ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

Indocyanine green(ICG)is one of the near-infrared fluorescent contrast agents approved for clinical use in fluorescence-guided surgery.Although widely applied,it still has some limitations.In recent years,various targeted fluorescent agents have been explored in pancreatic cancer patients;however,there is still no standardized consensus among surgeons regarding fluorescence-guided surgery for pancreatic cancer.In 2023,the first the international consensus report on fluorescent surgery navigation for pancreatic tumors was published,gathering perspectives from 38 pancreatic surgeons worldwide on current practices and future directions.A total of 76 statements were anonymously voted on using the Delphi method,resulting in 61 recommended statements.This consensus offers valuable guidance for the implementation of fluorescence-guided surgery in pancreatic tumor operations in China,yet its clinical application should be adapted in consideration of local expert opinions and patient-specific factors.This article interprets key aspects of the consensus,including the use of ICG,intraoperative fluorescence imaging techniques,and the fluorescence heterogeneity of pancreatic tumors,in combination with the authors'clinical experience,with the aim of providing reference and insight for the application of fluorescence-guided surgery in pancreatic tumors.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.

To comprehend the genetic evolutionary characteristics and biological properties of the H4N1 subtype avian influenza virus(AIV)in China,this study conducted whole genome sequen-cing,genetic evolutionary analysis,and pathogenicity test in BALB/c mice of a duck-derived H4N1 subtype AIV strain(DK/GX/E1424/20)isolated from the live poultry market in the southern re-gion in 2020.The results indicated that the cleavage site motif of the HA protein was PEKASR/GLF,which conformed to the characteristics of low pathogenic AIV.All the eight gene fragments were situated in the Eurasian lineage,and the homology of AIV-related genes of the H1N1,H3N8,H4N6,H6N1,and H10N8 subtypes isolated from wild waterfowl was the highest,representing a recombinant virus strain.Without prior adaptation,it replicated effectively in the lungs and turbi-nates of mice,with viral titers of 3.00 and 2.08 log10EID50/mL respectively,and induced weight loss in infected mice.This study suggested that this virus had significant genetic diversity and low pathogenicity in mice,posing a potential risk for mammalian infection.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.