BACKGROUND:Chronic myofascial trigger points can identify differential metabolite changes through non targeted metabolomics techniques,helping to understand and further explore the pathophysiological processes and pathogenesis of chronic myofascial trigger points from the perspective of endogenous small molecule metabolites. OBJECTIVE:To investigate potential biomarkers and related metabolic pathways based on urine metabolomics in the rat model of chronic myofascial trigger points. METHODS:Sixteen Sprague-Dawley rats were randomly divided into a model group and a normal group.The model group was used to establish a chronic myofascial trigger point animal model by combining blunt hitting with centrifugal exercise(treadmill slope:-16°,running speed:16 m/min,training time:90 minutes each),once a week for 8 continuous weeks,with 4 weeks off.After 12 weeks of modeling,the metabolic cage method was used to collect urine from rats at 24 hours after modeling.Liquid chromatography-mass spectrometry non-targeted metabolomics technology was used to detect metabolic profiles in the urine samples,screen common differential metabolites,and conduct bioinformatics analysis. RESULTS AND CONCLUSION:Compared with the normal group,there were 32 differential metabolic markers in the model group,of which 21 were upregulated and 11 were downregulated.A total of 14 differential metabolites were identified as potential biomarkers based on the value of variable important in projection greater than 3.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes indicated that the formation of chronic myofascial trigger points is closely related to metabolic pathways such as primary bile acid biosynthesis and arachidonic acid metabolism.

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

The European Society of Endodontology published the S3-level clinical practice guideline for the treatment of pulpal and apical disease in October 2023, which provides best current therapeutic strategies supported by scientific evidences. The guideline was divided into four parts: the diagnosis and treatment of pulpitis, diagnosis and nonsurgical treatment of apical periodontitis, surgical treatment of apical periodontitis, and regenerative treatment. This article aims to introduce and interpret the guideline, and to better manage patients with pulpitis and apical periodontitis for preserving teeth over a patient′s lifetime in China.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.