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The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER [Ca2.sup.+]-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal [Ca2.sup.+] oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the [CD4.sup.+] T cell pool immune suppressive and caused it to behave in the same manner as [Foxp3.sup.+] Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient [CD4.sup.+] T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3- mediated [Ca2.sup.+] signaling inhibition may be a central effector mechanism of Treg immune suppression., Introduction The suppressive mechanism of Tregs remains a topic of continuing debate. Proposed mechanisms, including T cell cytolysis, surface protein extraction, local generation of adenosine, etc., all require Treg binding [...]

During the power operation of nuclear reactors, the corrosion products in the secondary circuit will deposit on the inside of Helical-coiled One-Through Steam Generator (H-OTSG) heat transfer tubes and form fouling. The main component of fouling is iron-based oxide, which generates from the heat exchangers made of cast iron. Fouling may change the local heat transfer characteristics of heat transfer tubes, and then affect the safety and economy of reactors. In order to obtain the distribution of fouling thickness and its action mechanism on helical tubes heat transfer characteristics, the heat transfer experiment under small pressurized reactors service environment was conducted. The experimental results indicate: corrosion products mainly deposit on onset of saturated boiling point with the maximum fouling thickness of 50 μm, and induce local wall temperature elevating about 773 K; fouling will increase the thermal equilibrium void fraction and hinder the heat transfer of helical tube, but has little impact on the onset position of saturated boiling point; corrosion products will release and re-deposit near dry-out point because of the flush of high speed vapor, causing the periodic fluctuation of thermal resistance of helical tube.

Objective To explore the relationship between the post-operative peak value of central venous pressure (CVPp) and the incidence of acute kidney injury (AKI) in patients who had undergone cardiopulmonary bypass surgery (CBS). Methods Clinical data were retrospectively collected from 1 May 2016 to 1 May 2018 from all patients undergoing CBS in the Department of Intensive Care Medicine, Peking Union Medical College Hospital. The CVP values immediately after transfer to ICU (CVP 0h) and at 6 h(CVP 6h), and CVPp within 48 h(CVPp 48h) of transfer to ICU, the incidence of AKI after 48 h of transfer to ICU and in-hospital mortality were recorded. The receiver operating characteristic (ROC) curve was used to evaluate the clinical value of CVP-related indicators in predicting AKI after CBS and determine the optimal threshold. The risk factors for AKI and in-hospital mortality after CBS were analysed using single factor and multifactorial Logistic regression. Results A total of 485 patients after CBS who met the inclusion and exclusion criteria were enrolled, with an incidence of AKI after 48 h of transfer to ICU of 25.2% (122/485) and an in-hospital mortality rate of 2.5% (12/485). The ROC curve analysis showed that the area under the curve (AUC) for CVPp 48h to predict AKI after CBS was 0.634 (95% CI: 0.577-0.692, P < 0.001), with an optimal threshold value of 14 mm Hg, sensitivity of 49.6% and specificity of 63.5%. Multifactorial logistic regression analysis showed that hypertension(OR=2.505, 95% CI: 1.581-3.969, P < 0.001), pulmonary hyperten-sion(OR=2.552, 95% CI: 1.573-4.412, P < 0.001), prolonged aortic block time(OR=1.009, 95% CI: 1.004-1.014, P=0.001), and CVPp 48h≥14 mm Hg(OR=1.613, 95% CI: 1.030-2.526, P=0.037) were independent risk factors for AKI after CBS; CVPp 48h≥14 mm Hg was an independent risk factor for in-hospital death(OR=8.044, 95% CI: 1.579-40.979, P=0.012). Conclusions CVPp 48h is associated with AKI in patients who have undergone CBS. The monitoring and management of CVP might be a way to improve the prognosis of these patients.

Hemodynamic optimization is key to resuscitation of critically ill patients in intensive medicine. Delayed or improper treatment will inevitably lead to hypoperfusion, tissue hypoxia and multiple organ failure, which affects the patients' outcome. Therefore, early identification of patients at risk and implementation of adequate monitoring and guidance intervention have a profound impact on the results. The key principle of hemodynamic management is to optimize blood flow and oxygen flow according to current tissue metabolism. To achieve this goal, we need to monitor and get blood pressure, cardiac output, organ-specific automatic regulation and tissue microcirculation. However, the clinical monitoring data is huge. At the same time nearly one hundred pieces of data objectively present the pathophysiological state of the patient, and the changes of data at different time periods can describe the progress of the patients' condition. Therefore, the integrated analysis of time/ frequency domain based on millisecond-level high-resolution data will promote the understanding and practice of hemodynamics at microcosmic level, and help to facilitate clearer judgment and more precise treatment of patients' condition.

