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*

Objective:To explore the research status and hotspots of TCM syndrome differentiation and treatment for headache using bibliometrics.Methods:Literature about TCM syndrome differentiation and treatment for headache was retrieved from CNKI, VIP, Wanfang Data, and CBM from the establishment of the databases to July 18, 2024. Excel 2023 was used to extract information such as publication time, author, unit and keywords of the literature. The authors' affiliation and keywords were preprocessed. VOSviewer software was used for keyword co-occurrence analysis and clustering analysis, and a keyword temporal overlay network was constructed.Results:Totally 1 513 articles were finally included. The journal with the largest number of publications was Henan Traditional Chinese Medicine. 346 authors were involved, initially forming research teams represented with Cao Kegang, Zhou Jianwei, Ni Jinjun, etc., mainly from Beijing University of Chinese Medicine, Henan University of Chinese Medicine, Shandong University of Traditional Chinese Medicine, etc.; the included literature included a total of 2 153 keywords, which the frequency of 5 931 times in total. The top three keywords in frequency were acupuncture and moxibustion therapy, clinical efficacy, and experience of famous doctors. Current research hotspots included data mining, network pharmacology, literature research, syndrome elements, medication law, venturing and bloodletting therapy, calcitonin gene-related peptide, classic prescriptions, nitric oxide, etc. Conclusions:At present, research on TCM syndrome differentiation and treatment for headache mainly focuses on three major sections: acupuncture, moxibustion and massage, clinical efficacy of TCM syndrome differentiation and treatment, and experience of famous doctors. Future research mainly focuses on data mining, medication law, network pharmacology, syndrome elements, and pathogenesis.

Objective To study the mechanism by which acoustic wave stimulation improves cognitive function in sleep-deprived mice.Methods(1)Thirty-six male C57BL/6 mice were randomly divided into three groups:the control group,model group and acoustic wave group(n=12 per group).A sleep deprivation model was established using the modified multiple platform method.After 21 days of sleep deprivation in a row,mice in the acoustic wave group were exposed to 30-minute acoustic wave stimulation at 40 dB.(2)During sleep deprivation,the health status of each group of mice was recorded,including the mental state and body weight.(3)After 21 days of sleep deprivation,behavioral tests(open field test,novel object recognition test,Y-maze and Morris water maze)were performed to assess the spontaneous activity,spatial exploration,and such cognitive functions as learning and memory in mice.Immunohistochemistry was conducted to analyze the expressions of neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptor molecule 1(Iba-1)in the hippocampus.Quantitative real-time PCR(qPCR)was used to measure the expression levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and inducible nitric oxide synthase(iNOS)in the hippocampus.(4)Transcriptome sequencing was employed to explore the mechanism underlying the improvement of cognitive impairment by acoustic wave stimulation.Results After 21 days of sleep deprivation,acoustic wave stimulation significantly alleviated weight loss in mice(P＜0.01).The accuracy of Y-maze spontaneous alternation,indexes of novel object discrimination,the time spent in the target quadrant and the number of times the mice crossed the platformin the Morris water maze were all significantly increased(P＜0.05),while the escape latency was significantly reduced(P＜0.05).The average optical density of NeuN in the hippocampal CA3 region significantly increased(P＜0.05),GFAP and Iba-1 immunopositive cell counts significantly decreased(P＜0.01),and the mRNA levels of IL-6,TNF-α,and iNOS in the hippocampal tissue were significantly reduced(P＜0.05).Conclusion Acoustic wave stimulation can repair neural damage,modulate hippocampal inflammatory responses,and improve cognitive deficits induced by sleep deprivation.

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.

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.

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.

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.