BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

The enterotoxigenic Escherichia coli (ETEC) infection is a major factor restricting the development of animal husbandry. However, the abuse of antibiotics will lead to the antibiotic residues and emergence of antibiotic-resistant bacteria. The existing vaccines face challenges in stimulating intestinal immunity, demonstrating limited prevention effects. Therefore, it is indispensable to develop a new vaccine that is safe and suitable as a feed additive to activate intestinal immunity. This study constructed yeast-cell microcapsules (YCM) carrying the DNA vaccine against ETEC by genetic engineering. Furthermore, animal experiments were carried out to explore the regulatory effects of feeding YCM on the intestinal immune system and intestinal microbiota. Saccharomyces cerevisiae was selected as the oral delivery vehicle (microcapsules) of the DNA vaccine. The codon-optimized nucleic acid sequence of K88, the main antigen of mammal-derived ETEC, was synthesized, and the yeast shuttle vector containing the corresponding DNA vaccine expression cassette was constructed by DNA recombination. The recombinant strain of YCM was prepared by transforming JMY1. Additionally, the characteristics of the YCM strain and its feasibility as an oral vaccine were comprehensively evaluated by the fluorescence reporter assay, gastrointestinal fluid tolerance assay, intestinal epithelial cell adhesion assay, intestinal retention assessment, antiserum detection, and intestinal microbiota detection. The experimental results showed that the DNA vaccine expression cassette was expressed in mammals, and the recombinant strain of YCM could tolerate up to 8 hours of gastrointestinal fluid digestion and had good adhesion to intestinal epithelial cells. The results of mouse feeding experiments indicated that the recombinant strain of YCM could stay in the intestinal tract for at least two weeks, and the DNA vaccine expression cassette carried by YCM entered the intestinal immune system and triggered an immune response to induce the production of specific antibodies. Moreover, feeding YCM recombinant bacteria also improved the abundance of gut microbiota in mice, demonstrating a positive effect in regulating intestinal flora. In summary, we prepared the recombinant strain of YCM carrying the DNA vaccine against ETEC and comprehensively evaluated its characteristics and feasibility as an oral vaccine. Feeding the recombinant YCM could induce specific immune responses and regulate intestinal microbiota. The findings provide a reference for the immunoprevention of ETEC-related animal diseases.
Animals ; Enterotoxigenic Escherichia coli/genetics* ; Saccharomyces cerevisiae/metabolism* ; Vaccines, DNA/genetics* ; Mice ; Escherichia coli Infections/immunology* ; Escherichia coli Vaccines/genetics* ; Capsules ; Mice, Inbred BALB C ; Female

BACKGROUND:Studies have shown that chronic apical periodontitis is one of the common inflammatory bone destruction diseases.Icariin can promote osteogenic differentiation,inhibit bone resorption,and may play a protective role in bone destruction caused by chronic apical periodontitis. OBJECTIVE:To investigate the effect of icariin on the proliferation and differentiation of MC3T3-E1 cells in the inflammatory environment stimulated by lipopolysaccharides. METHODS:Lipopolysaccharides were used to stimulate MC3T3-E1 cells to establish an inflammatory environment in vitro,and cell counting kit-8 was used to detect the best concentration and optimal action time of lipopolysaccharides.Cell counting kit-8 was used to detect the optimal concentration of icariin under the stimulation of lipopolysaccharides at a concentration of 1 μg/mL.Alkaline phosphatase detection,Real-time PCR and western blot assay were used to detect the effect of icariin on osteogenic differentiation of MC3T3-E1 cells in the inflammatory environment.Real-time PCR and western blot were used to detect the effects of icariin on the expression of interleukin-1β and interleukin-6 in MC3T3-E1 cells in the lipopolysaccharide-stimulated inflammatory environment. RESULTS AND CONCLUSION:Cell counting kit-8 results showed that the optimal concentration of icariin was 0.1 μg/mL.In the inflammatory environment,icariin enhanced the expression of alkaline phosphatase and promoted osteoblast differentiation.Compared with the lipopolysaccharide group,the expression of osteogenesis-related factors alkaline phosphatase and Runx2 was increased in the lipopolysaccharide+icariin group.Compared with the lipopolysaccharide group,the expression levels of inflammation-related factors interleukin-1β and interleukin-6 decreased in the lipopolysaccharide+icariin group.To conclude,lipopolysaccharides weaken the osteogenic ability of MC3T3-E1 cells and aggravate the inflammatory response,but icariin has a protective effect on them.

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.