摘要
Objective To establish a nomogram prediction model of hyperuricemia(HUA)onset risk in overweight and obese children and adolescents in order to provide reference for the prevention and treatment of HUA in this population.Methods The clinical data of 1 410 overweight and obese children and adolescents aged 6-17 years old visiting in this hospital from September 2021 to August 2022 were retrospectively analyzed.A total of 987 overweight and obese children and adolescents were randomly extracted according to a ratio of 7:3 to establish the model,and the remaining 423 cases were validated internally.Referring to the definition of high uric acid in"Zhu-futang Practical Pediatrics",the subjects were divided into high uric acid group and non-high uric acid group.The logis-tic regression analysis was used to analyze the influencing factors of HUA in overweight and obese children and adoles-cents.The nomogram model was constructed by using the R language.The area under the receiver operating character-istic(ROC)curve(AUC),decision analysis curve(DIC),clinical impact curve(CIC)and C-index were used to evalu-ate the predictive ability of the model,and the Bootstrap repeated sampling method(taking samples for 1000 times)was used for internal validation of the model.Results The results of multivariate analysis showed that the age(OR=2.324,95％CI:1.155-4.672,P=0.018),gender(OR=0.456,95％CI:0.256-0.810,P=0.007),triglycerides(OR=3.775,95％CI:2.321-6.138,P＜0.001),blood calcium(OR=26.986,95％CI:3.186-228.589,P=0.003)and blood creatinine(OR=1.047,95％CI:1.026-1.070,P＜0.001)were the influen-cing factors of HUA in overweight and obese children and adolescents.AUC of the ROC curve of the model was 0.840,the sensitivity was 0.786,the specificity was 0.762,the Youden index was 0.548,and the C-index was 0.840.The risk probability of DC A was 0.1-0.8,the net benefit rate of both models was＞0,AUC of ROC curve in the internal verification was 0.871.Conclusion The constructed nomogram in this study has a good predictive efficiency for the onset risk of HUA in overweight and obese children and adolescents,and may provide reference for the early diagnosis and treatment of this population.
摘要
The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.
摘要
Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.
摘要
Objective To investigate the expression profile variation of long non-coding RNAs (lncRNAs) in ankylosing sporidylitis (AS) and explore the role of lncRNAs in the pathogenesis of AS.Methods The peripheral blood mononuclear cells of AS patients and health controls (HC) were used to detect for differently expressed lncRNAs by microarray.The roles of lncRNAs were predicted with GO and pathway analysis.The results were verified by real time-polymerase chain reaction (PCR).Results A total of 148 lncRNAs and 134 mRNAs were detected,which had more than 2-fold differentially expressed in AS patients.Bioinformatics analysis found that GO term enrichment included protein binding,regulation of transcription,metabolism,signal transduction,et al.and might involve in toll-like receptor pathway,protein kinase,complement pathway,notch signaling pathway and so on.The expressions of three lncRNAs were estimated by real time-PCR which found that consistent with that of microarrays.Among these,D90064 was the most aberrantly expressed lncRNAs.Conclusions Several lncRNAs expression was changed significantly in AS patients in comparison with HC,which implies that those different lncRNAs may have an important role in the development and progression of AS.