Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Lipedema is a disease in which local fat deposits in the body are the main clinical manifestations. It is often characterized by a disproportionate increase in subcutaneous fat tissue in the extremities, buttocks or hip joints. It is often misdiagnosed as obesity or lymphedema in clinical practice. The pathogenesis is not clearly understood, and there is no standardized clinical treatment method. This paper elaborated on the research status of the pathogenesis of lipedema, and summarized the clinical manifestations and classification, diagnosis and differential diagnosis, treatment methods, etc., aiming to provide up-to-date perspectives of lipedema.

Lipedema is a disease in which local fat deposits in the body are the main clinical manifestations. It is often characterized by a disproportionate increase in subcutaneous fat tissue in the extremities, buttocks or hip joints. It is often misdiagnosed as obesity or lymphedema in clinical practice. The pathogenesis is not clearly understood, and there is no standardized clinical treatment method. This paper elaborated on the research status of the pathogenesis of lipedema, and summarized the clinical manifestations and classification, diagnosis and differential diagnosis, treatment methods, etc., aiming to provide up-to-date perspectives of lipedema.

Sleep disorders are characterized by abnormal amounts of sleep and unusual behavior during sleep.Long-term sleep disorders can lead to the disruption of normal social functioning or neurological conditions.In recent years,the role of sound wave therapy in improving sleep quality has attracted much attention.This article aims to review the research progress related to the role of sound wave therapy in enhancing sleep quality,cognitive function,and alleviating fatigue in patients with sleep disorders in hopes of contributing to clinical applications.

Objective To explore the effect of multiparameter electroencephalogram(EEG)-guided anesthesia management on EEG burst suppression(BS)and postoperative delirium(POD)in elderly patients undergoing lower abdominal laparoscopic surgery.Methods A total of 100 elderly patients,48 males and 52 females,aged 65-85 years,BMI 18.5-28.0 kg/m2,and ASA physical status Ⅱ or Ⅲ,were enrolled for lower abdominal surgery under general anesthesia.Patients were randomly divided into two groups:multiparameter group and single parameter group,50 patients in each group.In multiparameter group,multiparameter EEG monitoring with patient statu index(PSI),spectral edge frequency(SEF),burst suppression ratio(BSR)and density spectral array(DSA)were used to guide the depth management of anesthesia.In single parameter group,single parameter PSI was used to guide the depth management of anesthesia.The total area under the hypotensive threshold of MAP(AUTMAP)was calculated,and the amount of anesthetic used during the operation and the use of vasoactive drugs,duration of anesthesia,extu-bation time,duration of PACU stay,and postoperative hospitalisation days were recorded.HR,MAP,PSI,and SEF were recorded before the induction of anesthesia,5 minutes after induction of anesthesia,5,30,and 60 minutes after incision,and at the end of surgery.The incidence,duration,and maximum BSR of in-traoperative BS,as well as the incidence of POD 1,2,and 3 days after surgery were recorded.Results There was no significant difference in AUTMAP values between the two groups.Compared with single parame-ter group,intraoperative propofol and remifentanil dosage were significantly decreased(P＜0.05),awak-ening time,PACU stay,and postoperative hospitalization time were significantly shorter in multiparameter group(P＜0.05),the PSI was significantly increased 5,30,and 60 minutes after incision and at the end of surgery,and the SEF was significantly increased 5 minutes after induction of anesthesia,5,30,and 60 minutes after induction and the end of surgery(P＜0.05).Compared with single parameter group,inci-dence of intraoperative BS was significantly decreased,duration of BS was significantly shorter,smaller maximum BSR was significantly decreased,and incidence of POD on 1 day after surgery in multiparameter group(P＜0.05).Conclusion Anesthesia management guided by multiparameter EEG can inhibit the oc-currence of BS,mitigate the degree of BS,and reduce the incidence of POD in elderly patients undergoing abdominal surgery.

