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In this paper, a two-dimensional (2D) thermo-hydro-mechanical dynamic (THMD) coupling analysis in the presence of a half-space medium is studied using Ezzat's fractional order generalized theory of thermoelasticity. Using normal mode analysis (NMA), the influence of the anisotropy of the thermal conduction coefficient, fractional derivatives, and frequency on the THMD response of anisotropy, fully saturated, and poroelastic subgrade is then analyzed with a time-harmonic load including mechanical load and thermal source subjected to the surface. The general relationships among the dimensionless physical variables such as the vertical displacement, excess pore water pressure, vertical stress, and temperature distribution are graphically illustrated. The NMA method does not require the integration and inverse transformation, increases the decoupling speed, and eliminates the limitation of numerical inverse transformation. The obtained results can guide the geotechnical engineering construction according to different values of load frequency, fractional order coefficient, and anisotropy of thermal conduction coefficient. This improves the subgrade stability and enriches the theoretical studies on thermo-hydro-mechanical coupling.

Both hydrogen sulfide (H2S) and sulfur dioxide (SO2) are produced endogenously from the mammalian metabolic pathway of sulfur-containing amino acids and play important roles in several vascular diseases. However, their interaction during the control of vascular function has not been fully clear. Here, we investigated the potential role of H2S in SO2 production and vascular regulation in vivo and in vitro. Wistar rats were divided into the vehicle, SO2, DL-propargylglycine (PPG) + SO2, β-cyano-L-alanine (BCA) + SO2 and sodium hydrosulfide (NaHS) + SO2 groups. SO2 donor was administered with or without pre-administration of PPG, BCA or NaHS for 30 min after blood pressure was stabilized for 1 h, and then, the change in blood pressure was detected by catheterization via the common carotid artery. Rat plasma SO2 and H2S concentrations were measured by high performance liquid chromatography and sensitive sulfur electrode, respectively. The isolated aortic rings were prepared for the measurement of changes in vasorelaxation stimulated by SO2 after PPG, BCA or NaHS pre-incubation. Results showed that the intravenous injection of SO2 donors caused transient hypotension in rats compared with vehicle group. After PPG or BCA pretreatment, the plasma H2S content decreased but the SO2 content increased markedly, and the hypotensive effect of SO2 was significantly enhanced. Conversely, NaHS pretreatment upregulated the plasma H2S content but reduced SO2 content, and attenuated the hypotensive effect of SO2. After PPG or BCA pre-incubation, the vasorelaxation response to SO2 was enhanced significantly. While NaHS pre-administration weakened the SO2-induced relaxation in aortic rings. In conclusion, our in vivo and in vitro data indicate that H2S negatively controls the plasma content of SO2 and the vasorelaxant effect under physiological conditions.

ObjectivesThe expression/activation of IL-6, p-Stat3, PD-1 and PD-L1 in gastric cancer (GC) tissues were examined to evaluate their abilities in predicting the survival prognosis in postoperative patients with GC.MethodsThe clinicopathological data and paraffin-embedded tissues of 205 patients who underwent gastric cancer resection were collected at the First Affiliated Hospital of Shihezi University School of Medicine, and the patients were followed-up annually after surgery. Immunohistochemistry (IHC) was used to detect the expression of IL-6, p-Stat3, PD-1 and PD-L1 proteins using tissue microarrays derived from these patients. Statistical analyses were performed using non-parametric tests, Spearman's correlation, ROC curves, Kaplan-Meier survival analysis, Cox single-factor and multifactor regression models. In comparison, the analyses were also performed for GC patients from public databases (407 patients from TCGA and 433 patients from GEO, respectively).Results(1) The expression levels of IL-6, p-Stat3, PD-1 and PD-L1 in GC tissues were significantly higher than adjacent normal tissues (ANT) (81.01% vs. 52.78%, P0.05). The lower the degree of cell differentiation (PConclusions(1) The expressed levels of IL-6, p-Stat3, PD-1 and PD-L1 are higher in GC tissues than in adjacent normal tissues. (2) The high levels of IL-6, p-Stat3 and PD-L1 are correlated with poor survival in GC patients. (3) The high levels of IL-6, p-Stat3, PD-1 and PD-L1 have influences in GC tumor microenvironment. (4) The multi-predictor combination of "IL-6+p-Stat3+PD-1+cell differentiation" serves as an optimal survival predictor for postoperative GC patients and better than the TNM staging system. As these molecules can be examined in preoperative biopsies, these observations may provide a useful guide for clinicians to strategize individualized surgical plans for GC patients before surgery.

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89–4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61–1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

Purpose Taiwan has implemented an integrated prospective payment program (IPP) for prolonged mechanical ventilation (PMV) patients that consists of four stages of care: intensive care unit (ICU), respiratory care center (RCC), respiratory care ward (RCW), and respiratory home care (RHC). We aimed to investigate the life impact on family caregivers of PMV patients opting for a payment program and compared different care units. Method A total of 610 questionnaires were recalled. Statistical analyses were conducted by using the chi-square test and multivariate logistic regression model. Results The results indicated no associations between caregivers’ stress levels and opting for a payment program. Participants in the non-IPP group spent less time with friends and family owing to caregiver responsibilities. The results of the family domain show that the RHC group (OR = 2.54) had worsened family relationships compared with the ICU group; however, there was less psychological stress in the RCC (OR = 0.54) and RCW (OR = 0.16) groups than in the ICU group. In the social domain, RHC interviewees experienced reduced friend and family interactivity (OR = 2.18) and community or religious activities (OR = 2.06) than the ICU group. The RCW group felt that leisure and work time had less effect (OR = 0.37 and 0.41) than the ICU group. Furthermore, RCW interviewees (OR = 0.43) were less influenced by the reduced family income than the ICU group in the economic domain. Conclusions RHC family caregivers had the highest level of stress, whereas family caregivers in the RCW group had the lowest level of stress.