BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Objective:To investigate the factors affecting the efficacy of 131I treatment for Graves′ disease (GD) and to construct a predictive model for the treatment outcomes of 131I therapy. Methods:Retrospective analysis of the treatment efficacy was performed on 2 190 patients (547 males, 1 643 females, age (42.9±12.4) years) with GD, who received initial 131I treatment in Tianjin Medical University General Hospital between October 2013 and May 2018. Univariate analysis ( χ2 test, et al) and logistic regression were performed to analyze the possible factors affecting the efficacy of 131I treatment. An efficacy prediction model for 131I treatment of GD was constructed, and decision curve analysis (DCA) was used to evaluate the clinical utility of the prediction model. Results:The overall effectiveness rate of 131I treatment for GD patients was 99.95%(2 189/2 190), with a total cure rate of 83.74%(1 834/2 190), among which 94.11%(1 726/1 834) were cured after a single treatment. Pre-treatment thyroid mass was identified as an independent risk factor affecting the efficacy of initial 131I treatment (odds ratio ( OR)=0.983(95% CI: 0.977-0.989), P<0.001). The clinical cure rate was higher in patients who received an adequate dose of 131I compared with that in patients who didn′t receive an adequate dose (79.97%(1 537/1 922) vs 70.52%(189/268); χ2=12.57, P<0.001), but it did not increase the incidence of hypothyroidism within one year. A predictive model was constructed, and it was found that thyroid mass and disease duration had a relatively high impact on the clinical cure rate. The concordance index (C-index) of the predictive model was 0.623(95% CI: 0.593-0.654). DCA indicated that the predictive model offered substantial net benefits across a wide range of probability thresholds. Conclusions:131I treatment is effective in most patients with GD. The predictive model for efficacy of initial 131I treatment developed in this study can assist in evaluating treatment outcomes and help clinicians select the most suitable 131I treatment dose, enhancing clinical decision-making.

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

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: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

BACKGROUND:Lijin manipulation can reduce fibrosis scar hyperplasia and promote skeletal muscle repair.However,improper activation of the Wnt/β-catenin signaling pathway can aggravate the fibrosis of injured skeletal muscle and adversely affect the repair process of skeletal muscle.To study the regulatory effect of Lijin manipulation on the Wnt/β-catenin signaling pathway is conducive to elucidate the related mechanisms of Lijin manipulation in reducing fibrosis scar hyperplasia and promoting skeletal muscle injury repair.OBJECTIVE:To explore the mechanism of Lijin manipulation in promoting the repair of skeletal muscle injury in rabbits.METHODS:Forty-five healthy adult Japanese white rabbits were randomly divided into blank group,model group and Lijin group with 15 rabbits in each group.Gastrocnemius muscle percussion modeling was performed in both model group and Lijin group.Lijin manipulation was performed in the Lijin group on the 3rd day after modeling,once a day,15 minutes once.Five animals in each group were selected and killed on the 7th,14th and 21st days after modeling.The general morphological structure of gastrocnemius was observed by hematoxylin-eosin staining and the content of collagen fiber was observed by Masson staining.Western blot was used to detect the protein expression of Wnt3a,β-catenin,GSK3β,p-GSK3β,TCF,type I collagen and type III collagen in gastrocnemius muscle,and RT-PCR was used to detect the mRNA expression of Wnt3a,β-catenin and TCF.The expression of β-catenin was detected by immunofluorescence,and the expression of type I collagen and type III collagen was detected by immunohistochemistry.RESULTS AND CONCLUSION:The results of hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber amount decreased in the Lijin group(P<0.001),and muscle fibers gradually healed.Western blot results showed that compared with the model group,the protein expression levels of Wnt3a,β-catenin,TCF,type I collagen and type III collagen were significantly decreased in the Lijin group at all observation time points(P<0.05),while the ratio of P-GSK3β/GSK3β was significantly increased in the Lijin group at all observation time points compared with the model group(P<0.05).RT-PCR results showed that compared with the model group,the mRNA expression levels of Wnt3a,β-catenin and TCF were significantly decreased in the Lijin group at all observation time points(P<0.001).Immunofluorescence results showed that compared with the model group,the fluorescence intensity of β-catenin expression in the Lijin group was significantly decreased at each observation time point and gradually became similar to that in the blank group(P<0.001).Immunohistochemical results showed that the expression levels of type I collagen and type III collagen in the Lijin group were significantly lower than those in the model group(P<0.01).To conclude,Lijin manipulation could inhibit the abnormal activation of the Wnt/β-catenin signaling pathway,reduce fibrotic scar hyperplasia,and promote the repair of injured skeletal muscle.

BACKGROUND:Excessive apoptosis in skeletal muscle cells will destroy the dynamic balance of the number of myocytes,leading to pathological injury of skeletal muscle.Lijin manipulation is effective in treating skeletal muscle injury,but whether it can inhibit apoptosis and promote the repair of skeletal muscle injury is unknown.OBJECTIVE:To explore the mechanism by which Lijin manipulation reduces inflammation and apoptosis during the repair of skeletal muscle injury in rabbits.METHODS:Forty-five healthy adult Japanese white rabbits were randomly divided into blank group,model group and Lijin group(n=15 per group).No intervention was performed in the blank group.Gastrocnemius muscle percussion molding was performed in both the model group and Lijin group.After modeling,the model group was not treated,while the Lijin manipulation(Stroking,kneading,and rubbing)was performed in the Lijin group on the 3rd day,once a day,15 min/time.Sampling in each group was performed on the 7th,14th and 21st days after modeling.The general morphological structure of gastrocnemius was observed by hematoxylin-eosin staining.The ultrastructure of gastrocnemius muscle was observed by transmission electron microscopy.Apoptosis of gastrocnemius cells was observed by TUNEL staining.The expressions of interleukin-1β,interleukin-6 and interleukin-10 in gastrocnemius muscle were detected by ELISA.The protein expressions of BAX,BCL-2 and Caspase3 in gastrocnemius muscle were detected by western blot.The mRNA expression of BAX and BCL-2 was detected by RT-PCR.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results showed that compared with the model group,inflammatory cells decreased in number,myocyte amount increased,and muscle tissue gradually healed in the Lijin group at each observation point.(2)The results of transmission electron microscopy showed that compared with the model group,the arrangement of muscle fibers at each observation point in the Lijin group was gradually orderly,mitochondria were gradually complete,Z-line arrangement was gradually regular,and free ribosomes were gathered.(3)TUNEL staining results showed that compared with the model group,apoptosis rate in the Lijin group was gradually decreased at all observation points(P<0.05).(4)ELISA results showed that compared with the model group,the expression of interleukin-1β and interleukin-6 in the Lijin group continued to decrease(P<0.05),while the expression of interleukin-10 increased on the 7th day after modeling,and then showed a downward trend(P<0.05).(5)Western blot results showed that compared with the model group,the expression of BCL-2 protein/BAX protein in the Lijin group was significantly increased at each observational point(P<0.05).The protein expression of Caspase3 decreased significantly(P<0.001),and was gradually similar to that of the blank group.(6)RT-PCR results showed that compared with the model group,the mRNA expression level of BCL-2/BAX in the Lijin group was significantly higher at each observational point(P<0.05).To conclude,Lijin manipulation can inhibit inflammation,reduce apoptosis,and promote the repair of injured skeletal muscle.