BACKGROUND:Currently,a variety of mesenchymal stem cells have been confirmed to have the effect of promoting wound repair,but there is still a lack of relevant research on whether placenta-derived mesenchymal stem cells can promote acute skin wound healing. OBJECTIVE:To investigate the effect of placenta-derived mesenchymal stem cell transplantation on the healing of acute skin wound in rats. METHODS:Twenty SD rats were divided into PBS group and stem cell group by the random number table method,with 10 rats in each group.All rats were selected to establish a full-thickness skin defect model.In the PBS group and stem cell group,PBS buffer and placenta-derived mesenchymal stem cells were immediately injected on the wound surface and wound margin immediately and on day 8 after modeling.The wound healing was observed immediately and on days 2,4,6,8,10,12,and 14 after modeling.The skin tissue of the wound surface was taken on day 14 and treated with hematoxylin-eosin staining,Masson staining,immunohistochemical staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The wound surface of the rats in each group decreased with the prolongation of treatment time.The wound healing rate and wound epithelization rate of the stem cell group at 14 days were higher than those of the PBS group(P<0.01),and the wound contracture rate was lower than that of the PBS group(P<0.01).(2)The results of hematoxylin-eosin staining showed that the skin wound healing of the stem cell group was better than that of the PBS group;the degree of wound epithelization was higher,and the morphology of collagen fibers was close to that of normal skin.(3)Masson staining results showed that compared with the PBS group,collagen fibers in the skin wound tissue of the stem cell group were significantly increased and thicker,and the content of collagen fibers in the new tissue was significantly higher than that of the PBS group(P<0.01).(4)Immunohistochemical staining showed that the number of new capillaries in the stem cell group was higher than that in the PBS group(P<0.01),while the expressions of tumor necrosis factor-α and interleukin-6 were lower than those in the PBS group(P<0.01).(5)Immunofluorescence staining showed that the number of M2 macrophages in the new wounds of the stem cell group was higher than that of the PBS group(P<0.01),while the number of M1 macrophages was less than that in the PBS group(P<0.01).These findings indicate that placenta-derived mesenchymal stem cells can accelerate skin wound healing,promote wound epithelization,and reduce wound contracture,which may be related to the promotion of capillary angiogenesis,regulation of collagen fiber production,inhibition of inflammation,and regulation of macrophage polarization to M2 type.

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

Diabetic wound is a complication of diabetes, which is difficult to heal and easy to turn into chronic wound. Compared with ordinary wound healing, diabetic wounds stay in the inflammatory stage and can not enter the proliferative stage. This is because the proportion of pro-inflammatory cytokines increases, leading to the imbalance of inflammatory cells and the accumulation of a large number of inflammatory factors. The production and release of inflammatory factors is closely related to pyroptosis. Pyroptosis is a kind of programmed death mode of inflammatory cells. Mediated by inflammasome, pyroptosis is transduced through typical and atypical inflammasome signaling pathways, resulting in the formation of pores on the cell membrane and inducing cell death. In this process, a large number of pro-inflammatory cytokines are released to maintain the inflammatory environment of wounds, hindering the development of diabetic wounds to the proliferative stage and remodeling stage, thus inhibiting the healing of diabetic wounds. This article reviews the mechanism of pyroptosis and its effect on diabetic wounds, the potential significance of inhibiting pyroptosis in the treatment of diabetic wounds, and the existing problems.

In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

Ferroptosis is a form of programmed cell death characterized by iron metabolic imbalance and lipid peroxidation.Alzheimer disease(AD)is a neurodegenerative condition.Studies have shown that lipid peroxidation through ferroptosis plays a significant role in the progression of AD.Ferroptosis suppressor protein 1(FSP1)/coenzyme Q10(CoQ10)signaling axis serves as a crucial regulatory element in the process of lipid peroxidation associated with ferropto-sis.This review explores the mechanisms of the FSP1/CoQ10 signaling axis in AD,aiming to present a novel therapeutic ap-proach for AD treatment.

