Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVES: To assess the effectiveness of the comparison between pit and fissure sealants and fluoride varnishes, as well as various types of sealants, in preventing caries on the occlusal surface of children's first permanent molars (FPM). METHODS: Conduct a comprehensive search of literature published between January 1, 1988, and May 30, 2024, in the following databases: China National Knowledge Infrastructure, Web of Science, Cochrane Library, Embase, PubMed, China Science Periodical Database and China Biology Medicine database. Meta-analysis and subgroup analyses were performed on the literature that met the inclusion criteria. RESULTS: A total of 5 618 pieces of literature were retrieved, resulting in the inclusion of 14 in the study. Meta-analysis showed that there was no statistically significant difference in the efficacy between varies pit and fissure sealants compared to fluoride varnishes, and between varies types of sealants in preventing caries on the occlusal surface of children's first permanent molars within 24 months post-surgery (P>0.05). CONCLUSIONS Within 24 months, there was no significant difference in the effectiveness of using resin-based or glass iomomer pit and fissure sealants compared with fluoride varnishes in preventing occlusal caries in FPM in children; within 24 months, there was no significant difference in the effectiveness of using resin-based sealants compared with ART sealants in preventing occlusal caries in FPM in children. ART sealants are recommended over resin-based sealers for children who have no conditions for chair-side manipulation or who are poorly co-operative.
Humans ; Pit and Fissure Sealants/therapeutic use* ; Dental Caries/prevention & control* ; Molar ; Child ; Fluorides, Topical/therapeutic use* ; Dentition, Permanent

BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.

Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.

This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

Objective To investigate the correlation between serum levels of microRNA(miR)-489-3p and miR-214-3p in patients with Psoriasis and the severity of disease.Methods From March 2022 to January 2024,138 Psoriasis patients who visited Zhangjiakou First Hospital were regarded as the study subjects(disease group).According to the psoriasis area and severity index(PASI)score,the 138 Psoriasis patients were separated into mild group(n=46),moderate group(n=54)and severe group(n=38).112 healthy individuals who underwent physical examinations in Zhangjiakou First Hospital during the same period were included in the control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the serum levels of miR-489-3p and miR-214-3p in the subjects.The serum levels of miR-489-3p and miR-214-3p were compared between the disease group and the control group,and among patients with different degrees of disease.Spearman correlation analysis was applied to explore the relationship between serum miR-489-3p,miR-214-3p levels and disease severity in Psoriasis patients.Logistic regression analysis was performed to analyze the related factors affecting the severity of Psoriasis.Receiver operating characteristic(ROC)curve was applied to investigate the diagnostic value of serum miR-489-3p and miR-214-3p levels for severe Psoriasis.Results The serum levels of miR-489-3p(0.81±0.23)and miR-214-3p(0.79±0.22)in the disease group were lower than those in the control group(1.05±0.28,1.02±0.25),and the differences were statistically significant(t=7.441,7.732,all P<0.05).Serum miR-489-3p in mild,moderate and severe Psoriasis groups(0.93±0.24,0.80±0.23,0.69±0.22),miR-214-3p levels(0.91±0.24,0.77±0.22,0.66±0.21)decreased gradually,and the differences were statistically significant(F=12.423,13.168,all P<0.05).Spearman's results showed that serum levels of miR-489-3p and miR-214-3p were negatively correlated with the severity of Psoriasis in patients(r=-0.490,-0.463,all P<0.05).Serum miR-489-3p and miR-214-3p were independent protective factors for the severity of Psoriasis patients(Wald χ2=5.751,8.753,all P<0.05).ROC curve results showed that the area under the curve(AUC)of serum miR-489-3p and miR-214-3p for diagnosing severe Psoriasis alone was 0.785 and 0.792,with sensitivity of 78.9%and 73.7%,specificity of 49.9%and 54.7%,respectively.The AUC of the combined diagnosis for severe Psoriasis was 0.931,the sensitivity and specificity were 71.7%,71.1%,respectively,and the combined diagnostic efficacy of the two was better than that of miR-489-3p and miR-214-3p alone,and the differences were statistically significant(Z=3.018,2.773,all P<0.05).Conclusion The serum levels of miR-489-3p and miR-214-3p in patients with Psoriasis are both reduced,and both are negatively correlated with the severity of the disease in Psoriasis patients.The combined determination of the two has high efficacy in the diagnosis of severe Psoriasis.

BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.

Objective To investigate the correlation between serum levels of microRNA(miR)-489-3p and miR-214-3p in patients with Psoriasis and the severity of disease.Methods From March 2022 to January 2024,138 Psoriasis patients who visited Zhangjiakou First Hospital were regarded as the study subjects(disease group).According to the psoriasis area and severity index(PASI)score,the 138 Psoriasis patients were separated into mild group(n=46),moderate group(n=54)and severe group(n=38).112 healthy individuals who underwent physical examinations in Zhangjiakou First Hospital during the same period were included in the control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the serum levels of miR-489-3p and miR-214-3p in the subjects.The serum levels of miR-489-3p and miR-214-3p were compared between the disease group and the control group,and among patients with different degrees of disease.Spearman correlation analysis was applied to explore the relationship between serum miR-489-3p,miR-214-3p levels and disease severity in Psoriasis patients.Logistic regression analysis was performed to analyze the related factors affecting the severity of Psoriasis.Receiver operating characteristic(ROC)curve was applied to investigate the diagnostic value of serum miR-489-3p and miR-214-3p levels for severe Psoriasis.Results The serum levels of miR-489-3p(0.81±0.23)and miR-214-3p(0.79±0.22)in the disease group were lower than those in the control group(1.05±0.28,1.02±0.25),and the differences were statistically significant(t=7.441,7.732,all P<0.05).Serum miR-489-3p in mild,moderate and severe Psoriasis groups(0.93±0.24,0.80±0.23,0.69±0.22),miR-214-3p levels(0.91±0.24,0.77±0.22,0.66±0.21)decreased gradually,and the differences were statistically significant(F=12.423,13.168,all P<0.05).Spearman's results showed that serum levels of miR-489-3p and miR-214-3p were negatively correlated with the severity of Psoriasis in patients(r=-0.490,-0.463,all P<0.05).Serum miR-489-3p and miR-214-3p were independent protective factors for the severity of Psoriasis patients(Wald χ2=5.751,8.753,all P<0.05).ROC curve results showed that the area under the curve(AUC)of serum miR-489-3p and miR-214-3p for diagnosing severe Psoriasis alone was 0.785 and 0.792,with sensitivity of 78.9%and 73.7%,specificity of 49.9%and 54.7%,respectively.The AUC of the combined diagnosis for severe Psoriasis was 0.931,the sensitivity and specificity were 71.7%,71.1%,respectively,and the combined diagnostic efficacy of the two was better than that of miR-489-3p and miR-214-3p alone,and the differences were statistically significant(Z=3.018,2.773,all P<0.05).Conclusion The serum levels of miR-489-3p and miR-214-3p in patients with Psoriasis are both reduced,and both are negatively correlated with the severity of the disease in Psoriasis patients.The combined determination of the two has high efficacy in the diagnosis of severe Psoriasis.

Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.

Objective:To analyze the role of learning engagement and learning burnout in the relationship between supervisors' guidance and the personal ability of postgraduates in the Professional Master's Program in Clinical Medicine.Methods:A total of 4 016 postgraduates in the Professional Master's Program in Clinical Medicine from 61 colleges were surveyed in 2020. Common method bias was assessed using the Harman's single factor test and total score was determined by the entropy weight method. Causality and mediation effect were analyzed by linear regression, and mediation effect was tested by Bootstrapping.Results:The average scores of supervisors' guidance, learning burnout, learning engagement and personal ability were (4.13±0.87), (2.49±1.11), (3.88±0.83), and (3.71±0.78), respectively. Supervisors' guidance significantly and positively impacted learning engagement ( β=0.689, P<0.001) and personal ability ( β=0.504, P<0.001). Learning engagement played a partial mediating role (89.30% of mediation effect) between supervisors' guidance and personal ability. Learning burnout (interaction term β=0.078, P<0.001) positively regulated the relationship between supervisors' guidance and learning engagement. Conclusions:Learning engagement can mediate the effect of supervisors' guidance on the personal ability of postgraduates in the Professional Master's Program in Clinical Medicine, and learning burnout positively regulates the effect of supervisors' guidance on learning engagement. Strengthened supervisors' guidance, increased attention to students' learning burnout, and enhanced learning engagement can further improve the personal abilities of postgraduates in the Professional Master's Program in Clinical Medicine.