ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

OBJECTIVES: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). METHODS: Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. RESULTS: HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. CONCLUSIONS NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism* ; Animals ; Hepatocytes/metabolism* ; Lipid Metabolism ; Mice ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; AMP-Activated Protein Kinases/metabolism* ; Carnitine O-Palmitoyltransferase/metabolism* ; Diet, High-Fat ; Male ; Mice, Inbred C57BL ; Signal Transduction

Objective To explore the differences in neck and lumbar spine injuries among different types of aircraft pilots and the correlation between body surface temperature and the severity of injury.Methods Data were collected by questionnaire surveys and medical examinations.Forty male pilots were selected as research objects,including 14 fighter pilots and 26 helicopter pilots,aged between 28 and 39 years,with a height range of 168 to 178 cm,and a total flight time of 600 to 2 000 h.Infrared thermal imaging was employed for skin temperature.A questionnaire survey was conducted for the assessment of the common site and degree of pain.The relationship between body surface temperature and pain was investigated.Results Fighter pilots mainly complained of discomfort in the neck and scapular region,while helicopter pilots were more likely to experience lower back pain.The skin temperature in the affected regions was significantly higher than that in the surrounding normal regions in both fighter pilots and helicopter pilots(P<0.05).The pain score was positively related with elevated temperature in the affected areas(P<0.05).Conclusion It is found that fighter pilots are more prone to neck and scapular pain,while helicopter pilots are more likely to experience lower back pain.The severity of pain is positively related with increased temperature in the affected areas.Infrared thermal imaging can be used to assess temperature variation at injured sites and the location of training injuries among pilots.

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg^-1·d^-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P＜0.05),while the level of IL-10 was significantly decreased(P＜0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P＜0.05)and IL-10 was sig-nificantly increased(P＜0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P＜0.05)and increased the levels of growth hormone(GH)(P＜0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P＜0.05)and up-regula-ted that of STAT3(P＜0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.

Objective To assess the predictive value of the model combined conventional metabolic parameters and radiomics fea-tures from 18F-FDG PET/CT for predicting HER-2 expression status in gastric cancer.Methods A retrospective analysis included 110 gastric cancer patients from The Second Hospital Lanzhou University and The Gansu Provincial People's Hospital.All patients under-went 18 F-FDG PET/CT before treatment.The Lanzhou cases were randomly divided into a 7∶3 training set(n=61)and an internal vali-dation set(n=26),while data from Gansu Provincial People's Hospital(n=23)served as an external validation set.LASSO regression and 10-fold cross-validation were employed to select PET parameters and radiomics features in the training set.Logistic regression was used to create PET,radiomics,and combined model.Evaluation included ROC curves and the DeLong test for model comparison.Clinical utility was assessed using decision curve analysis,and model consistency was observed through calibration curves.Results Models based on 3,2 and 5 selected features for the PET,radiomics,and combined model.ROC curves demonstrated strong predictive performance for all models.The DeLong test showed a significant difference between the combined model and radiomics model in the training set(P＜0.05),with no statistical difference between the PET model and radiomics model(P＞0.05).Internal and external validation sets showed no statistical differences among the three models(P＞0.05).Calibration curves indicated good fitting effects for each model,and decision curve analysis revealed higher clinical utility for the combined model compared to the other two models.Conclusion The combined model provides a robust predictive tool for determining HER-2 expression status in gastric cancer patients.