Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Objective: To investigate the protective effects and mechanisms of acellular nerve allografts (ANA) on motor neurons in the spinal cord anterior horn of sciatic nerve injury ( SNI) rats . Methods: SPF grade male SD rats were randomly divided into normal , model , ANA-bridged (bridge group) , and autologous nerve transplantation groups (autograft group) , with 6 rats in each group . The SNI rat model was established using the right sciatic nerve clamp method for 10 mm . In the bridge group , the ANA was bridged to the two severed ends of the injured sciatic nerve , and in the autograft group , the autologous nerves were flipped head to tail and then bridged to the two se- vered ends . A spectrophotometer was applied to determine the DNA content in normal nerves and ANA . The foot- print test was used to determine the sciatic nerve function index (SFI) of the rats in each group , the wet weight ra- tio of the anterior tibialis muscle was calculated . The morphology and structure of the anterior horn motor neurons of the spinal cord of each group were observed by HE staining. The immunofluorescence and Western blot were used to detect Apaf-1 , Caspase-3 , Bcl-2 , Bax , and Cyt-C proteins expression in the L4-6 segment of the spinal cord . Results: The DNA content in the ANA prepared in this study was significantly lower than that in normal nerves (P < 0. 05) . Compared with the normal group , the SFI and wet weight ratio of the anterior tibialis muscle were re- duced in the model group (P < 0. 001) ; compared with the model group , both SFI and wet weight ratio of the ante- rior tibialis muscle significantly increased in the bridge group and the autografts group ( P < 0. 05 , P < 0. 001) , and the SFI and wet weight ratio of the anterior tibialis muscle in the autograft group were higher than those in the bridge group (P < 0. 001 , P < 0. 01) . The results of HE staining showed that the motor neurons in the anterior horn of the spinal cord of the normal group were structurally intact and had clear cytosolic boundaries; the neurons in the model group were lysed and necrotic , with blurred cytosolic boundaries; the neurons in the bridge group were less lysed and necrotic , but the nuclear translocation phenomenon could still be seen; the neurons in the autograft group were morphologically and structurally intact with clear cytosolic boundaries . Compared with the normal group , the expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins significantly increased in the model group (P < 0. 001 , P < 0. 01 , P < 0. 01 , P < 0. 05) . Compared with the model group , the expression of Apaf-1 , Caspase- 3 , Bax , and Cyt-C proteins significantly decreased (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) ; but the expres- sion of Bcl-2 protein significantly increased in the bridge group and the autograft group (P < 0. 05) . The expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins in the autografts group was lower than that in the bridge group (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) . Conclusion ANA can exert a protective effect on motor neurons in the anterior horn of the spinal cord of SNI rats by improving the morphology and structure of neurons , increasing the ex- pression of Bcl-2 protein , but decreasing the expression of Cyt-C , Bax , Caspase-3 , and Apaf-1 proteins in the spi- nal cord . The mechanism of ANA may be related to the Bcl-2/Cyt-C/Apaf-1-mediated mitochondrial apoptosis sig- naling pathway .

【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.

Objective Based on the Integrated Theory of Health Behavior Change(ITHBC),the influencing factors of home medication safety were explored in patients with chronic heart failure(CHF).Methods This qualitative de-scription,involving a semi-structured in-depth interview of 22 CHF patients based on purposive sampling,was con-ducted from December 2022 to May 2023,at 3 hospitals in Changsha,Hunan.NVivo 11.0 software was used to or-ganize and code data,and content analysis was performed to analyze data.Results Totally 9 generic categories be-longing to 4 categories were extracted.These were knowledge(knowledge of disease and knowledge of medication safety),attitude and belief(attitude towards diseases and medication belief),self-regulation(participation in medica-tion safety self-management and growing through experience),and social facilitation(hospital consultation services,family support and objective situation interference).Conclusion Knowledge,belief,self-regulation and social facili-tation were interrelated to influence medication safety behavior of patients with CHF at home.Medical workers,family members and society should work together to provide medication safety information,create a supportive envi-ronment,focus on improving patients'awareness and ability of self-regulation,strengthen their belief in taking medi-cation,and ultimately ensure the home medication safety for CHF patients.