Association of lymphocyte subsets with the efficacy and prognosis of PD­1 inhibitor therapy in advanced gastric cancer: results from a monocentric retrospective study.

PURPOSE: This retrospective study aimed to investigate the changes in peripheral blood lymphocyte subsets before and after immunotherapy in patients with advanced gastric cancer and their relationship n with the therapeutic efficacy and clinical prognosis. METHODS: Peripheral blood lymphocyte subsets, including CD4 + T cells, CD8 + T cells, CD4+/CD8 + ratio, NK cells, Treg cells, and B cells, were collected from 195 patients with advanced gastric cancer who were admitted to the First Hospital of Shanxi Medical University with immunotherapy from January 2020 to October 2021, at the time of diagnosis of advanced gastric cancer, before immunotherapy and after 3 cycles of immunotherapy. T-tests were used to examine the factors influencing the patients' peripheral blood lymphocyte subsets and the changes after immunotherapy. To examine the relationship between lymphocyte subsets and treatment outcomes, ROC curves were plotted using a logistic regression. Kaplan-Meier curve was drawn, and the Log Rank test was carried out to compare the differences in PFS between the different groups. Cox proportional hazards regression model was used to analyze the factors affecting PFS after calibration of other variables. RESULTS: The proportion of peripheral blood lymphocyte subsets in patients with advanced gastric cancer was affected by age and PD-L1 level. Compared to the baseline, the treatment effective group had higher proportions of CD4 + T cells, a higher CD4+/CD8 + ratio, NK cells and Treg cells, and lower proportions of CD8 + T cells and B cells in the peripheral blood after three cycles of immunotherapy. In the treatment-naive group, there were no significant differences in the lymphocyte subsets. With cut-off values of 30.60% and 18.00%, baseline CD4 + T cell and NK cell ratios were independent predictors of immunotherapy efficacy and PFS. Treg cell ratio, gender, PD-L1 levels, and MMR status all predicted PFS independently. CONCLUSION: The proportion of peripheral blood lymphocyte subsets was modified in patients who responded to PD-1 inhibitors. Different lymphocyte subpopulation levels can be used as biomarkers to predict immunotherapy efficacy and clinical prognosis in patients with advanced gastric cancer.

Relation Between Calcium-Phosphorus Product and Total Coronary Artery Occlusion in a Nonchronic Kidney Disease Population: A Cross-Sectional Study.

Excessive calcium-phosphorus product (Ca-P product) in patients with chronic kidney disease (CKD) is associated with coronary artery calcification and coronary artery disease, but the relation between Ca-P product and coronary artery disease in non-CKD populations has rarely been reported. Therefore, we designed a cross-sectional study to investigate the role of Ca-P product in total coronary artery occlusion (TCAO) in a non-CKD population. We reviewed 983 patients who underwent coronary angiography at Guangyuan Central Hospital from February 2018 to January 2020. Ca-P product (mg2/dl2) was calculated as Ca (mmol/L) × 4 × P (mmol/L) × 3.1 and was analyzed as a continuous and tertiary variable. TCAO was defined as complete occlusion of any coronary artery by coronary angiography (thrombolysis in myocardial infarction flow grade 0). Statistical analysis was performed using univariate and multivariate logistic regression models and restricted cubic splines. Univariate logistic regression analysis showed a statistically significant association between Ca-P product and TCAO (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95 to 0.99, p <0.001). After stepwise adjustment for covariates, the risk of TCAO was reduced by 40% in the high versus low Ca-P group (OR 0.6, 95% CI 0.38 to 0.95, p = 0.031), and the risk of TCAO was predicted to decrease by 4% (OR 0.96, 95% CI 0.94 to 0.99, p = 0.006) for each unit increase in Ca-P product. Restricted cubic splines showed a nonlinear relation between Ca-P product and TCAO, with a significant decrease in the risk of TCAO after reaching 27.46 (nonlinear p = 0.047). In conclusion, in non-CKD populations, a higher Ca-P product (≥27.46 mg2/dl2) may help avoid TCAO.

Peripheral blood nutrient indices as biomarkers for anti­PD­1 therapy efficacy and prognosis in patients with advanced gastric cancer.

