Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy.Case DescriptionA 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up.ConclusionsWe, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient

A new quasi-Newton pattern search method based on symmetric rank-one update for unconstrained optimization

AbstractThis paper proposes a new robust and quickly convergent pattern search method based on an implementation of OCSSR1 (Optimal Conditioning Based Self-Scaling Symmetric Rank-One) algorithm [M.R. Osborne, L.P. Sun, A new approach to symmetric rank-one updating, IMA Journal of Numerical Analysis 19 (1999) 497–507] for unconstrained optimization. This method utilizes the factorization of approximating Hessian matrices to provide a series of convergent positive bases needed in pattern search process. Numerical experiments on some famous optimization test problems show that the new method performs well and is competitive in comparison with some other derivative-free methods

Limit Cycles Appearing From Piecewise Smooth Perturbations to a Reversible Nonlinear Center

This paper deals with the limit cycle bifurcation from a reversible differential center of degree [Formula: see text] due to small piecewise smooth homogeneous polynomial perturbations. By using the averaging theory for discontinuous systems and the complex method based on the Argument Principle, we obtain lower and upper bounds for the maximum number of limit cycles bifurcating from the period annulus around the center of the unperturbed system. </jats:p

Identification of Biomarkers Associated with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy Using WGCNA and Machine Learning Algorithms

Background. The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease. Methods. Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using “Metascape”. Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database. Results. We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated. Conclusion. As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF

Comparison of Clinical Outcomes Between Ticagrelor and Clopidogrel in Acute Coronary Syndrome: an Updated Meta-Analysis

Abstract Background: Ticagrelor is currently recommended for patients with acute coronary syndrome (ACS). However, recent studies have yielded controversial results. Objective: To compare the clinical outcomes of ticagrelor and clopidogrel in ACS patients.Methods: Three electronic databases were queried until April 1, 2021. Major adverse cardiovascular event (MACE) was the primary efficacy endpoint. The secondary efficacy endpoints included stroke, stent thrombosis (ST), cardiovascular (CV) death, all-cause death, and myocardial infarction (MI). The safety endpoints were (major and minor) bleeding. Odds ratios (ORs) and 95% confidence intervals (CIs) and were calculated to represent the estimated effect sizes.Results: Nine clinical trials and 18 observational studies with 269,935 ACS patients were included. No significant difference was detected in MACE (OR 0.76, 95% CI 0.54-1.06, p = 0.11, I² = 66.74%), but ticagrelor introduced a higher risk of bleeding (1.49, 1.14-1.94, 0.00, 63.97%) and minor bleeding (1.57, 1.08-2.30, 0.02, 59.09%) in clinical trials. The secondary efficacy endpoints differed between clinical trials and observational studies. Subgroup analysis demonstrated that ticagrelor showed better therapeutic effects in patients underwent PCI (0.38, 0.23-0.63, 0.00, 0) than those intended for PCI (1.02, 0.70-1.49, 0.93, 68.99%). Meanwhile ticagrelor showed different therapeutic effects on ACS patients of different ethnicities and from different countries.Conclusion:This meta-analysis demonstrated that ticagrelor is not superior to clopidogrel in MACE but is associated with a higher risk of bleeding in ACS patients. Different PCI strategies, ethnicities, and countries may be the factors that contribute to different therapeutic efficacy of ticagrelor.</jats:p

Crystal structure of the poly[(1,10-phenanthroline-κ² <i>N</i>,<i>N</i>′)(μ₃-carboxylatophenoxyacetato-κ⁴ <i>O,O</i>′:<i>O</i>′′;<i>O</i>′′′)lead(II)] monohydrate, C₂₁H₁₆N₂O₆Pb

Abstract C21H16N2O6Pb, monoclinic, P21/c (no. 14), a = 8.3116(17) Å, b = 19.439(4) Å, c = 11.437(2) Å, β = 98.11(3)°, V = 1829.4(6) Å3, Z = 4, R gt (F) = 0.0485, wR ref (F 2 ) = 0.0895, T = 293(2) K.</jats:p

Comparison of Clinical Outcomes Between Ticagrelor and Clopidogrel in Acute Coronary Syndrome: A Comprehensive Meta-Analysis

BackgroundTicagrelor is currently recommended for patients with the acute coronary syndrome (ACS). However, recent studies have yielded controversial results.ObjectiveTo compare the clinical outcomes between ticagrelor and clopidogrel in patients with ACS.MethodsThree electronic databases were queried until April 25, 2021. We defined major adverse cardiovascular events (MACEs) as the primary efficacy endpoint. The secondary efficacy endpoints included stroke, stent thrombosis, cardiovascular death, all-cause death, and myocardial infarction. The safety endpoints were (major and minor) bleeding. Odds ratios (ORs) and 95% CIs were calculated to represent the estimated effect sizes.ResultsA total of 270,937 patients with ACS from 10 clinical trials and 18 observational studies were included. No significant difference was detected in MACE (OR 0.81, 95% CI 0.60–1.08, p = 0.15, I2 = 64.83%). However, ticagrelor introduced a higher risk of bleeding (1.46, 1.17–1.83, 0.00, 61.66%) and minor bleeding (1.71, 1.33–2.21, 0.00, 4.65%) in clinical trials. The results of secondary efficacy endpoints differed in the clinical trials and observational studies. Subgroup analysis demonstrated that ticagrelor showed better therapeutic effects in patients who underwent the percutaneous coronary intervention (PCI) (0.38, 0.23–0.63, 0.00, 0) than those intended for PCI (1.03, 0.76–1.38, 0.87, 64.26%). Meanwhile, ticagrelor showed different therapeutic effects on patients with ACS of different ethnicities and different countries.ConclusionThis meta-analysis demonstrated that ticagrelor is not superior to clopidogrel in MACE but is associated with a higher risk of bleeding in patients with ACS. Different PCI strategies, ethnicities, and countries may be the factors that contribute to different therapeutic effects of ticagrelor.Systematic Review RegistrationThis study is registered with PROSPERO (CRD42021251212).</jats:sec