Bifurcation analysis and optimal control of a network-based SIR model with the impact of medical resources

A new network-based SIR epidemic model, which incorporates the individual medical resource factor and public medical resource factor is proposed. It is verified that the larger the public medical resource factor, the smaller the control reproduction number, and the larger individual medical resource factor can weaken the spread of diseases. We found that the control reproduction number below unity is not enough to ensure global asymptotic stability of the disease-free equilibrium. When the number of hospital beds or the individual medical resource factor is small enough, the system will undergoes backward bifurcation. Moreover, the existence and uniqueness of the optimal control and two time-varying variables’s optimal solutions are obtained. On the scale-free network, the level of optimal control is also proved to be different for different degrees. Finally, the theoretical results are illustrated by numerical simulations. This study suggests that maintaining sufficient both public medical resources and individual medical resources is crucial for the control of infectious diseases

Integrated Thermal and Energy Management of Connected Hybrid Electric Vehicles Using Deep Reinforcement Learning

The climate-adaptive energy management system holds promising potential for harnessing the concealed energy-saving capabilities of connected plug-in hybrid electric vehicles. This research focuses on exploring the synergistic effects of artificial intelligence control and traffic preview to enhance the performance of the energy management system (EMS). A high-fidelity model of a multi-mode connected PHEV is calibrated using experimental data as a foundation. Subsequently, a model-free multistate deep reinforcement learning (DRL) algorithm is proposed to develop the integrated thermal and energy management (ITEM) system, incorporating features of engine smart warm-up and engine-assisted heating for cold climate conditions. The optimality and adaptability of the proposed system is evaluated through both offline tests and online hardware-in-the-loop tests, encompassing a homologation driving cycle and a real-world driving cycle in China with real-time traffic data. The results demonstrate that ITEM achieves a close to dynamic programming fuel economy performance with a margin of 93.7%, while reducing fuel consumption ranging from 2.2% to 9.6% as ambient temperature decreases from 15°C to -15°C in comparison to state-of-the-art DRL-based EMS solutions

Traffic-Aware Ecological Cruising Control for Connected Electric Vehicle

The advent of intelligent connected technology has greatly enriched the capabilities of vehicles in acquiring information. The integration of short-term information from limited sensing range and long-term information from cloud-based systems in vehicle motion planning and control has become a vital means to deeply explore the energy-saving potential of vehicles. In this study, a traffic-aware ecological cruising control (T-ECC) strategy based on a hierarchical framework for connected electric vehicles in uncertain traffic environments is proposed, leveraging the two distinct temporal-dimension information. In the upper layer that is dedicated for speed planning, a sustainable energy consumption strategy (SECS) is introduced for the first time. It finds the optimal economic speed by converting variations in kinetic energy into equivalent battery energy consumption based on long-term road information. In the lower layer, a synthetic rolling-horizon optimization control (SROC) is developed to handle real-time traffic uncertainties. This control approach jointly optimizes energy efficiency, battery life, driving safety, and comfort for vehicles under dynamically changing traffic conditions. Notably, a stochastic preceding vehicle model is presented to effectively capture the uncertainties in traffic during the driving process. Finally, the proposed T-ECC is validated through simulations in both virtual and real-world driving conditions. Results demonstrate that the proposed strategy significantly improves the energy efficiency of the vehicle

Protection against acute cerebral ischemia/reperfusion injury by QiShenYiQi via neuroinflammatory network mobilization

Cerebral ischemia/reperfusion injury (CI/RI) is a common feature of ischemic stroke, involving a period of impaired blood supply to the brain, followed by the restoration of cerebral perfusion through medical intervention. Although ischemia and reperfusion brain damage is a complex pathological process with an unclear physiological mechanism, more attention is currently focused on the neuroinflammatory response of an ischemia/reperfusion origin, and anti-inflammatory appears to be a potential therapeutic strategy following ischemic stroke. QiShenYiQi (QSYQ), a component-based Chinese medicine with Qi-tonifying and blood-activating property, has pharmacological actions of anti-inflammatory, antioxidant, mitochondrial protectant, anti-apoptosis, and antiplatelet aggregation. We have previously reported that the cardioprotective effect of QSYQ against ischemia/reperfusion injury is via improvement of mitochondrial functional integrity. In this research work, we aimed to investigate the possible mechanism involved in the neuroprotection of QSYQ in mice model of cerebral ischemia/reperfusion injury based on the inflammatory pathway. The cerebral protection was evaluated in the stroke mice after 24 h reperfusion by assessing the neurological deficit, cerebral infarction, brain edema, BBB functionality, and via histopathological assessment. TCM-based network pharmacology method was performed to establish and analyze compound-target-disease & function-pathway network so as to find the possible mechanism linking to the role of QSYQ in CI/RI. In addition, RT-qPCR was used to verify the accuracy of predicted signaling gene expression. As a result, improvement of neurological outcome, reduction of infarct volume and brain edema, a decrease in BBB disruption, and amelioration of histopathological alteration were observed in mice pretreated with QSYQ after experimental stroke surgery. Network pharmacology analysis revealed neuroinflammatory response was associated with the action of QSYQ in CI/RI. RT-qPCR data showed that the mice pretreated with QSYQ could significantly decrease IFNG-γ, IL-6, TNF-α, NF-κB p65, and TLR-4 mRNA levels and increase TGF-β1 mRNA level in the brain compared to the untreated mice after CI/RI (p \u3c 0.05). In conclusion, our study indicated the cerebral protective effect of pretreatment with QSYQ against CI/RI, which may be partly related to its potential to the reduction of neuroinflammatory response in a stroke subject

