Objective To investigate the protective effects of the ANXA1(Annexin A1)mimetic peptide Ac2-26 on mice with severe heatstroke(HS)and its underlying mechanisms.Methods Twenty-four adult healthy male C57BL/6J mice weighing 20-25 g were randomly divided into four groups using a simple random sampling method:control group(Con group),Con+Ac2-26 group,severe heatstroke group(HS group),and severe heatstroke+Ac2-26 group(HS+Ac2-26 group),with 6 mice in each group.Mice in Con+Ac2-26 group and HS+Ac2-26 group were injected intraperitoneally with Ac2-26(6 mg/kg),and the remaining mice of two groups were injected intraperitoneally with normal saline of equivalent volume.One hour after drug administration,mice in HS group and HS+Ac2-26 group were placed in a high-temperature and high-humidity simulated environment[(37.0±0.5)℃,75%±5%humidity],while mice in Con group and Con+Ac2-26 were kept in a room temperature and humidity environment[(24±0.5)℃and 40±5%humidity]throughout the experiment.The anal temperature of the mice was recorded every 5 minutes;when the anal temperature of mice in HS group and HS+Ac2-26 group reached 42℃,they were removed from the high-temperature environment and placed in a room temperature environment for 6 hours of rewarming,after which blood samples of mice in each group were collected.Flow cytometry was used to detect the proportion of neutrophils and the expression levels of Cd11b and Cd62L(molecules related to neutrophil activation).Enzyme-linked immunosorbent assay(ELISA)was used to measure the plasma levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),IL-10,and IL-4.Hematoxylin-eosin staining(HE staining)was performed to observe the pathological changes in lung,kidney and liver tissues.Furthermore,RNA sequencing(RNA-seq)was conducted to detect changes in neutrophil gene expression.Results Compared with Con group,Con+Ac2-26 group showed no significant increase in neutrophil proportion,decreased expression of CD62L and CD11b,no significant changes in cytokine levels,and no obvious pathological changes in lung,kidney,or liver tissues.Compared with HS group,the time for mice in HS+Ac2-26 group to reach an anal temperature of 42℃and the time to develop hypothermia after model establishment were both prolonged(P<0.05);the proportion of neutrophils was reduced(P<0.05);the plasma levels of pro-inflammatory cytokines TNF-α and IL-6 were decreased(P<0.05);and the plasma level of anti-inflammatory cytokine IL-10 was increased(P<0.05).HE staining results showed that compared with HS group,HS+Ac2-26 group had a reduced range of inflammatory cell infiltration in lung,kidney,and liver tissues.RNA-seq results revealed that compared with HS group,HS+Ac2-26 group had decreased expression levels of molecules related to the oxidative phosphorylation signaling pathways and neutrophil extracellular trap(NETs).Conclusion Annexin A1 mimetic peptide Ac2-26 may reduce the pro-inflammatory response and alleviate the heatstroke-induced organ histopathologic damage in heatstroke mice by inhibiting oxidative phosphorylation in heat-stressed cells and NETs formation.

Objective:To construct a prognostic risk prediction model for colorectal cancer(CRC)based on endoplasmic reticulum stress(ERS)-related genes,and to evaluate the value of the model in predicting the prognosis of CRC.Methods:The gene data and clinical information of CRC group were downloaded from the TCGA database,and a prognostic risk prediction model based on ERS-related genes was designed by LASSO regression and multivariate Cox regression analysis.The model was used to predict the prognostic risk and immune response of CRC pa-tients,and the ROC curve was used to evaluate the efficacy of the risk prediction model.Re-sults:A total of 255 ERS-related genes were found in the data of 455 CRC cases,and 11 prognosis-related genes,including HSPA1A,MAGEA3,ATP2A1,DNAJB2,DNAJC3,EIF2B5,FLOT1,GET4,HERPUD2,STC2 and TMUB1,were screened by multivariate Cox regression,and a prognostic risk prediction model was constructed,with risk score=0.151 × HSPA1A+0.240 × MAGEA3+1.715 × ATP2A1+1.162 × DNAJB2-0.563 × DNAJC3+1.127 × EIF2B5+0.653 × FLOT1-1.580 × GET4+1.684 × HERPUD2+0.260 × STC2+0.710 × TMUB1.Higher risk scores were associ-ated with worse prognosis,immune response,drug sensitivity in patients and the lower the TMB score.Compared to traditional TNM staging,the area under the ROC curve(AUC=0.78)and C in-dex of the prognostic risk prediction model were higher.Conclusion:The prognostic risk predic-tion model of ERS-related genes has a good predictive effect on the prognosis of CRCand pro-vides guidance for the application of immunotherapy.

Osteoporosis is an important cause of internal fixation loosening after spinal surgery.Cement-augmented pedicle screw instru-mentation(CAPSI)technique is the most widely used technique in clinical practice to improve the stability of pedicle screw,mainly applied in osteoporosis and revision surgery,which included conventional solid pedicles crews and fenestrated/cannulated pedicle screws technique.CAPSI technique may cause cement leakage and pulmonary embolism,and there is no consensus on its indications or technical points.Therefore,this article reviews the research progress of CAPSI,in order to provide relevant reference for clinical practice.