Purpose: This study aimed to determine the optimal cutoff points for age and tumor size of patients with intrahepatic cholangiocarcinoma (ICC) and to establish and verify a predictive nomogram of overall survival at 1, 3, and 5 years. Methods: From the SEER (Surveillance, Epidemiology, and End Results) database, 1,325 ICC patients were selected and randomly divided into training and testing cohorts at a 7:3 ratio. Using the X-tile software, age and tumor size were classified into 3 subgroups: ≤61, 62–74, and ≥75 years and ≤35, 36–55, and ≥56 mm. Subsequently, univariate and multivariate Cox regression analyses were performed using the R software in the training cohort to determine independent risk factors, compile the prediction nomogram, and verify it with the testing cohort findings. Results: The C-indexes of the new prediction nomograms in the training and testing cohorts were 0.738 (95% confidence interval [CI], 0.718–0.758) and 0.750 (95% CI, 0.72–0.78), respectively. Furthermore, the areas under the 1-, 3-, and 5-year receiver operating characteristic (ROC) curves based on the nomogram were 0.792, 0.853, and 0.838, respectively, higher than the ROC based on the 7th and 8th editions of the American Joint Cancer Commission (AJCC) staging system. Conclusion This study established and verified a prognostic nomogram that improved the accuracy of the 1-, 3-, and 5-year survival predictions for ICC patients, compared with that based on the 7th and 8th editions of the AJCC staging system, and can help clinicians make personalized survival predictions.

Objective:To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF).Methods:This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke.Results:Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion:Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

Objective To evaluate the effect of pulsed radiofrequency (PRF) on spinal adenosine triphosphate (ATP)-P2X4-NLRP3 signaling pathway in rats with neuropathic pain.Methods Forty healthy clean-grade adult male Sprague-Dawley rats,aged 2-3 months,weighing 220-260 g,were divided into 4 groups (n =10 each) using a random number table method:sham operation group (group S),neuropathic pain group (group NP),sham PRF group (group SPRF) and PRF group.Neuropathic pain was induced by chronic constriction injury to the left sciatic nerve of anesthetized rats.Rats received PRF treatment on 7th day after establishing the model in group PRF.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before establishing the model (T0) and at 3,7,10,14,21 and 28 days after establishing the model (T1-6).The rats were then sacrificed and the spinal cord was removed for determination of P2X4 and NLRP3 expression (by Western blot) and interleukin-1beta (IL-1β),IL-2,IL-6 and tumor necrosis factor-alpha (TNF-α) contents (by enzymelinked immunosorbent assay).Results Compared with group S,the MWT and TWL were significantly decreased at T1-6,the expression of P2X4 and NLRP3 was up-regulated,and the contents of IL-1β,IL-2,IL-6 and TNF-α were increased in NP,SPRF and PRF groups (P＜0.05).Compared with group NP and group SPRF,the MWT and MWT were significantly increased at T3-6,the expression of P2X4 and NLRP3 was down-regulated,and the contents of IL-1 β,IL-2,IL-6 and TNF-α were decreased in group PRF (P＜0.05).Conclusion The mechanism by which PRF alleviates neuropathic pain is related to inhibiting ATP-P2X4-NLRP3 signaling pathway in rats.

Objective To evaluate the effect of prostaglandin E1 (PGE1) on propofol-induced neuroapoptosis in hippocampus of newborn rats.Methods Thirty-six clean-grade healthy newborn SpragueDawley rats,aged 7 days,weighing 11-16 g,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),propofol group (group P) and group PGE1.Propofol 75 mg/kg was intraperitoneally injected once every other day for 7 consecutive days in P and PGE1 groups.PGE1 10 μg/kg was injected via the tail vein at 30 min before each injection of propofol in group PGE1.Normal saline 3 ml/kg was intraperitoneally injected once every other day for 7 consecutive days in group C.The rats were sacrificed at 60 min after emergence from the last injection.The hippocampi were harvested for determination of neuroapoptosis (by TUNEL),expression of caspase-3,Bcl-2 and Bax (by Western blot),and contents of intedeukin-1bota (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbont assay).Results Compared with group C,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly increased,apoptosis index was increased,the expression of caspase-3 and Bax was up-regulated,and the expression of Bcl-2 was down-regulated in P and PGE1 groups (P＜0.05).Compared with group P,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly decreased,apoptosis index was decreased,the expression of caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group PGE1 (P＜0.05).Conclusion PGE1 can reduce propofol-induced neuroapoptosis in hippocampus of newborn rats,and the mechanism may be related to inhibiting inflammatory responses of the hippocampus.