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 polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

BACKGROUND:Percutaneous vertebroplasty is the most widely used method for the treatment of osteoporotic vertebral compression fractures,and most studies have concluded that percutaneous vertebroplasty increases the probability of adjacent vertebral secondary compression fractures in patients with osteoporotic vertebral compression fractures.However,controversy remains regarding the risk factors associated with adjacent vertebral re-fracture caused after percutaneous vertebroplasty. OBJECTIVE:To summarize the influencing factors of adjacent vertebral compression fractures after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures,in order to provide a certain reference for reducing the risk of its occurrence as well as formulating the corresponding treatment plan. METHODS:Using"osteoporosis,fracture,percutaneous vertebroplasty,adjacent vertebral compression fractures,risk factors"as the Chinese search terms,"osteoporosis,osteoporotic vertebral compression fractures,percutaneous vertebroplasty,adjacent vertebral compression fractures,risk factors"as English search terms,computerized searches were conducted on CNKI,Wanfang Medical Network,VIP,PubMed,Springer,ScienceDirect,and Elsevier databases.The search timeframe focuses on January 2018 through September 2023,with the inclusion of a few classic forward literature.The literature was screened by reading the titles and abstracts,and 83 papers were finally included in the review. RESULTS AND CONCLUSION:(1)Osteoporotic vertebral compression fractures are one of the most common complications of osteoporosis,placing elderly patients at a significant risk of disability and death.Percutaneous vertebroplasty is a practical and effective treatment for osteoporotic vertebral compression fractures.(2)With the popularity of percutaneous vertebroplasty,its secondary vertebral compression fractures have gradually increased,with adjacent vertebral compression fractures being the most common.(3)Previous studies have only discussed the effects of factors such as bone mineral density,multiple vertebral fractures,body mass index,age,sex,amount of bone cement,cement leakage,and anti-osteoporosis treatment on secondary compression fractures of adjacent vertebrae after percutaneous vertebroplasty,and summarized the number of vertebral fractures,timing of the operation,surgical approach,cement material,diffuse distribution of bone cement,recovery height of the injured vertebrae,and wearing of a support after surgery,which is not yet comprehensive.The analysis of the specific mechanisms of risk factor-induced adjacent vertebral fractures is relatively rare.(4)The results of the article showed that low bone mineral density,advanced age,perimenopausal women,multiple vertebral fractures,excessive recovery of the height of the injured vertebrae,cement leakage,comorbid underlying diseases,and poor lifestyle habits were the risk factors for secondary adjacent vertebral compression fractures after percutaneous vertebroplasty,and that maintaining a normal body mass index,early surgery,bilateral percutaneous vertebroplasty,use of a new type of cement material,an appropriate volume of bone cement injection and uniform cement dispersion,regular anti-osteoporosis treatment,and postoperative brace wearing are protective factors for secondary adjacent vertebral compression fractures after percutaneous vertebroplasty.

Posterior lumbar interbody fusion (PLIF) is currently well accepted and considered as safe and effective spinal surgical technique for the treatment of degenerative lumbar spondylolisthesis, and is widely used in clinical practice. But there are still some cases with poor overall postoperative efficacy. In order to discuss the relevant factors and mechanisms affecting the clinical outcomes of PLIF surgery, many scholars have conducted a large number of clinical studies over the years. However, due to the different methods and the factors among included studies, the conclusions reached were also different or even completely opposed. This article reviews the research results of various influencing factors of the postoperative efficacy of PLIF in recent years, and analyzes age, gender, body mass index, bone mineral density, duration of preoperative symptoms, whether the sliding vertebral body is reduced, spine-pelvic sagittal parameters (including lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, pelvic incidence-lumbar lordosis and Roussouly classification) and other factors (underlying diseases and poor lifestyle habits) on the clinical effects of PLIF, in order to provide a reference for further improving the postoperative quality of life and functional recovery of patients with degenerative lumbar spondylolisthesis.

Objective:To explore the significance of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in the treatment of hypertensive basal ganglia cerebral hemorrhage.Methods:The clinical data of 60 patients with hypertensive basal ganglia cerebral hemorrhage, who underwent CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in Beijing Luhe Hospital, Capital Medical University from January 2018 to December 2022, were retrospectively analyzed. The surgical related indexes and adverse reactions were recorded. The patients were followed up for 6 months, and the prognosis was evaluated using the Glasgow outcome score (GOS).Results:A total of 60 cases of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage were all successfully performed, and the operation time was (53 ± 18) min. There were 2 cases (3.3%) of postoperative puncture path hematoma, which were completely resolved with conservative treatment. The expansion of postoperative intracerebral hematoma was not observed. The drainage tube retention after operation ≤2 d was in 44 cases (73.3%), and the drainage tube retained for 3 to 4 d was in 16 cases (26.7%), all of them had no intracranial infection after operation. Fifteen cases (25.0%) were complicated with severe pneumonia after operation, and 2 cases (3.3%) died due to severe pneumonia combined with multiple organ failure. Follow up at 6 months after operation, 17 cases (28.3%) were good, 19 cases (31.7%) had mild disability, 16 cases (26.7%) had severe disability, 6 cases (10.0%) had vegetative survival status, and 2 cases (3.3%) died.Conclusions:The CAS-R-2 frameless brain stereotactic instrument assisted trepanation and drainage for the treatment of hypertensive basal ganglia cerebral hemorrhage has the characteristics of simple operation, accurate positioning, minimal trauma, and fewer complications. It is a safe and effective method for treating hypertensive basal ganglia cerebral hemorrhage.