Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

1. Download : Download high-res image (90KB)
2. Download : Download full-size image

     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

社会力量参与公立互联网医院建设激励与约束机制研究

社会力量具备相应的经济基础和技术条件,对于公立互联网医院体系建设具有积极的促进作用。但是实践中仍然存在商业模式不完善、监管制度不健全等问题。基于经济学契约理论要义,提出在坚持激励与约束机制并举、平衡公私益关系的前提下,通过完善医保政策、构建互联网医疗服务价格分类管理机制来促进社会力量向医疗服务公益性目标回归,并通过构建完善的监督体制来约束部分社会力量的盲目逐利性行为。     

Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

1. Download : Download high-res image (229KB)
2. Download : Download full-size image

     

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

The Fate and Relevance of the Patella in Two-Stage Revision Total Knee Arthroplasty for Periprosthetic Joint Infection

BackgroundIt remains unclear whether reimplantation of a patellar component during a two-stage revision for periprosthetic total knee arthroplasty infection (PJI) affects patient reported outcome measures (PROMs) or implant survivorship. The purpose of this study was to evaluate whether patellar resurfacing during reimplantation confers a functional benefit or increases implant survivorship after two-stage treatment for PJI.MethodsTwo-stage revisions for knee PJI performed by three surgeons at a single tertiary care center were reviewed retrospectively. All original patellar components and cement were removed during resection and the patella was resurfaced whenever feasible during reimplantation. PROMs, implant survivorship, and radiographic measurements (patellar tilt and displacement) were compared between knees reimplanted with a patellar component versus those without a patellar component.ResultsA total of 103 patients met the inclusion criteria. Forty-three patients (41.7%) underwent reimplantation with, and 60 patients (58.3%) without a patellar component. At a mean follow-up of 33.5 months, there were no significant differences in patient demographics or PROMs between groups (P ≥ .156). No significant differences were found in the estimated Kaplan-Meier all-cause, aseptic, or septic survivorship between groups (P ≥ .342) at a maximum of 75 months follow-up. There was no significant difference in the change (pre-resection to post-reimplant) of patellar tilt (P = .504) or displacement (P = .097) between the groups.ConclusionPatellar resurfacing during knee reimplantation does not appear to meaningfully impact postoperative PROMs or survivorship. Given the risk of potential extensor mechanism complications with patellar resurfacing, surgeons may choose to leave the patella without an implant during total knee reimplantation and expect similar clinical outcomes.Level of EvidenceLevel III.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.