Galectin-3 Mediated Inflammatory Response Contributes to Neurological Recovery by QiShenYiQi in Subacute Stroke Model

Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke via modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly via regulating galectin-3 mediated inflammatory reaction

Qi-Shen-Yi-Qi Dripping Pills for the Secondary Prevention of Myocardial Infarction: A Randomised Clinical Trial

Background. Several types of drugs have been recommended for the secondary prevention of myocardial infarction (MI). However, these conventional strategies have several limitations, such as low adherence, high cost, and side effects during long time use. Novel approaches to this problem are still needed. This trial aimed to test the effectiveness and safety of Qi-Shen-Yi-Qi Dripping Pills (QSYQ), a multi-ingredient Chinese patent medicine, for the secondary prevention of MI. Methods and Findings. A total of 3505 eligible patients were randomly assigned to QSYQ group (1746 patients) or aspirin group (1759). Patients took their treatments for 12 months. The final follow-up visit took place 6 months after the end of the trial drugs. The 12-month and 18-month estimated incidences of the primary outcome were 2.98% and 3.67%, respectively, in the QSYQ group. The figures were 2.96% and 3.81% in the aspirin group. No significant difference was identified between the groups. Conclusions. This trial did not show significant difference of primary and secondary outcomes between aspirin and QSYQ in patients who have had an MI. Though inconclusive, the result suggests that QSYQ has similar effects to aspirin in the secondary prevention of MI

Comparative pharmacokinetic study of ascaridole after oral administration of ascaridole and Jinghuaweikang capsule to rats

The objective of this study was to compare the pharmacokinetic characteristics of ascaridole following oral administration of pure ascaridole and Jinghuaweikang (JHWK) capsule. Besides, additional rats were given pure ascaridole via intravenous administration for the bioavailability study. The concentration of ascaridole in rat plasma was determined by a GC/MS method. Following oral administration of pure ascaridole and JHWK capsule, the maximum mean concentration in rat plasma (Cmax, 2701.4 ± 1282.6 ng/mL and 3008.0 ± 273.5 ng/mL) were achieved at 0.25 ± 0.09 h and 0.47 ± 0.22 h (Tmax), and the absolute bioavailabilities were approximately 20.8 and 26.9 %, respectively. The results indicated that other ingredients in JHWK capsule might facilitate and prolong the absorption procedure of ascaridole, and thus enhance its bioavailability in rats. The present study provided the necessary information for the further investigation of Chenopodium ambrosioides L. and its preparation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Immunoregulation of Shenqi Fuzheng Injection Combined with Chemotherapy in Cancer Patients: A Systematic Review and Meta-Analysis

Background. Immunosuppression is a well-recognised complication of chemotherapy in cancer patients. We assemble the clinical evidence that SQI, an adjuvant drug for lung cancer and gastric cancer which was widely prescribed in China, interventions could increase objective tumour response and regulate immunity in cancer patients undergoing chemotherapy. Methods. We undertook a systemic review of the clinical data from randomised controlled trials up to September 2015 in which a SQI intervention was compared with a control arm in patients undergoing conventional chemotherapy. Revman 5.0 Software was used for the data analysis. Results. 49 randomised controlled trials were included in the systematic review. The meta-analysis results demonstrated that the SQI intervention with conventional chemotherapy exhibited better therapeutic efficacy than the conventional chemotherapy group with a statistically significant higher objective tumour response. Cotreatment with SQI could enhance NK, CD3+, CD4+ level, and CD4+/CD8+ ratio comparing with the conventional chemotherapy group. Conclusions. The conclusions of this review might suggest a high risk of bias due to the low quality and the limitation of cancer types in the included trials. A more reliable conclusion regarding the immunoregulation of SQI could be reached based on more trials of higher quality

Qishen Yiqi dripping pills for chronic ischaemic heart failure:results of the CACT-IHF randomized clinical trial

10.1002/ehf2.12980ESC Heart Failure763881-389

Endogenous SIRT6 in platelets negatively regulates platelet activation and thrombosis

Thromboembolism resulting from platelet dysfunction constitutes a significant contributor to the development of cardiovascular disease. Sirtuin 6 (SIRT6), an essential NAD+-dependent enzyme, has been linked to arterial thrombosis when absent in endothelial cells. In the present study, we have confirmed the presence of SIRT6 protein in anucleated platelets. However, the precise regulatory role of platelet endogenous SIRT6 in platelet activation and thrombotic processes has remained uncertain. Herein, we present compelling evidence demonstrating that platelets isolated from SIRT6-knockout mice (SIRT6−/−) exhibit a notable augmentation in thrombin-induced platelet activation, aggregation, and clot retraction. In contrast, activation of SIRT6 through specific agonist treatment (UBCS039) confers a pronounced protective effect on platelet activation and arterial thrombosis. Moreover, in platelet adoptive transfer experiments between wild-type (WT) and SIRT6−/− mice, the loss of SIRT6 in platelets significantly prolongs the mean thrombus occlusion time in a FeCl3-induced arterial thrombosis mouse model. Mechanistically, we have identified that SIRT6 deficiency in platelets leads to the enhanced expression and release of proprotein convertase subtilisin/kexin type 9 (PCSK9), subsequently activating the platelet activation-associated mitogen-activated protein kinase (MAPK) signaling pathway. These findings collectively unveil a novel protective role of platelet endogenous SIRT6 in platelet activation and thrombosis. This protective effect is, at least in part, attributed to the inhibition of platelet PCSK9 secretion and mitogen-activated protein kinase signaling transduction. Our study provides valuable insights into the intricate interplay between SIRT6 and platelet function, shedding light on potential therapeutic avenues for managing thrombotic disorders