Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

ObjectiveTo investigate the mechanisms of Panax notoginseng saponins （PNS） in inhibiting high shear-induced platelet aggregation and thrombosis via the Piezo1-mediated calcium signaling pathway. MethodBioflux1000z was used for the microfluidic assay， where platelets were stimulated with physiological shear rate （500 s^-1）， pathological shear rate （12 000 s^-1）， or Piezo1 agonist Yoda1 under the physiological shear rate （500 s^-1）. The shear-induced platelet calcium influx and the binding of platelet with von Willebrand factor （vWF） were measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the vWF release from platelets. The microfluidic channels were used to determine the vWF-mediated platelet aggregation and integrin αⅡbβ3 activation. A mouse model of arterial thrombosis induced by high shear stress combined with endothelial injury was established. The ultrasonic Doppler flow meter was used to monitor the cyclic flow reduction （CFR） caused by the repeated formation and shedding of thrombi， and flow cytometry was employed to examine platelet-vWF binding， on the basis of which the effect of PNS on high shear-induced arterial thrombosis was evaluated. ResultThe microfluidic assay showed that PNS decreased the high shear rate （12 000 s^-1） or Yoda1-induced calcium influx， platelet-vWF binding， vWF-mediated platelet-fibrinogen binding， and vWF release from platelet alpha-granules in a dose-dependent manner. In the mouse model of high shear-induced thrombosis， PNS markedly reduced the CFR and occlusion time of the common carotid artery and inhibited platelet-vWF binding. ConclusionPNS can mitigate pathological shear-induced platelet aggregation and arterial thrombosis via influencing Piezo1/GPIbα-vWF signaling.

Purpose/Significance The load balancing scheduling method is proposed to shorten the waiting time and balance the load of each machine in additive manufacturing of customized medical devices.Method/Process By analyzing the influencing factors in the time dimension,the mathematical model of the two-objective multi-constraint optimization problem is established.The load balancing operator is introduced and the load balancing scheduling algorithm is used to solve the model.Result/Conclusion The load balancing scheduling method with load balancing operators is superior to other algorithms in terms of task waiting time and load balancing perform-ance,especially for large-scale tasks.This method can effectively shorten task waiting time and realize machine load balancing.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Objective In this study,we aimed to use network pharmacology techniques to predict the key targets of a prescription of Ziziphi spinosae semen formula(ZSSF)compound for depression,and to verify its mechanism of action using a zebrafish model of rifampicin-induced depression.Methods The drug targets of ZSSF were retrieved from the TCMSP database,and the target names were corrected using the UniProt database.Depression-related targets were identified using the GeneCards,OMIM,and NCBI databases.Protein-protein interaction information for the shared targets was predicted using the STRING database.The collected data were then analyzed using the Metascape database to determine GO and KEGG pathway enrichment,and the result were visualized using microbiotics.Behavioral experiments and reverse-transcription quantitative PCR experiments were conducted to verify the therapeutic effects of ZSSF on a zebrafish depression model induced by risperdal.Results 188 targets were screened to find the interactions between depression and ZSSF.The protein-protein interaction result showed that ZSSF primarily targeted TNF-α,IL-2,IL-6,IL-1β,and IL-10 to produce its antidepressant effect.KEGG pathway enrichment analysis revealed that ZSSF exerted its effects on depression through various signaling pathways,including the TNF,PI3K-Akt,and cGMP-PKG signaling pathways.The result of the animal experiments showed that the treatment groups given high,medium,and low doses of ZSSF exhibited significant improvements in movement distance under acoustic and light stimulation compared with the model group(P＜0.05).The speed of movement of the treatment groups was also significantly faster(P＜0.01).Additionally,the mRNA expression levels of TNF-α,IL-2,IL-6,IL-1β,and IL-10 were up-regulated in the brain tissues of zebrafish in the high-,medium-,and low-dosage groups of ZSSF compared those in the model group(P＜0.001).Conclusions ZSSF exerts its antidepressant effect through multiple components and targets,and its antidepressant effects may be associated with its inhibition of inflammatory factors.

Ischemic stroke is one of the leading causes of death and disability worldwide. In Han dynasty， HUA Tuo proposed the original preventive medicine idea that "with good blood circulation， the disease cannot be born"， which opened a broad space for the cross-research of blood-related mechanical factors and pharmacology. In the pathogenesis of ischemic stroke， mechanical factors comprehensively affect the function and crosstalk of platelets and endothelial cells. In recent years， as the well-known effects on thrombosis and stroke， more attention has been paid to hemodynamic factors as the participants involved in pathological mechanisms and potential therapeutic targets of ischemic stroke. The mechanical force ion channel Piezo1 widely exists on the surface of many types of cells. Besides being regulated by chemical and endogenous substances， Piezo1 responds to different mechanical conditions， regulates the opening and closing of channels， and activates different downstream signaling pathways. Piezo1 is now regarded as an important connection between mechanical and biochemical signals. A variety of Chinese medicine can affect the activity of Piezo1 protein， which may prevent and treat thrombotic diseases such as ischemic stroke through Piezo1 protein. In this paper， the effects of Piezo1 protein on the physiological and pathological functions of endothelial cells and platelet under different mechanical conditions and the role of Piezo1 in the process of thrombosis were reviewed， as well as the effects of Chinese medicine， chemical medicine， and endogenous substances targeting Piezo1 channel. These could provide new ideas for further exploring the mechanisms of Chinese medicines in activating blood circulation， developing new drugs， and deepening biomechanical-pharmacology research.

