Objective:To document the effectiveness of ultrasound-guided genicular nerve block (GNB) in treating knee osteoarthritis (KOA).Methods:A total of 92 KOA patients were randomly divided into an observation group and a control group with 46 in each. Those in both groups were treated conventionally, including with non-steroidal anti-inflammatory drugs, acupuncture, ultrasound, laser irradiation and manipulation therapy. The observation group additionally underwent ultrasound-guided genicular nerve block treatment, once a week for 2 weeks. Pain scoring on a visual analog scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and a 6-minute walk test (6MWT) were used to evaluate everyone before and after the treatment, and then 8 weeks later.Results:In the observation group the average VAS rating [(3.54±2.00) at week 2 and (4.13±2.04) at week 8] and the average WOMAC subscale and total scores [(36.91±16.91) at week 8] had improved significantly right after the experiment and 8 weeks later. But in the control group this was true only right after the treatment. The observation group also demonstrated superior improvements in 6MWT distance at week 2 [(434.22±125.19)m] and week 8 [(446.35±126.45)m] compared to both its own baseline and the control group.Conclusions:Ultrasound-guided genicular nerve block is a rapid, precise, effective, and long-lasting intervention for alleviating pain, improving knee function and enhancing walking endurance in KOA patients.

OBJECTIVE To explore the APOA5 gene polymorphisms,serum lipase(LPS),soluble programmed death ligand 1(sPD-L1)and procalcitonin(PCT)in the severe acute pancreatitis(SAP)patients with secondary infectious pancreatic necrosis(IPN).METHODS A total of 122 patients with SAP who were treated in the First Affiliated Hospital of Hebei North University from Jan.2020 to Nov.2023 were recruited as the research subjects and were divided into the secondary group with 31 cases and the non-secondary group with 91 cases according to the status of secondary IPN.The APOA5 gene polymorphisms were detected for the two groups of patients by means of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The levels of LPS,sPD-L1 and PCT as well as Ranson score were compared between he two groups.The association of the serum LPS,sPD-L1 and PCT with Ranson score was observed by Spearman analysis.The value of the joint detection of LPS,sPD-L1 and PCT in diagnosis of secondary IPN in the SAP patients was analyzed by means of receiver oper-ating characteristic(ROC)curves.RESULTS The frequencies of AA genotype and A allele at rs619054 locus of APOA5 gene were higher in the secondary group than in the non-secondary group(P＜0.05),and the frequency of G allele of the secondary group was lower than that of the non-secondary group(P＜0.05).There were significant differences in the levels of serum LPS,sPD-L1 and PCT as well as Ranson score between the secondary group and the non-secondary group(P＜0.05).Spearman analysis showed that the Ranson score was positively correlated with the levels of serum LPS,sPD-L1 and PCT(r=0.738,0.701,0.721,P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of the joint detection of the three indexes was higher than that of the single detection in diagnosis of secondary IPN in the SAP patients(P＜0.05),with the sensitivity 90.30％,the specifici-ty 84.60％.CONCLUSIONS The SAP patients with secondary IPN show the high expressions of LPS,sPD-L1 and PCT.The joint detection of the indexes may facilitate the diagnosis of the secondary IPN in the SAP patients.There is association between the levels of LPS,sPD-L1 and PCT and the Ranson score.The rs619054 locus of APOA5 gene may be involved in pathogenesis of secondary IPN in the SAP patients.

OBJECTIVE To explore the APOA5 gene polymorphisms,serum lipase(LPS),soluble programmed death ligand 1(sPD-L1)and procalcitonin(PCT)in the severe acute pancreatitis(SAP)patients with secondary infectious pancreatic necrosis(IPN).METHODS A total of 122 patients with SAP who were treated in the First Affiliated Hospital of Hebei North University from Jan.2020 to Nov.2023 were recruited as the research subjects and were divided into the secondary group with 31 cases and the non-secondary group with 91 cases according to the status of secondary IPN.The APOA5 gene polymorphisms were detected for the two groups of patients by means of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The levels of LPS,sPD-L1 and PCT as well as Ranson score were compared between he two groups.The association of the serum LPS,sPD-L1 and PCT with Ranson score was observed by Spearman analysis.The value of the joint detection of LPS,sPD-L1 and PCT in diagnosis of secondary IPN in the SAP patients was analyzed by means of receiver oper-ating characteristic(ROC)curves.RESULTS The frequencies of AA genotype and A allele at rs619054 locus of APOA5 gene were higher in the secondary group than in the non-secondary group(P＜0.05),and the frequency of G allele of the secondary group was lower than that of the non-secondary group(P＜0.05).There were significant differences in the levels of serum LPS,sPD-L1 and PCT as well as Ranson score between the secondary group and the non-secondary group(P＜0.05).Spearman analysis showed that the Ranson score was positively correlated with the levels of serum LPS,sPD-L1 and PCT(r=0.738,0.701,0.721,P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of the joint detection of the three indexes was higher than that of the single detection in diagnosis of secondary IPN in the SAP patients(P＜0.05),with the sensitivity 90.30％,the specifici-ty 84.60％.CONCLUSIONS The SAP patients with secondary IPN show the high expressions of LPS,sPD-L1 and PCT.The joint detection of the indexes may facilitate the diagnosis of the secondary IPN in the SAP patients.There is association between the levels of LPS,sPD-L1 and PCT and the Ranson score.The rs619054 locus of APOA5 gene may be involved in pathogenesis of secondary IPN in the SAP patients.

Objective:To document the effectiveness of ultrasound-guided genicular nerve block (GNB) in treating knee osteoarthritis (KOA).Methods:A total of 92 KOA patients were randomly divided into an observation group and a control group with 46 in each. Those in both groups were treated conventionally, including with non-steroidal anti-inflammatory drugs, acupuncture, ultrasound, laser irradiation and manipulation therapy. The observation group additionally underwent ultrasound-guided genicular nerve block treatment, once a week for 2 weeks. Pain scoring on a visual analog scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and a 6-minute walk test (6MWT) were used to evaluate everyone before and after the treatment, and then 8 weeks later.Results:In the observation group the average VAS rating [(3.54±2.00) at week 2 and (4.13±2.04) at week 8] and the average WOMAC subscale and total scores [(36.91±16.91) at week 8] had improved significantly right after the experiment and 8 weeks later. But in the control group this was true only right after the treatment. The observation group also demonstrated superior improvements in 6MWT distance at week 2 [(434.22±125.19)m] and week 8 [(446.35±126.45)m] compared to both its own baseline and the control group.Conclusions:Ultrasound-guided genicular nerve block is a rapid, precise, effective, and long-lasting intervention for alleviating pain, improving knee function and enhancing walking endurance in KOA patients.

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.

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.

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.

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.

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.