Calycosin attenuates severe acute pancreatitis-associated acute lung injury by curtailing high mobility group box 1-induced inflammation

BACKGROUND Acute lung injury(ALI)is a common and life-threatening complication of severe acute pancreatitis(SAP).There are currently limited effective treatment options for SAP and associated ALI.Calycosin(Cal),a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties,but its effect on SAP and associated ALI has yet to be determined.AIM To identify the roles of Cal in SAP-ALI and the underlying mechanism.METHODS SAP was induced via two intraperitoneal injections of L-arg(4 g/kg)and Cal(25 or 50 mg/kg)were injected 1 h prior to the first L-arg challenge.Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically.An in vitro model of lipopolysaccharide(LPS)-induced ALI was established using A549 cells.Immunofluorescence analysis and western blot were evaluated in cells.Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.RESULTS Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI.Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP.Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α,interleukin-6,IL-1β,HMGB1 and chemokine(CXC motif)ligand 1 in lung tissue.Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B(NF-κB)p65 in lung tissues and an in vitro model of LPSinduced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI.Furthermore,molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.CONCLUSION Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.

Gene knockout or inhibition of macrophage migration inhibitory factor alleviates lipopolysaccharide-induced liver injury via inhibiting inflammatory response

Background:Liver injury is one of the most common complications during sepsis.Macrophage migration inhibitory factor(MIF)is an important proinflammatory cytokine.This study explored the role of MIF in the lipopolysaccharide(LPS)-induced liver injury through genetically manipulated mouse strains.Methods:The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil)were detected,and the expressions of MIF,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured.Liver histopathology was conducted to assess liver injury.Moreover,the inhibitions of MIF with(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)and 4-iodo-6-phenylpyrimidine(4-IPP)were used to evaluate their therapeutic potential of liver injury.Results:Compared with wild-type mice,the liver function indices and inflammation factors presented no significant difference in the Mif-/-mice.After 72 h of the LPS-induced liver injury,serum levels of ALT,AST,and TBil as well as TNF-αand IL-1βwere significantly increased,but the knockout of Mif attenuated liver injury and inflammatory response.In liver tissue,m RNA levels of TNF-α,IL-1βand NF-κB p65 were remarkably elevated in LPS-induced liver injury,while the knockout of Mif reduced these levels.Moreover,in LPS-induced liver injury,the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response.Importantly,compared to mice with LPS-induced liver injury,Mif knockout or MIF inhibitions significantly prolonged the survival of the mice.Conclusions:In LPS-induced liver injury,the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response,thereby prolonged the survival of the mice.Targeting MIF may be an important strategy to protect the liver from injury during sepsis.

Fixation of Calcaneal Tuberosity Beavis II Fracture in Elderly Patients Using Locking Plate Combined with Tension Screw

Background:Calcaneus is the largest bone of foot and the main load-bearing structure of heel.The incidence of simple calcaneal tubercle avulsion fracture is low,accounting for about 1%to 3%of all calcaneal fractures.Beavis II fracture has large bone fracture,obvious displacement,obvious soft tissue irritation,and often leads to skin necrosis.It needs surgical treatment,reduction and fixation as soon as possible.Although open reduction and tension screw internal fixation is used for Beavis II calcaneal tubercle fracture,but the failure rate is more common.Methods:This study retrospectively analyzed the surgical treatment of calcaneal tubercle Beavis II fracture over 55 years old in our hospital from January 2013 to January 2019.The patients were treated with tension screw combined with locking plate,and followed up and analyzed.Results:12 patients in this group were followed up for 12 to 36 months(mean 20 months).After operation,the fracture healed smoothly in all patients,the healing time was 8 to 12 weeks(mean 10.7 weeks),and there were no complications such as poor incision healing,fracture displacement,internal fixation loosening,fracture and so on.When the patients were followed up 18 weeks after operation,the AOFAS score was 47 to 100,with an average of 91.1,of which 8 cases were excellent,3 good and 1 poor,with an excellent and good rate of 91.7%.Conclusion:Our hospital has been treated with tension screw combined with locking plate,fixed firmly,can early functional exercise,achieved good results.

Accelerating Data Transfer in Dataflow Architectures Through a Look-Ahead Acknowledgment Mechanism

The dataflow architecture,which is characterized by a lack of a redundant unified control logic,has been shown to have an advantage over the control-flow architecture as it improves the computational performance and power efficiency,especially of applications used in high-performance computing(HPC).Importantly,the high computational efficiency of systems using the dataflow architecture is achieved by allowing program kernels to be activated in a simultaneous manner.Therefore,a proper acknowledgment mechanism is required to distinguish the data that logically belongs to different contexts.Possible solutions include the tagged-token matching mechanism in which the data is sent before acknowledgments are received but retried after rejection,or a handshake mechanism in which the data is only sent after acknowledgments are received.However,these mechanisms are characterized by both inefficient data transfer and increased area cost.Good performance of the dataflow architecture depends on the efficiency of data transfer.In order to optimize the efficiency of data transfer in existing dataflow architectures with a minimal increase in area and power cost,we propose a Look-Ahead Acknowledgment(LAA)mechanism.LAA accelerates the execution flow by speculatively acknowledging ahead without penalties.Our simulation analysis based on a handshake mechanism shows that our LAA increases the average utilization of computational units by 23.9%,with a reduction in the average execution time by 17.4%and an increase in the average power efficiency of dataflow processors by 22.4%.Crucially,our novel approach results in a relatively small increase in the area and power consumption of the on-chip logic of less than 0.9%.In conclusion,the evaluation results suggest that Look-Ahead Acknowledgment is an effective improvement for data transfer in existing dataflow architectures.