BACKGROUND:Acute liver injury can result from a variety of causes,and if not treated in time,it will develop into acute liver failure and seriously affect the life safety of patients.As the liver is the largest immune organ and metabolic organ,there is no optimal treatment for acute liver injury.The adipose tissue-derived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity,so it has been gradually becoming an effective tool for the treatment of acute liver injury.OBJECTIVE:To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury.METHODS:Relevant articles published from 2000 to 2023 were retrieved from PubMed,Web of Science,and CNKI databases.English search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,cell surface engineering,stem cell modification."Chinese search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,stem cell modification."Totally 62 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury.Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell,they are more widely sourced,easily accessible and have fewer ethical issues,and more self-renewal than bone marrow mesenchymal stem cell.(2)Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses,differentiating into hepatocytes,and secreting growth factors and exosomes.It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue,also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte,and ultimately improve liver damage.At present,no studies have shown which mechanism is the best mechanism for adipose tissue-derived mesenchymal stem cells to treat acute liver injury,and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment.(3)Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.On the one hand,biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell,such as enhancing the ability of proliferation and migration,increasing the level of growth factors secreted,and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site.On the other hand,biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation.(4)In summary,adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes,regulating the immune response,and promoting liver regeneration.With the development of science and technology,biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury.It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.

Objective:To explore the effect of inhibiting miR-203a-3p gene expression on proliferation and apoptosis of rheu-matoid arthritis(RA)synovial fibroblasts.Methods:Divided fibroblast-like synovial cells MH7A into Control group(untransfected cells),anti-miR-NC group(transfected with anti-miR-NC),anti-miR-203a-3p group(transfected with anti-miR-203a-3p),anti-miR-203a-3p+LiCl group(transfected with anti-miR-203a-3p+signal pathway activator LiCl).qRT-PCR was used to detect expression level of miR-203a-3p;clone formation experiment,MTT experiment were used to detect cell proliferation;flow cytometry was used to de-tect cell apoptosis;Western blot was used to detect protein expressions of PCNA,Bcl-2,Bax,Wnt1,β-catenin.Results:Transfec-tion of miR-203a-3p reduced the number of clones and survival rate of MH7A cells,increased rate of apoptosis,reduced expression levels of PCNA,Bcl-2,Wnt1,β-catenin protein,increased expression level of Bax protein.The signaling pathway activator LiCl in-creases the number of clones and survival rate of MH7A cells transfected with miR-203a-3p,reduces the rate of apoptosis,increases the expression level of Wnt1,β-catenin,PCNA,Bcl-2 protein,and reduces expression level of Bax protein.Conclusion:miR-203a-3p may promote proliferation of RA synovial fibroblasts and inhibit cell apoptosis by activating Wnt/β-catenin.

Objective:To explore the effect of inhibiting miR-203a-3p gene expression on proliferation and apoptosis of rheu-matoid arthritis(RA)synovial fibroblasts.Methods:Divided fibroblast-like synovial cells MH7A into Control group(untransfected cells),anti-miR-NC group(transfected with anti-miR-NC),anti-miR-203a-3p group(transfected with anti-miR-203a-3p),anti-miR-203a-3p+LiCl group(transfected with anti-miR-203a-3p+signal pathway activator LiCl).qRT-PCR was used to detect expression level of miR-203a-3p;clone formation experiment,MTT experiment were used to detect cell proliferation;flow cytometry was used to de-tect cell apoptosis;Western blot was used to detect protein expressions of PCNA,Bcl-2,Bax,Wnt1,β-catenin.Results:Transfec-tion of miR-203a-3p reduced the number of clones and survival rate of MH7A cells,increased rate of apoptosis,reduced expression levels of PCNA,Bcl-2,Wnt1,β-catenin protein,increased expression level of Bax protein.The signaling pathway activator LiCl in-creases the number of clones and survival rate of MH7A cells transfected with miR-203a-3p,reduces the rate of apoptosis,increases the expression level of Wnt1,β-catenin,PCNA,Bcl-2 protein,and reduces expression level of Bax protein.Conclusion:miR-203a-3p may promote proliferation of RA synovial fibroblasts and inhibit cell apoptosis by activating Wnt/β-catenin.

