BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

Objective To explore the effect of remote ischemic preconditioning (RIPC) on preoperative heart rate variability in patients with heart valves. Methods Patients scheduled to undergo on-pump cardiac valve surgery in the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, between January and July 2022 were initially enrolled. Eligible patients were randomly assigned at a 1 : 1 ratio to either the RIPC group or the control group. Relevant indicators of heart rate variability [standard deviation of NN interval (SDNN), standard deviation of mean value of NN interval in every five minutes (SDANN), mean square root of difference between consecutive NN intervals (RMSSD), percentage of adjacent RR interval>50 ms (PNN50), low frequency (LF) component, high frequency (HF) component and LF/HF] at 8 hours in the morning on the surgical day between two groups were compared. Results A total of 118 patients were initially assessed. After screening, 58 patients were excluded, and 60 patients provided written informed consent and were enrolled in the trial, with 30 allocated to the RIPC group and 30 to the control group. Seven patients in the control group and 5 patients in the RIPC group were subsequently excluded due to missing heart rate variability data resulting from cancelled operations. Finally, 23 patients in the control group and 25 patients in the RIPC group were included in the analysis. There was no statistical difference in baseline characteristics between the two groups, and there was no significant difference in heart rate variability 24 hours before intervention (P>0.05). After the intervention measures were taken, the comparison of the results of heart rate variability at 8 hours on the day of operation showed that SDNN and SDANN of patients in the RIPC group were higher than those in the control group, with statistical differences (P<0.05). Conclusion RIPC can stabilize the preoperative heart rate variability of patients undergoing cardiac valve surgery.

Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

Objective: To investigate the prognostic significance and biological functions of neutrophil extracellular traps (NETs) related genes in oral squamous cell carcinoma (OSCC). Methods: A total of 333 transcriptome datasets and 6 single-cell sequencing datasets of OSCC were retrieved from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Based on 69 NETs related gene sets, univariate Cox and Lasso-Cox regression were used to construct a prognostic risk model for OSCC. The model's efficacy was evaluated through Kaplan-Meier analysis and receiver operating characteristic (ROC) curves, and risk scoring and nomogram analysis were conducted. Further, the relationship between NETs risk scores and angiogenesis, epithelial-mesenchymal transition (EMT), and cell cycle was explored. Enrichment analysis was performed to annotate the functional characteristics of relevant pathways. Kaplan-Meier analysis was employed to screen for prognostic key genes. Candidate targets were validated through drug prediction and molecular docking assays. Single-cell RNA sequencing was utilized to characterize the expression profile of the key gene cathepsin G (CTSG) within the tumor microenvironment (TME). Using pan-cancer and OSCC related data retrieved from the TCGA database, we analyzed the differences in CTSG expression between tumor tissues and normal tissues. Subsequently, immunohistochemical staining experiments were performed on tissue microarrays to validate its expression at the protein level. Results: A prognostic risk model based on six NETs related genes (F3, AKT1, CTSG, VNN3, MPO, and IL17A) was successfully established. Patients in the high-risk group exhibited significantly shorter overall survival (OS) (P < 0.000 1). The area under the ROC curve (AUC) of the established model for predicting 1-, 3-, and 5-year overall survival (OS) rates was 0.718, 0.820, and 0.805, respectively. The NETs related risk score was identified as an independent prognostic factor (P < 0.001), with the constructed nomogram demonstrating good calibration. The NETs related risk score correlated with angiogenesis (r = ˗0.20,, P < 0.001), EMT (r = 0.17, P < 0.01), G1/S phase transition (r = 0.11, P < 0.05), and G2/M phase transition (r = 0.17, P < 0.01). GSEA（gene set enrichment analysis）revealed that the high-risk group was significantly enriched in pathways including basal cell carcinoma, whereas the low-risk group exhibited significant enrichment in pathways such as alpha-linolenic acid metabolism (P < 0.05). Kaplan-Meier analysis revealed that patients with low expression of CTSG had a poorer prognosis (P < 0.001). Molecular docking assays demonstrated a stable binding interaction between CTSG and glutathione (binding energy: -7.4 kcal/mol). Single-cell RNA sequencing analysis further showed that CTSG was highly expressed in mast cell subsets but weakly expressed in malignant cells (P < 0.001). TCGA pan-cancer analysis revealed that CTSG is underexpressed in multiple cancer tissues, including OSCC (P < 0.05). Immunohistochemical staining confirmed that CTSG protein expression was lower in tumor tissues than in paracancerous tissues (P < 0.01). Conclusion The NETs related prognostic model established in this study exhibits robust predictive performance. CTSG was identified as a key prognostic gene, thereby providing a novel biomarker and potential therapeutic target for prognostic evaluation and targeted therapy of OSCC.