Immunotherapy offers survival benefits for patients with advanced gastric cancer, but not all populations can benefit from immunotherapy. Good nutritional status is fundamental to a patient's immune function and may have an impact on the efficacy of immunotherapy. The present study aimed to investigate changes in prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and albumin-globulin ratio (AGR) values before and after immunotherapy in patients with advanced gastric cancer. The study also aimed to determine the potential association of the aforementioned values with patient outcomes and prognosis. Body mass index (BMI), serum albumin, total protein, peripheral blood lymphocyte, neutrophil, carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9) and a-fetoprotein (AFP) data were collected from 195 patients with advanced gastric cancer who underwent immunotherapy from January 2020 to October 2021. In addition, PNI, ALI and AGR values were calculated based on variables in blood collected from the patients within 3 days prior to immunotherapy and 3 weeks after immunotherapy. The results demonstrated that low PNI was associated with elevated CEA levels. Moreover, low ALI levels were associated with reduced BMI levels, elevated AFP levels, PD-L1 negative and first-line treatment. Comparison of responding and non-responding groups revealed that patients who responded to immunotherapy had higher PNI and AGR values than patients who did not respond, both before and after treatment, but had lower CEA and CA19-9 levels after treatment. Furthermore, in the non-responding group, PNI and AGR values were decreased and CEA values were increased following treatment compared with those prior to treatment. The objective response and disease control rates were higher in the high PNI and AGR groups compared with the low PNI and AGR groups, respectively. Moreover, PNI and AGR were found to be independent predictors of the short-term efficacy of immunotherapy for advanced gastric cancer, with cut-off values of 47.18 and 1.29, respectively. Univariate analysis revealed that ALI was associated with the progression-free survival (PFS) of patients, while multivariate analysis demonstrated that baseline PNI and AGR were independent predictors of PFS. In conclusion, tumor progression leads to a decline in the nutritional level of patients, and the present study indicated that effective immunotherapy may alleviate this deterioration to a certain extent. Furthermore, PNI and AGR exhibit potential in predicting the efficacy of immunotherapy and the prognosis of patients with advanced gastric cancer, and may exhibit potential as biomarkers in clinical practice.

Study on the Elastic-Plastic Correlation of Low-Cycle Fatigue for Variable Asymmetric Loadings.

The mean stress effect in fatigue life varies by material and loading conditions. Therefore, a classical low cycle fatigue (LCF) model based on mean stress correction shows limits in asymmetric loading cases in both accuracy and applicability. In this paper, the effect of strain ratio (R) on LCF life is analyzed and a strain ratio-based model is presented for asymmetric loading cases. Two correction factors are introduced to express correlations between strain ratio and fatigue strength coefficient and between strain ratio and fatigue ductility coefficient. Verifications are conducted through four materials under different strain ratios: high-pressure tubing steel (HPTS), 2124-T851 aluminum alloy, epoxy resin and AZ61A magnesium alloy. Compared with current widely used LCF models, the proposed model shows a better life prediction accuracy and higher potential in implementation in symmetric and asymmetric loading cases for different materials. It is also found that the strain ratio-based correction is able to consider the damage of ratcheting strain that the mean stress-based models cannot.

Performance Analysis of a Fiber Reinforced Plastic Oil Cooler Cover Considering the Anisotropic Behavior of the Fiber Reinforced PA66.

In this paper, a simulation method based on an orthogonal anisotropic material is proposed. A numerical example using a simple plate is presented to show the difference in the static performance between the orthogonal anisotropic and the isotropic models. Comparing with the tested modal data of a diesel engine oil cooler cover made by glass fiber reinforced polyamide 66 (PA66), the proposed simulation method was confirmed to be much closer to reality than the general isotropic model. After that, a comprehensive performance comparison between the plastic oil cooler covers with the orthogonal anisotropic and the isotropic fiber orientations was carried out including a static deformation and stress analysis under a pressure-temperature coupled load, a forced response analysis, and an acoustic analysis under real operating conditions. The results show that the stress, the deformation, the peak vibration velocity, and the overall sound power level of the orthogonal anisotropic model are different from that obtained with the isotropic model. More importantly, the proposed method can provide a much more detailed frequency content compared to the isotropic model.