With the continuous exploration of the pathophysiological mechanisms of critical illness, the host response, a 'bridge' between different etiologies and the development of critical illness, has received much attention. Host response is the focus of critical illness pathophysiology, and hemodynamics is the core of critical illness development. On the one hand, the host response has a significant impact on hemodynamics; on the other hand, the intervention of the host response through analgesic-sedative-anti-sympathetic therapy and the management of inflammation, immunity, coagulation, metabolism, and bioenergy can stabilize the hemodynamics and achieve the goal of critical illness treatment. A deepening understanding of host response not only enriches the connotation of hemodynamics but also facilitates further study and exploration of the pathophysiological mechanisms of critical illness. Therefore, we describe host response from three aspects: a new understanding of critical illness based on host response, the effect of host response on hemodynamics, and hemodynamic therapy based on the host response.

The change of organ hemodynamics in critical patients is key to the impairment of organ function. Organ perfusion pressure is the direct power to ensure organ blood flow, which is affected by inlet organ pressure (arterial pressure) and outlet organ pressure (venous pressure). Different organs have unique perfusion pressure requirements and regulation systems for blood flow adjustment to match their physiological needs. As the supply side of organ perfusion, the blood flow of organs is influenced by mean arterial pressure (MAP)and autoregulation system. Organs with different autoregulatory abilities have different requirements for MAP, so the appropriate MAP should be decided according to the autoregulation range in clinical practice. However, organ blood flow perfusion is not only determined by the supply side, but also affected by venous reflux. Changes in arteriovenous gradient across important organs affect organ blood flow perfusion. Different organs have different tolerance levels for venous reflux disorders because their distance from the heart and the specificity of the organ itself. When conducting hemodynamic intervention, physicians should pay attention to the influence of different pressure changes on organ perfusion.

An important milestone in human cognition of severe diseases began with a refined understanding of the hemodynamics of shock. After decades of development, the concept of hemodynamic therapy has become more perfect. The treatment of shock involves not only guided group therapy, but also bedside individualized strategies. The leading effect of blood flow has long been well understood, and the oxygen flux in the blood flow is the target index of hemodynamic resuscitation of shock. In this paper, we aim to further explore blood flow and blood oxygen flux, separate the influence factors of blood flow and oxygen flux, monitoring and recovery-guided treatment, and propose four subtypes based on blood flow and oxygen flux shock, with the hope of ushering in an era of more precise hemodynamic treatment for organ hemodynamic therapy.

Against the background of the increasing trend of fragmentation of freight demand, the spatial structure analysis of urban networks using road Less-Truck-Load (LTL) dedicated lines has positive implications for enriching the flow space theory and empirical evidence. Based on the social network analysis method, this study used the data of the national prefecture-level and above cities' road LTL dedicated lines on the China Communications Logistics LOGINK System in 2018, and conducted feature mining of Chinese city network relationships from the perspective of road LTL dedicated lines at three levels: city nodes, intercity connections, and sub-networks. The results show the following: (1) Shanghai, Tianjin, Zhengzhou, Guangzhou, and Hangzhou dominated the network. Based on the cargo flow organization coefficients, urban nodes can be divided into four types: strong center, second strong center, weak center, and subordinate. The number of high-grade cities in the network was relatively small and mainly concentrated in the eastern and central regions. The imbalance in the spatial distribution is obvious. (2) Among the top ten cities in terms of the amount of first contact, the ratio of export-oriented cities to import-oriented cities is 4:1, which reflects the imbalance in cargo flow. The network space carved by the road LTL dedicated lines data showed a significant distance attenuation law. The road LTL dedicated lines connections are mainly distributed in the intercity range of 0-200 km and the interprovincial range of 200-500 km, with the number of special lines concentrated in 500 km accounting for 41.9%. (3) The community detection algorithm was used to identify six urban communities with significant regional characteristics, including the Northeast Jilumeng, Zhongyuan, Guanzhong, Jianghuai, Pan-Pearl, Delta-Yangtze River Delta, and Changzhutan communities. The community structures showed clear spatial agglomeration and cross-administrative features. (4) To enhance the status of the nodes of the road LTL network and optimize the organization of the network space, the following suggestions are put forward: Urban networks based on the road LTL dedicated line data should enhance the service capacity of the Chengdu-Chongqing urban agglomeration road LDL line, strengthen the industrial agglomeration and driving role of core cities, optimize the industrial structure of marginal cities, strengthen the integration of transportation and industry, and actively guide the car-free carrier platform to improve the efficiency of road freight organization. In future studies, long-term cycles and multiple data sources should be enhanced to verify the validity and reliability of the findings.