Longistylin A,a natural stilbene isolated from the leaves of Cajanus cajan,exhibits significant anti-MRSA activity

Longistylin A (LLA) is an abundant stilbene isolated from the leaves of Cajanus cajan (L.) Millsp. However, the antibacterial effect of LLA is not yet understood. Therefore, in this study, a detailed investigation of the antibacterial effect of LLA, particularly against methicillin-resistant Staphylococcus aureus (MRSA), was conducted. In vitro, LLA exhibited strong antibacterial activity against MRSA with a minimum inhibitory concentration (MIC) of 1.56 µg/mL and displayed much more rapid bactericidal activity (3-log decrease in MRSA survival within 8 h) than vancomycin. A membrane-targeting experiment suggested that the antibacterial activity of LLA is associated with perturbation of the bacterial membrane potential and increased membrane permeability. Notably, LLA had relatively weak cytotoxicity to murine macrophages [50% cytotoxic concentration (CC₅₀) = 8.61 ± 0.57 µg/mL]. In vivo, topical treatment of a skin injury with LLA improved wound healing and closure in an MRSA-infected wound healing mouse model. After 3 days treatment, LLA decreased MRSA bacterial counts in the wounded region, reduced the accumulation of immune cells at the injury site, and alleviated induction of the inflammatory cytokines tumour necrosis factor-alpha (180.74 ± 10.78 pg/mL vs. 606.57 ± 68.99 pg/mL) and interleukin-6 (87.25 ± 10.19 pg/mL vs. 280.58 ± 42.27 pg/mL) in serum.     

Fusion protein His-Hsp65-6IA2P2 prevents type 1 diabetes through nasal immunization in NOD Mice

Human heat shock protein 60 (Hsp60), is an endogenous β-cells autoantigen, it could postpone the onset of insulitis and sooner type 1 diabetes mellitus. P277 is one of Hsp65 determinants at position 437–469 of amino acids cascaded. Meanwhile, it's already well-known that there were several better anti-diabetic B epitopes, such as insulinoma antigen-2 (IA-2). Currently, fusion protein IA2P2 has constructed in order to enhance its pharmacological efficacy. In addition, added homologous bacterial-derived Hsp65 and His tag were beneficial to protein immunogenicity and purification separately. So, finally we examined a fusion protein His-Hsp65-6IA2P2 could regulate Th2 immune response and reduce natural diabetic incidence in NOD mice. We constructed two express vector pET28a–His-Hsp65-6P277 and pET28a–His-Hsp65-6IA2P2. After purification, we observed that triple intranasal administration of these two fusion protein in 4-week-old NOD mice maintained normal blood glucose and weight, with a lower diabetic or insulitis incidence. Consistent with induced splenic T cells proliferation and tolerance, His-Hsp65-6IA2P2-treated mice performed reduced IFN-γ and increased IL-10 level. In conclusion, we suggested that fusion protein His-Hsp65-6IA2P2 could be reconstructed and purified successively. Furthermore, nasal administration of this fusion protein could rebalance T cells population and prevent T1DM.     

Effect of a Device-Free Compressed Shell Fixation Method on Hepatic Respiratory Movement: Analysis for Respiratory Amplitude of the Liver and Internal Motions of a Fiducial Marker

Purpose

Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.

Biodegradable versus titanium osteosynthesis in maxillofacial traumatology: a systematic review with meta-analysis and trial sequential analysis

Titanium osteosynthesis is currently the fixation system of choice in maxillofacial traumatology. Biodegradable osteosynthesis systems have the ability to degrade in the human body. The aim of this study was to conduct a systematic review, with meta- and trial sequential analyses, to assess the efficacy and morbidity of biodegradable versus titanium osteosynthesis after maxillofacial trauma. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials and prospective and retrospective controlled studies. Five time periods were studied: perioperative, short-term (0–4 weeks), intermediate (6–12 weeks), long-term (>12 weeks), and overall follow-up. After screening 3542 records, 24 were included. All had a high risk of performance and detection bias due to the nature of the interventions. Meta-analysis showed no differences in efficacy or morbidity between biodegradable and titanium osteosynthesis. The risk of perioperative screw breakage was significantly higher (risk ratio 17.13, 95% confidence interval 2.19–34.18) and the symptomatic plate removal rate lower in the biodegradable group (risk ratio 0.11, 95% confidence interval 0.02–0.57), which was confirmed by the trial sequential analysis. The quality of evidence ranged from very low to moderate. Based on the narrative review and meta-analyses, current evidence shows that biodegradable osteosynthesis is a viable alternative to titanium osteosynthesis when applied in the treatment of maxillofacial trauma, with similar efficacy but significantly lower symptomatic plate removal rates. Perioperative screw breakage occurred significantly more often in the biodegradable group compared to the titanium group.     

口腔医疗机构应对国家突发公共卫生事件的问题与思考

突发公共卫生事件应急管理是一个全球性的课题。本文就2019年12月以来发生在中国的新型冠状病毒肺炎这一突发公共卫生事件,口腔医疗机构及其从业人员面临的相关问题进行法律层面的分析与思考,以期对口腔医疗行业应对突发公共卫生事件提供帮助和指导。     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

p53-Induced inflammation exacerbates cardiac dysfunction during pressure overload

The rates of death and disability caused by severe heart failure are still unacceptably high. There is evidence that the sterile inflammatory response has a critical role in the progression of cardiac remodeling in the failing heart. The p53 signaling pathway has been implicated in heart failure, but the pathological link between p53 and inflammation in the failing heart is largely unknown. Here we demonstrate a critical role of p53-induced inflammation in heart failure. Expression of p53 was increased in cardiac endothelial cells and bone marrow cells in response to pressure overload, leading to up-regulation of intercellular adhesion molecule-1 (ICAM1) expression by endothelial cells and integrin expression by bone marrow cells. Deletion of p53 from endothelial cells or bone marrow cells significantly reduced ICAM1 or integrin expression, respectively, as well as decreasing cardiac inflammation and ameliorating systolic dysfunction during pressure overload. Conversely, overexpression of p53 in bone marrow cells led to an increase of integrin expression and cardiac inflammation that reduced systolic function. Norepinephrine markedly increased p53 expression in endothelial cells and macrophages. Reducing β₂-adrenergic receptor expression in endothelial cells or bone marrow cells attenuated cardiac inflammation and improved systolic dysfunction during pressure overload. These results suggest that activation of the sympathetic nervous system promotes cardiac inflammation by up-regulating ICAM1 and integrin expression via p53 signaling to exacerbate cardiac dysfunction. Inhibition of p53-induced inflammation may be a novel therapeutic strategy for heart failure.