Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

Objective To construct a prediction model for atrial fibrillation(AF)after pacemaker implantation based on clinical features and plasma atrial natriuretic peptide(ANP)and brain na-triuretic peptide(BNP).Methods A retrospective analysis was conducted on 242 patients under-going pacemaker implantation in our department from January 2020 to October 2023.According to the occurrence of postoperative AF or not,they were divided into an AF group(61 cases)and a non-AF group(181 cases).The risk factors of AF after pacemaker implantation were analyzed,and a risk prediction model of AF after pacemaker implantation was constructed based on clinical features and plasma ANP and BNP levels.Results The AF group had significantly advanced age,larger proportions of hypertension and coronary heart disease,larger left ventricular diameter,and higher ANP,BNP,IL-6 and IL-8 levels,but lower proportion of using calcium antagonists when compared with the non-AF group(P＜0.01).Binary logistic regression analysis showed that hy-pertension,coronary heart disease,ANP,BNP and IL-6 were risk factors(P＜0.05,P＜0.01),and taking calcium antagonists was protective factor for AF after pacemaker implantation(P＜0.05).Hosmer Lemeshow fitting test indicated the model had a good fitness(x2=7.264,P=0.508).ROC curve analysis showed that the area under curve(AUC)value of the risk model for AF after pacemaker implantation in the training set was 0.826(95％CI:0.768-0.884),with an accuracy of 79.3％(192/242),and the AUC value of the model in the validation set was 0.835(95％CI:0.733-0.938).Conclusion Our AF prediction model based on clinical features and plasma ANP and BNP had good performance,and can provide auxiliary reference in predicting AF in patients undergoing pacemaker implantation.

Objective To construct a prediction model for atrial fibrillation(AF)after pacemaker implantation based on clinical features and plasma atrial natriuretic peptide(ANP)and brain na-triuretic peptide(BNP).Methods A retrospective analysis was conducted on 242 patients under-going pacemaker implantation in our department from January 2020 to October 2023.According to the occurrence of postoperative AF or not,they were divided into an AF group(61 cases)and a non-AF group(181 cases).The risk factors of AF after pacemaker implantation were analyzed,and a risk prediction model of AF after pacemaker implantation was constructed based on clinical features and plasma ANP and BNP levels.Results The AF group had significantly advanced age,larger proportions of hypertension and coronary heart disease,larger left ventricular diameter,and higher ANP,BNP,IL-6 and IL-8 levels,but lower proportion of using calcium antagonists when compared with the non-AF group(P＜0.01).Binary logistic regression analysis showed that hy-pertension,coronary heart disease,ANP,BNP and IL-6 were risk factors(P＜0.05,P＜0.01),and taking calcium antagonists was protective factor for AF after pacemaker implantation(P＜0.05).Hosmer Lemeshow fitting test indicated the model had a good fitness(x2=7.264,P=0.508).ROC curve analysis showed that the area under curve(AUC)value of the risk model for AF after pacemaker implantation in the training set was 0.826(95％CI:0.768-0.884),with an accuracy of 79.3％(192/242),and the AUC value of the model in the validation set was 0.835(95％CI:0.733-0.938).Conclusion Our AF prediction model based on clinical features and plasma ANP and BNP had good performance,and can provide auxiliary reference in predicting AF in patients undergoing pacemaker implantation.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Through analysis of Lau Wan Yee's published papers,monographs,conference speeches,research designs / revisions for major hospitals in China,combined with analysis of articles revised by Academician Lau in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University for the past decade,authors came up with 9 points in Academician Lau's research ideas.Academician Lau has played a huge and leading role in improving clinical skills and scientific research levels,as well as in development and internationalization of hepatobiliary and pancreatic surgery in China.To summarize the research ideas of Lau is of great importance to the future generations of surgeons.

Objective To study the effects of CTLA4-Ig on mu rine allergic contact dermatitis.Methods Mice were exposed to DNFB to induce allergic contact dermatitis and were i njected with CTLA4-Ig.Ear swelling was measured 24h after antigen challenge.Splenocytes from treated mice were assayed for their ability to prolif erate in response to DNFB or FITC stimulation in vitro.Results Profound inhibition of contact hypersensitivity response(CHS )was shown by 69.7%in mice treated with CTLA4-Ig compared with mice treate d with PBS control.CT-LA4-Ig-treated mice displayed DNFB-specific tolerance,but exhibited a vigorous immune response to FITC when re-sensitizing 14days after the fir st challenge.Adoptive transfer of l ymphocytes from CTLA4-Ig-treated mice could induce inhibition of CHS in recipien t mice.Conclusions CTLA4-Ig can inhibit CHS by blocking B7/CD28co-stimulatory pathway,which provides a new way to suppress typeⅣallergic reaction.[