Objective:Previous studies have revealed a correlation between eosinophils and allergic rhinitis,but the causal relationship has not been fully confirmed.This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization(MR)method. Methods:Summary data from the Genome-Wide Association Study Catalog(GWAS)for eosinophil count(exposure variable)and allergic rhinitis(outcome variable)were collected.GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol,while data for the outcome variable were sourced from the FinnGen Biobank(Finland)database.The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted(IVW)analysis.Sensitivity analyses were conducted using the weighted median method,MR-Egger regression,leave-one-out analysis,and funnel plots. Results:An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis(OR=1.187,95%CI 1.051 to 1.341,P=0.006).This finding was consistent across the weighted median method and MR-Egger regression.Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference. Conclusion:There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.

This paper analyzed the "non-standardization" phenomenon of syndrome differentiation in traditional Chinese medicine （TCM） from the diagnosis process. It is proposed that the symptoms and signs collected by the four examinations of inspection， listening/smelling， inquiry， and palpation naturally have a certain "ambiguity"， which can be reduced by the comparison and comprehensive condensation （comprehensive analysis of the four examinations） of a large amount of multi-dimensional clinical data， thereby realizing the sublimation of TCM diagnosis from "ambiguity" of four examinations to "accuracy" of diagnostic conclusion. Based on the above assumptions， this paper further proposed that a research idea of intelligent syndrome differentiation in TCM， that is， by taking the clinical thinking ability of TCM physicians as the core， adopting artificial intelligence technology based on knowledge graph visualization， integrating the complex network association and reasoning method of "symptom-pathogenesis-syndrome" linked by pathogenesis， and through the automatic analysis and reasoning process of a large amount of multi-dimensional and ambiguous clinical data， the intelligent TCM diagnosis based on syndrome differentiation can be realized.

Objective:To explore the role and mechanism of miR-485-5p targeted regulation of WNT7B in regulating osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC). Methods:15 osteoporotic patients who underwent hip replacement due to hip fracture in Tianjin Hospital from January to October 2023 were collected, and bone tissues in the femoral head in the area of reduced bone density detected by the dual-energy X-ray absorptiometry (DXA) method were collected (osteoporosis group); 15 patients who underwent joint replacement due to osteoarthritis were matched according to their age and body mass index, and bone tissues in the femoral head in the area of normal bone density were collected (no osteoporosis group). MiR-485-5p and WNT7B were detected using qRT-PCR technology; the target genes and potential mechanisms of miR-485-5p were predicted using bioinformatics technology, and the relationship between miR-485-5p and WNT7B was analyzed by dual luciferase reporter system. The miR-485-5p overexpression (mimic) and inhibitor (inhibitor) were constructed and divided into control, miR-485-5p group and miR-485-5p inhibitor group. After alkaline phosphatase staining (ALP) and alizarin red staining (ARS), osteogenesis-related proteins were detected by Western blot (ALP, BMP-2, Runx2, OPN, OCN); expression of osteogenic proteins was detected by transfection of miR-485-5p inhibitor and WNT7B siRNA into BMSC. Results:The relative expression of miR-485-5p in the osteoporosis group was 7.54±0.49, which was higher than that in the no-osteoporosis group with significant difference ( t=4.11, P<0.001), while the relative expression of WNT7B was significantly lower ( t=3.38, P<0.001), which was negatively correlated with miR-485-5p; bioinformatics analysis found that miR-485-5p targeted 666 genes, miR-485-5p could bind the 3'UTR of WNT7B, and the main mechanism was related to the Wnt/β-catenin signaling pathway; ALP activity and calcium deposition were reduced in the miR-485-5p group compared with the control group, and ALP, BMP-2, Runx2, OPN, OCN, WNT7B and β-catenin proteins were 0.78±0.13, 0.68±0.16, 0.59±0.19, 0.54±0.14, 0.74±0.12, 0.49±0.17, 0.52±0.19, respectively, which were significantly reduced compared with the control group ( t=3.214, P<0.001; t=3.637, P<0.001; t=3.479, P<0.001; t=4.062, P<0.001; t=4.271, P<0.001; t=4.164, P<0.001; t=4.621, P<0.001), and ALP activity, calcium deposition were reduced; ALP, BMP-2, Runx2, OPN, OCN in miR-485-5p inhibition group, WNT7B and β-catenin protein relative expression were 1.29±0.21, 1.24±0.19, 1.16±0.24, 1.31±0.27, 1.45±0.25, 1.05±0.19, 1.41±0.26, respectively, which were significantly higher compared with the control group ( t=3.156, P<0.001; t=3.645, P<0.001; t=3.473, P<0.001; t=3.954, P<0.001; t=4.006, P<0.001; t=3.889, P<0.001; t=4.513, P<0.001). The relative expression of OPN, WNT7B and β-catenin proteins in the miR-485-5p inhibition group were 1.42±0.21, 1.38±0.32, 1.16±0.2.ALP activity was significantly lower in the miR-485-5p inhibition+WNT7Bi group, with lighter ARS staining, fewer bone deposits, and reduced bone-forming related proteins OPN, WNT7B and β-catenin relative expression of 1.08±0.19, 0.71±0.22, and 0.84±0.25, which were all significantly reduced ( t=3.675, P<0.001; t=3.401, P<0.001; t=3.354, P<0.001). Conclusion:MiR-485-5p overexpression slowed down the process of osteogenic differentiation and caused down-regulation of the expression of related proteins, whereas miR-485-5p inhibition promoted osteogenic differentiation and was negatively correlated with WNT7B in the bone tissues of osteoporosis patients. MiR-485-5p binds to the WNT7B mRNA target, which in turn influences the expression of related proteins of WNT7B, and the mechanism of its action is that miR-485-5p targeted to regulate WNT7B-mediated Wnt/β-catenin signalling pathway inhibits BMSC osteogenic differentiation.