Objective:To evaluate the value of bedside ultrasound in evaluating volume responsiveness of patients with septic shock.Methods:A total of 102 patients with septic shock admitted to ICU of the First Affiliated Hospital of Hebei North University from April 2018 to February 2021 were selected. Patients were divided into response group and non-response group according to the value of stroke volume increase (ΔSV) after volume loading test (VE), and the hemodynamic parameters before and after VE were compared between the two groups. Pearson correlation was used to analyze the relationship between ΔSV and hemodynamic indexes. Receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of each hemodynamic index in evaluating volumetric reactivity in patients with septic shock.Results:Of the 102 patients, 54 responded and 48 did not. Before VE, the distensibility index of inferior vena cava (ΔIVC 1), espiratory variability index of inferior vena cava (ΔIVC 2), respiratory variability of aortic peak velocity (ΔVpeak AO), brachial artery maximum velocity variability (ΔVpeak BA) and respiratory rate of peak flow velocity of femoral artery (ΔVpeak CFA) in response group were higher than those in non-response group (all P<0.05), but there was no statistical significance in heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) between 2 groups (all P>0.05). After VE, the HR, ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA in response group were significantly decreased, while MAP and CVP were significantly increased (all P<0.05). The CVP was significantly decreased in the non-response group ( P<0.05), while other indexes were not significantly changed. Before VE, the ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA were positively correlated with ΔSV ( r=0.589, 0.647, 0.697, 0.621, 0.766; all P<0.05). There was no correlation between CVP and ΔSV ( r=-0.345, P>0.05). Before VE, the area under the curve of ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA were all >0.7, indicating high sensitivity and specificity. Conclusions:Bedside ultrasound monitoring ΔIVC, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA can better evaluate the volume response of patients with septic shock, and can provide a reference basis for clinical fluid resuscitation treatment.

Objective : To explore the method of intraperitoneal injection of allogenic fecal filtrate to establish the rat model of moderate and severe sepsis． Methods: The preparation method of allogeneic fecal filtrate was determined．Allogeneic fecal filtrate of different concentrations (0. 5，1，2 g / kg) was injected intraperitoneally to observe the general situation，survival time and severe degree of sepsis of rats. After determining the optimal concentration，the success rate of the model，serum inflammatory factors，serum concentration of D-lactic acid ( D-LA) and serum intestinal fatty acid binding protein (I-FABP) ，lung function changes，lung，liver and kidney tissue injury were further observed. Results: After intraperitoneal injection of allogenic fecal filtrate for 24 h，the rats of 1 g / kg group presented fever，tachypnea and hypotension，the survival rate was 83. 3% at 24 h and 16. 7% at 48 h， 2 g / kg group rats all died within 24 h，the dose of 1 g / kg was determined for subsequent experiments．Injected fecal filtrate for 24 h，the success rate of the sepsis model was 77. 8% . The levels of interleukin-6 ( IL-6) ，tumor necrosis factor-α ( TNF-α) ，D-LA and I-FABP in serum significantly increased． There were severe edema and bleeding in lung tissue，Pulmonary function appeared respiratory dysfunction，included functional residual capacity (FRC) ，quasi static compliance ( Cdyn) ，forced expiratory volume for the first 100 milliseconds(FEV100) ，peak expiratory flow (PEF) decreased，airway resistance (RI) ，inspiratory capacity (IC) increased．Liver and kidney tissues also showed varying degrees of edema and inflammatory cell infiltration，the levels of alanine aminotransferase (ALT) ，aspartate aminotransferase (AST) ，blood urea nitrogen (BUN) and creatinine ( Cr) in serum significantly increased． Conclusion Intraperitoneal injection of allogenic fecal filtrate ( 1 g / kg) can produce a relative typical septic model in rats.

Cartilage surface fibrosis is an early sign of osteoarthritis and cartilage surface damage is closely related to load. The purpose of this study was to study the relationship between cartilage surface roughness and load. By applying impact, compression and fatigue loads on fresh porcine articular cartilage, the rough value of cartilage surface was measured at an interval of 10 min each time and the change rule of roughness before and after loading was obtained. It was found that the load increased the roughness of cartilage surface and the increased value was related to the load size. The time of roughness returning to the initial condition was related to the load type and the load size. The impact load had the greatest influence on the roughness of cartilage surface, followed by the severe fatigue load, compression load and mild fatigue load. This article provides reference data for revealing the pathogenesis of early osteoarthritis and preventing and treating articular cartilage diseases.
Animals ; Cartilage, Articular ; Fatigue ; Osteoarthritis/pathology* ; Pressure ; Swine