BACKGROUND:Acute liver injury can result from a variety of causes,and if not treated in time,it will develop into acute liver failure and seriously affect the life safety of patients.As the liver is the largest immune organ and metabolic organ,there is no optimal treatment for acute liver injury.The adipose tissue-derived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity,so it has been gradually becoming an effective tool for the treatment of acute liver injury.OBJECTIVE:To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury.METHODS:Relevant articles published from 2000 to 2023 were retrieved from PubMed,Web of Science,and CNKI databases.English search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,cell surface engineering,stem cell modification."Chinese search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,stem cell modification."Totally 62 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury.Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell,they are more widely sourced,easily accessible and have fewer ethical issues,and more self-renewal than bone marrow mesenchymal stem cell.(2)Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses,differentiating into hepatocytes,and secreting growth factors and exosomes.It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue,also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte,and ultimately improve liver damage.At present,no studies have shown which mechanism is the best mechanism for adipose tissue-derived mesenchymal stem cells to treat acute liver injury,and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment.(3)Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.On the one hand,biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell,such as enhancing the ability of proliferation and migration,increasing the level of growth factors secreted,and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site.On the other hand,biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation.(4)In summary,adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes,regulating the immune response,and promoting liver regeneration.With the development of science and technology,biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury.It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.

Home rehabilitation is the main rehabilitation model for elderly patients with hip fractures in China, and the application of digital health technology shows great potential in improving the quality of home rehabilitation for this population. This paper describes the concept of digital health technology, the current application status of different types of digital health technology in home rehabilitation for elderly patients with hip fractures, and discusses existing issues and future prospects, aiming to provide a reference for digital home rehabilitation nursing for elderly hip fracture patients.

Objective To study the correlation between expression levels of serum Spexin and Pannexin 1 protein,glucose and lipid metabolism and insulin resistance in elderly patients with diabetic cataract.Methods A total of 118 elderly diabetic cataract patients were selected as the case group,and 103 elderly diabetic non-cataract patients were selected as the control group who were treated in the same hospital during the same period.Serum levels of Spexin and Pannexin1 were detected by enzyme-linked immunosorbent assay(ELISA).Fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)were measured.Lipid metabolism related indicators including triacylglycerol(TG),high density lipoprotein cholesterol(HDL-C),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)were detected in two groups of patients.Insulin resistance related indexes:fasting insulin(FINS),insulin sensitivity index(ISI),insulin resistance index(HOMA-IR)and islet beta cell function index(HOMA-β)were also detected.The correlation between serum Spexin and Pannexin1 levels,glucolipid metabolism and ISI was detected by Pearson method.Receiver operating characteristic(ROC)curves were used to assess the predictive value of serum Spexin and Pannexin1 levels and their combination in the development of cataract in elderly diabetic patients.Results The level of Spexin was lower in the observation group than that in the control group,and the level of Pannexin1 was higher than that in the control group(P＜0.01).Levels of TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR of the observation group increased compared with the control group,while HDL-C,ISI and HOMA-β levels decreased compared with the control group(P＜0.01).Pearson correlation analysis showed that serum Spexin level was positively correlated with ISI and HOMA-β,and negatively correlated with TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR in elderly patients with diabetic cataract(P＜0.05).Serum Pannexin1 was negatively correlated with ISI and HOMA-β,and positively correlated with TG,TC,LDL-C,FPG,HbA1c,FINS and HOMA-IR(P＜0.05).There was no correlation between the above indexes and HDL-C(P＞0.05).The combination of both serum Spexin and Pannexin1 predicted the development of cataracts in elderly diabetic patients was better than serum Spexin and Pannexin1 assessed individually(Z both combination-Spexin=3.220,P=0.001,Z both combination-Pannexin1=4.838,P＜0.001).Conclusion In elderly patients with diabetic cataract,the expression of serum Spexin decreases and the expression of Pannexin1 increases,and they have a certain correlation with glucose and lipid metabolism and insulin resistance

Home rehabilitation is the main rehabilitation model for elderly patients with hip fractures in China, and the application of digital health technology shows great potential in improving the quality of home rehabilitation for this population. This paper describes the concept of digital health technology, the current application status of different types of digital health technology in home rehabilitation for elderly patients with hip fractures, and discusses existing issues and future prospects, aiming to provide a reference for digital home rehabilitation nursing for elderly hip fracture patients.

Endoplasmic reticulum stress(ERS)plays a crucial role in cellular self-protection.In response to environmental changes,cells activate the unfolded protein response(UPR)and endoplasmic reticulum-associated protein degradation pathways to restore homeostasis.Increasing experimental evidence indicates that hypoxia and inflammation negatively impact synoviocytes in rheumatoid arthritis(RA),leading to the activation of three key endoplasmic reticulum transmembrane proteins:inositol-requiring enzyme 1,protein kinase R-like endoplasmic reticulum kinase,and activating transcription factor 6.These proteins mediate UPR pathways that are implicated in the pathological progression of RA.Targeting ERS-related molecules has emerged as a promising therapeutic strategy for RA.This article reviews the impact of ERS on the pathogenesis of RA and discusses drugs that modulate ERS as potential treatments for the disease.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.