Objective:To explore the common signaling pathways of Helicobacter pylori(Hp) infection and rosacea and screen Hub genes by bioinformatic analysis. Methods:Gene expression data sets related to Hp (GSE70394) and rosacea (GSE65914) were downloaded from GEO database. The common differentially expressed genes (DEGs) were screened by using the limma package of R and Venn diagram. Metascape database was used for gene ontology(GO) enrichment analysis, and clusterProfiler package of R was used for Kyoto encyclopedia of genes and genomes(KEGG) analysis on up-regulated and down-regulated genes. Subsequently, STRING and Cytoscape software were used to establish protein-protein interaction(PPI) network and its internal plug-in MCODE and Cytohubba were applied to screen key functional modules and Hub genes, then Hub genes were imported into GeneMANIA to construct Hub genes co-expression network. Finally, GO and KEGG enrichment analysis of Hub genes were performed again.Results:GSE70394 and GSE65914 data sets included three samples of AGS cells without Hp infection and three samples of AGS cells 24 hours after Hp infection, skin tissues from nineteen rosacea patients and ten healthy volunteers, respectively. Finally, 139 common DEGs were obtained including 93 up-regulated genes and 46 down-regulated genes. GO enrichment analysis mainly focused on smooth muscle cell regulation, vascular development and lipid metabolism. KEGG enrichment analysis mainly involved lipid and atherosclerosis, inflammatory response and immune-related pathways, such as PPAR signaling pathway, cytokine-cytokine receptor interaction, Th17 cell differentiation, IL-17 signaling pathway and NF-κB signaling pathway. Total of 16 Hub genes were identified by Cytohubba, including SPRR1B, GCLM, KRT16, GPX2, S100A2, SOD2, MMP1, MSMO1, HMOX1, GLRX, IL-1β, CXCL1, PPARγ, HMGCS1, SRXN1 and SPRR3.Conclusion:There is a link existing between Hp infection infection and rosacea. Hp may be involved in the occurrence and development of rosacea by mediating inflammatory immune response and regulating lipid metabolism, the selected Hub genes and related signaling pathways may provide a theoretical reference for subsequent correlation analysis.