RIP1-dependent linear and nonlinear recruitments of caspase-8 and RIP3 respectively to necrosome specify distinct cell death outcomes

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.

Application of health education path in advanced schistosomiasis patients with splenomegaly in perioperative period / 中国血吸虫病防治杂志

Objective To evaluate the effect of health education path on advanced schistosomiasis patients with splenomega-ly in perioperative period. Methods A total of 60 advanced schistosomiasis patients with splenomegaly in perioperative period were randomly divided into an observation group and a control group (30 cases each group). The patients in the observation group were intervened by the nursing and health education from admission to discharge according to the standardized process of health education path,while those in the control group were implemented with the conventional health education. Then the satis-faction of nursing work,hospital stays,hospitalization expenses and mastery of health knowledge of the patients in the two groups were investigated and the results were compared. Results The satisfaction rates of nursing work of patients in the obser-vation group and the control group were 90%and 60%,respectively,the difference between them was statistically significant (χ2=7.57,P<0.05). The average hospitals stays of the above two groups were 14.0 ± 3.5 d and 19.0 ± 6.8 d(t=2.85,P<0.01),respectively,and the average hospitalization expenses were(1.5 ± 0.5)thousand Yuan and(2.2 ± 0.7)thousand Yuan (t=24.57,P<0.01),respectively,both of the differences were statistically significant. On the 10th day after surgery,the mas-tery rates of the health knowledge of the two groups were 96.7%and 50.0%,respectively,the difference was statistically signifi-cant(χ2=16.86,P<0.001). Conclusions The implementation of the health education path can promote the rehabilitation of advanced schistosomiasis patients with splenomegaly,and increase the satisfaction as well as improve the mastery of the health knowledge of the patients. Meanwhile,it also can cut down the hospital stays and save the hospitalization expenses.