We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.
The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.
Background China faces a major increase in cardiovascular disease, yet there is limited population-based data on risk factors, particularly in children. Methods and Results Fasting blood samples, anthropometry and blood pressure were collected on 9,244 children and adults aged ≥7 years in late 2009 as part of the national China Health and Nutrition Survey. Prevalent overweight, elevated blood pressure, and cardiometabolic risk factors: glucose, HbA1c, triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), and C-reactive protein (CRP) are presented. Results 11% of Chinese children and 30% of Chinese adults are overweight. Rates of diabetes, dyslipidemia, hypertension, and inflammation are high and increased with age and were associated with urbanization. Approximately 42% of children have at least one of the following: pre-diabetes or diabetes, hypertension, high TC, LDL-C, TG, and CRP and low HDL-C, as do 70% males and 60% females aged 18–40 years and >86% of males and females ≥40 years. Conclusions HbA1c findings suggest that as many as 29.4 million Chinese children and 415.8 million Chinese adults may be prediabetic or diabetic. The high prevalence in less urban areas and across all income levels suggests that cardiometabolic risk is pervasive across rural and urban China.
Objective Evidence suggests that CD274 (PD-L1, B7-H1) immune checkpoint ligand repress anti-tumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. Design We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses’ Health Study and Health Professionals Follow-up Study. We conducted multivariable ordinal logistic regression analyses to examine the association of tumour CD274 expression with CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+-cell density in tumour tissue, controlling for potential confounders including tumour status of microsatellite instability (MSI), CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Results CD274 expression in tumour cells or stromal cells (including immune cells) was detected in 731 (89%) or 44 (5%) cases, respectively. Tumour CD274 expression level correlated inversely with FOXP3+-cell density in colorectal cancer tissue (outcome) (Ptrend=0.0002). For a unit increase in outcome quartile categories, multivariable odds ratio in the highest (vs. lowest) CD274 expression score was 0.22 (95% confidence interval 0.10–0.47). Tumour CD274 expression was inversely associated with MSI-high status (P=0.001). CD274 expression was not significantly associated with CD3+, CD8+, or CD45RO+-cell density, pathological lymphocytic reactions, or patient survival prognosis. Conclusions Tumour CD274 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible influence of CD274-expressing carcinoma cells on regulatory T (Treg) cells in the tumour microenvironment.
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