim of this study was to investigate the protective effects of Nano‐Se against Ni‐induced testosterone synthesis disorder in rats and determine the underlying protective mechanism. Sprague‐Dawley rats were co‐treated with Ni (5.0 mg/kg, i.p.) and Nano‐Se (0.5, 1.0, and 2.0 mg/kg, oral gavage) for 14 days after which various endpoints were evaluated. The Ni‐induced abnormal pathological changes and elevated 8‐OHdG levels in the testes were attenuated by Nano‐Se administration. Importantly, decreased serum testosterone levels in the Ni‐treated rats were significantly restored by Nano‐Se treatment, particularly at 1.0 and 2.0 mg/kg. Furthermore, the mRNA and protein levels of testosterone synthetase were increased by Nano‐Se compared to the Ni group, whereas phosphorylated protein expression levels of mitogen‐activated protein kinase (MAPK) pathways were suppressed by Nano‐Se administration in the Ni‐treated rats. Overall, the results suggest that Nano‐Se may ameliorate the Ni‐induced testosterone synthesis disturbance via the inhibition of ERK1/2, p38, and JNK MAPK pathways.     

儿童急性坏死性脑病的影像学分析

目的分析儿童急性坏死性脑病(ANEC)的颅脑影像学特征,探讨其对临床的指导价值。方法回顾性分析2013年1月至2018年10月武汉儿童医院22例确诊为ANEC患儿的临床及影像资料。患儿病初均有高热,前驱感染后迅速出现神经功能恶化。首次影像检查中,所有患儿均行头颅MRI检查,其中6例MRI检查前行头颅CT检查。MRI随访中,4例失访,6例仅行1次短期随访(<14 d),12例接受1~2次短期及1~4次长期随访(>14 d)。影像学检查重点观察丘脑、脑干、脑白质和基底节区等部位,以及整个随访中是否有出血及软化灶形成。结果所有ANEC患儿的影像学表现中均累及双侧丘脑,其他对称病变部位包括大脑白质(14例)、基底节区(15例)、脑干(16例)、小脑(9例)、胼胝体(2例)和海马(1例),不对称病灶患儿3例,分别见于大脑白质(2例)及小脑(1例)。最典型的头颅MRI表现为急性期在表观扩散系数(ADC)图上,丘脑呈"三色模式"(中央高信号和周围低信号环,以及丘脑周围高信号)或"双色模式"(丘脑中央低信号及边缘高信号)。影像学随访中,MRI上出现出血、脑软化可能提示临床预后差。结论ANEC为快速进展型脑病,具有典型影像学特点,出血、脑软化可能提示不良预后。     

Occult olfactory neuroblastoma presenting with multiple bone metastases: a case report

Rationable:Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nasal cavity, the primary local symptoms are usually inconspicuous. Patients are often admitted to various specialties based on different primary symptoms, which may result in delayed diagnosis and even a misdiagnosis.Patient concerns:Here we report a case of ONB that presented initially as multiple ostealgia without any local symptoms of the tumor and primarily misdiagnosed as multiple myeloma. The patient was a 47-year-old female with bone pain at multiple sites. The initial diagnosis was considered as multiple myeloma. However, the morphologic examination of bone marrow suggested that the tumor cells originated from the nervous tissues. After the positron emission computed tomography scan, the primary lesion in the nasal cavity was located, and a biopsy was performed.Diagnosis:The final diagnosis of ONB was confirmed by histopathological tests.Interventions:The patient was treated with metronomic chemotherapy.Outcomes:The symptoms of bone pain were significantly relieved 3 months later. The emission computed tomography scan of the whole body bones and the magnetic resonance imaging of the head showed that the tumor size did not change significantly and proved a progression-free of the disease.Lessons:It is a reasonable strategy to identify the original latent tumor by a prompt positron emission computed tomography scan when the primary diagnosis indicates a metastatic disease, especially for the occult malignancies like ONB.     

Effectiveness of direct-acting antivirals in maintenance hemodialysis patients complicated with chronic hepatitis C

Hepatitis C virus (HCV) infection is very common in maintenance hemodialysis patients, causing high morbidity and mortality. This study aimed to evaluate the effectiveness and adverse events of direct-acting antivirals (DAAs) in maintenance hemodialysis patients complicated with chronic hepatitis C in real-world clinical practice.In this retrospective observational study, hemodialysis patients with chronic hepatitis C infection in the Third Central Hospital of Tianjin outpatient were screened, and appropriate treatment plans were selected accordingly. Totally 25 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks or 24 weeks were included. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indexes and adverse reactions during the treatment process were also assessed.A total of 25 cases met the eligibility criteria and provided informed consent. Except for 1 patient who discontinued the treatment due to gastrointestinal bleeding, the remaining 24 cases completed the treatment cycle with 100% rapid virologic response (RVR) and 100% SVR12, with no serious adverse reactions recorded.Maintenance hemodialysis patients complicated with chronic hepatitis C in Chinese real-world setting tolerate DAAs very well, with a viral response rate reaching 100%.     

Is nasal septal suturing an alternative technique to nasal packing?: A protocol for systematic review and meta-analysis

Background:Nasal septal suturing is a commonly used alternative treatment to nasal packing after septoplasty. Besides alleviating postoperative discomfort, extensive studies have shown that nasal septal suturing is more effective than nasal packing. However, its clinical benefits remain controversial.Methods:We will perform a systematic review of nasal packings effect-related outcome in comparison to nasal septum suture among septoplasty patients by searching 8 databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). All eligible studies will be screened against the inclusion and exclusion criteria. Two independent reviewers will extract the data. Moreover, Review Manage 5.3 will be used for quality assessment and data analysis. Then, the random effects model or fixed effects model will be applied according to the heterogeneity. In conformity with the GRADE criteria, the merits of the evidence and recommended strength will be assessed.Results:This protocol will guide subsequent systematic reviews and meta-analyses. The differences in efficacy between nasal septal suturing and nasal packing after septoplasty will be evaluated in terms of efficiency, adverse reaction, comfort degree, and other factors.Conclusion:This proposed study will explore the possibility of adopting nasal septal suturing as an alternative to nasal packing after septoplasty.OSF registration number:doi: 10.17605/OSF.IO/WF3GX.