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.
Humans ; Aged ; Wound Healing/physiology* ; Adipocytes ; Adipose Tissue ; Extracellular Matrix ; Stem Cells

This study aims to explore the neuroprotective effect of bilobalide(BB) and the mechanisms such as inhibiting inflammatory response in macrophage/microglia, promoting neurotrophic factor secretion, and interfering with the activation and differentiation of peripheral CD4~+ T cells. BB of different concentration(12.5, 25, 50, 100 μg·mL~(-1)) was used to treat the RAW264.7 and BV2 cells for 24 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and cell counting kit-8(CCK-8) were employed to detect the cytotoxicity of BB and appropriate concentration was selected for further experiment. Lipopolysaccharide(LPS) was applied to elicit inflammation in RAW264.7 and BV2 cells, mouse bone marrow-derived macrophages(BMDMs), and primary microglia, respectively. The effect of BB on cell proliferation and secretion of inflammatory cytokines and neurotrophic factors was detected by enzyme-linked immunosorbent assay(ELISA). Spleen monocytes of C57BL/6 female mice(7-8 weeks old) were isolated, and CD4~+ T cells were separated by magnetic beads under sterile conditions. Th17 cells were induced by CD3/CD28 and the conditioned medium for eliciting the inflammation in BMDMs. The content of IL-17 cytokines in the supernatant was detected by ELISA to determine the effect on the activation and differentiation of CD4~+ T cells. In addition, PC12 cells were incubated with the conditioned medium for eliciting inflammation in BMDMs and primary microglia and the count and morphology of cells were observed. The cytoto-xicity was determined by lactate dehydrogenase(LDH) assay. The result showed that BB with the concentration of 12.5-100 μg·mL~(-1) had no toxicity to RAW264.7 and BV2 cells, and had no significant effect on the activity of cell model with low inflammation. The 50 μg·mL~(-1) BB was selected for further experiment, and the results indicated that BB inhibited LPS-induced secretion of inflammatory cytokines. The experiment on CD4~+ T cells showed that the conditioned medium for LPS-induced inflammation in BMDMs promoted the activation and differentiation of CD4~+ T cells, while the conditioned medium of the experimental group with BB intervention reduced the activation and differentiation of CD4~+ T cells. In addition, BB also enhanced the release of neurotrophic factors from BMDMs and primary microglia. The conditioned medium after BB intervention can significantly reduce the death of PC12 neurons, inhibit neuronal damage, and protect neurons. To sum up, BB plays a neuroprotective role by inhibiting macrophage and microglia-mediated inflammatory response and promoting neurotrophic factors.
Female ; Rats ; Mice ; Animals ; Bilobalides/pharmacology* ; Neuroprotection ; Lipopolysaccharides/toxicity* ; Culture Media, Conditioned/pharmacology* ; Mice, Inbred C57BL ; Macrophages/metabolism* ; Microglia ; Cytokines/metabolism* ; Nerve Growth Factors/pharmacology* ; Inflammation/metabolism*

Aim To explore the protective effect of proanthocyanidin B2 (PC-B2) on oxidative damage of PC 12 cells induced by hydrogen peroxide (H

Aim To explore the mechanism of grape seed proanthocyanidins (GSPs) targeting astrocytes (AS), so as to regulate the phenotype and function of AS and maximize their neuroprotective effect. Methods The effects of GSPs on the phenotype, secretion of pro-inflammatory factors and neurotrophic factors of Al AS induced by TNF-α, IL-1α and Clq were investigated by RT-PCR, Elisa and Western blot in vitro. And JNK phosphorylation was determined using Western blot. Results GSPs significantly reduced the expression of C3d and Clq of Al AS markers and inhibited the phosphorylation of JNK. Moreover, compared with the model group, GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6, IL-1 α, IL-17 and H

Objective To explore the role pathway and pattern of the transcription factor myeloma cancer gene (MYC) and its mRNA interaction with microRNA(miRNA, miR) and ciccular RNA(circRNAs) at 0 hour and 6 hour in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy，PH) model was prepared as described by Higgins, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNAs(ceRNA) of remnant liver were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hours after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-540-3p displays 3.00±0.43 and 0.79±0.01, circRNA_04996 showed 1.43±0.43 and 3.14±0.94. At the same time, the four kinds of inflammatory reaction-related genes plasminogen activator urokinase receptor (PLAUR), tumor necrosis factor (TNF), interleukin 1 receptor type 2 (IL1R2), ect, which were prometed in expression by MYC, were down-regulated at 0 hour after PH, but the inflammatory reaction-related genes natriuretic peptide A (NPPA), nuclear receptor subfamily O group B member 2 (NROB2) and peroxisome proliferator activated receptor alpha (PPARA), which were inhibited in expression by MYC, were up-regulated at 0 hour after PH. On the other hand, the three kinds of inflammatory reaction-related genes PLAUR, TNF, IL1R2, ect, which are prometed in expression by MYC, were up-regulated at 6 hours after PH, but the inflammatory reaction-related genes NPPA, NROB2 and PPARA, which were inhibited in expression by MYC, were down-regulated at 6 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the inflammatory reaction-related genes, which are regulated by MYC, and are helpful for the hepatocyte to be in non-inflammatory reaction state at 0 hour after PH and to be in inflammatory reaction state at 6 hours after PH.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.