Establishment and Preliminary Application of a Rapid Fluorescent Focus Inhibition Test (RFFIT) for Rabies Virus

The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immunity effect after vaccination against rabies. For RFFIT, CVS-11 was used as the challenge virus, BSR cells as the adapted cells, and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study. With reference to WHO and Pasteur RFFIT procedures, a micro-RFFIT procedure adapted to our laboratory was produced, and its specificity and reproducibility were tested. We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen). We analyzed the levels of RVNA, and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens. The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV, but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen. The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.

SR-BI expression regulates the gastric cancer tumor immune microenvironment and is associated with poor prognosis

Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.

胃癌行腹主动脉旁淋巴结清扫的研究进展

手术治疗是治疗胃癌的主要方式之一,标准的术中淋巴结清扫尤为重要。关于胃癌患者是否行腹主动脉旁淋巴结清扫(para-aortic lymph node dissection,PAND)仍存在争议。预防性PAND的意义被否定,但治疗性PAND的效果还有待进一步的研究去证实。术前化疗联合规范的手术治疗可能是未来进展期胃癌伴腹主动脉旁淋巴结转移的标准治疗模式。本文就胃癌行PAND的研究进行综述,以期为临床实践提供指导。

ROS-responsive&scavenging NO nanomedicine for vascular diseases treatment by inhibiting endoplasmic reticulum stress and improving NO bioavailability

Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduction of reactive oxygen species(ROS)at vascular injury sites would react with NO to produce damaging peroxynitrite(ONOO)species and limit the therapeutic effect of NO.Hence,we design a ROS-responsive NO nanomedicine(t-PBA&NO NP)with ROS scavenging ability to solve the dilemma of NO-based therapy.t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate(ECA)to the injury sites via collagen IV homing peptide.The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging,endoplasmic reticulum and mitochondrial regulation.It subsequently maximizes vascular modulation effects of NO,without production of harmful compounds,reactive nitrogen species(RNS).Therefore,it significantly increases competitiveness of human umbilical vein endothelial cells(HUVECs)over human aortic smooth muscle cells(HASMCs)both in vitro and in vivo.The strategy proved effective in inducing faster re-endothelialization,inhibiting neointimal formation and restoring vascular homeostasis.The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.

Therapeutic advances in atrial fibrillation based on animal models

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with age.Despite the high frequency of AF in clinical practice,its etiology and management remain elusive.To develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its pathogenesis.While spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options.This review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and treatment.The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics

Atrial fibrillation(AF)is the most prevalent cardiac arrhythmia seen in clinical settings,which has been associated with substantial rates of mortality and morbidity.However,clinically available drugs have limited efficacy and adverse effects.We aimed to investigate the mechanisms of action of andrographolide(Andr)with respect to AF.We used network pharmacology approaches to investigate the possible therapeutic effect of Andr.To define the role of Andr in AF,HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation(RES)and rabbits were pro-treated for 1 d before rapid atrial pacing(RAP).Apoptosis,myofibril degradation,oxidative stress,and inflammation were determined.RNA sequencing(RNA-seq)was performed to investigate the relevant mechanism.Andr treatment attenuated RAP-induced atrial electrophysiological changes,inflammation,oxidative damage,and apoptosis both in vivo and in vitro.RNA-seq indicated that oxidative phosphorylation played an important role.Transmission electron microscopy and adenosine triphosphate(ATP)content assay respectively validated the morphological and functional changes in mitochondria.The translocation of nuclear factor erythroid 2-related factor 2(Nrf2)to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex.In conclusions,this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1(HO-1)to promote mitochondrial bioenergetics.

An artificial neural network model for multi-flexoelectric actuation of Plates

Flexoelectric effect can be used to design actuators to control engi-neering structures including beams,plates,and shells.Multiple flexo-electric actuators method has the advantage of less stress concentration and better control effect,but the mode-dependent optimal actuator locations could influence the flexoelectric actuation effect significantly.In this work,a neural network model is established to study the optimal combinations of multiple flexoelectric actuators on a rectangular plate.In the physical model,an atomic force micro-scope(AFM)probe was employed to generate an electric field gradient in the flexoelectric patch,so that flexoelectric control force and moment can be obtained.Multiple flexoelectric actuators on the plate was considered.Case studies showed that the flexoelectricity induced stress mainly concentrate near the probe,the size and shape of the flexoelectric patch have limited effect on the actuation,hence,only the actuator positions were choosing as the input of the ANN model.Using the prediction of the neural network model,the driving effect of a large number of actuators at different positions can be quickly obtained,and the optimal position of the actuator can be analyzed more accurately.