BACKGROUND:Mitochond rial dysfunction leads to cellular senescence and apoptosis,exacerbating tissue damage.Intercellular mitochondrial transfer in injured cells restores mitochondrial function,offering potential therapeutic strategies for mitochondria-related diseases.OBJECTIVE:To review the effects and regulatory mechanisms of intercellular mitochondrial transfer.METHODS:A comprehensive literature search was conducted on mitochondrial transfer between cells in the CNKI and PubMed databases from 2014 to 2024.The Chinese and English search terms used were"mitochondrial transfer,tunneling nanotubes,gap junctions,microvesicles,cell fusion."Eventually,a total of 74 articles were analyzed.RESULTS AND CONCLUSION:(1)The present review provides a comprehensive overview of the four principal mechanisms underlying mitochondrial transfer between cells,encompassing tunneling nanotubes,gap junctions,cell fusion,and microvesicles.(2)This article provides a comprehensive analysis of the pivotal roles played by intercellular mitochondrial transfer,encompassing material exchange,transmission of information,enhancement of host cell mitochondrial function,attenuation of oxidative stress,augmentation of cellular proliferation activity,anti-inflammatory effects,and anti-aging properties.(3)The article provides a comprehensive overview of the main regulatory mechanisms involved in cell mitochondria transfer.These include the promotion of tunneling nanotube formation and mitochondrial transfer by Miro 1,dependence of tunneling nanotubes-mediated mitochondrial transfer on host cell cyclic ADP ribose hydrolase expression,induction of tunneling nanotube formation in an oxidative stress environment,Ca2+-dependent gap junctions,influence of Cx43 on gap junction formation,contribution of Ras1 and actin activation to cell fusion,and involvement of actin and Rab6 in the regulation of mitochondrial exocytosis,activation of actin and NAD+-CD38-cADPR-Ca2+signaling pathways for promoting mitochondrial entry.(4)The transfer of mitochondria occurs via tunneling nanotubes,gap junctions,microvesicles,and cell fusion under the influence of cell signaling proteins,proteins associated with cellular dynamics,and oxidative stress.(5)Mitochondrial transfer plays a pivotal role in facilitating both material and information exchange between cells,thereby intimately linking to the onset and progression of diseases,which can provide new ideas for the treatment of mitochondria-related diseases.However,further investigations are warranted to unravel the effects and regulatory mechanisms of intercellular mitochondrial transfer.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

BACKGROUND:Mitochond rial dysfunction leads to cellular senescence and apoptosis,exacerbating tissue damage.Intercellular mitochondrial transfer in injured cells restores mitochondrial function,offering potential therapeutic strategies for mitochondria-related diseases.OBJECTIVE:To review the effects and regulatory mechanisms of intercellular mitochondrial transfer.METHODS:A comprehensive literature search was conducted on mitochondrial transfer between cells in the CNKI and PubMed databases from 2014 to 2024.The Chinese and English search terms used were"mitochondrial transfer,tunneling nanotubes,gap junctions,microvesicles,cell fusion."Eventually,a total of 74 articles were analyzed.RESULTS AND CONCLUSION:(1)The present review provides a comprehensive overview of the four principal mechanisms underlying mitochondrial transfer between cells,encompassing tunneling nanotubes,gap junctions,cell fusion,and microvesicles.(2)This article provides a comprehensive analysis of the pivotal roles played by intercellular mitochondrial transfer,encompassing material exchange,transmission of information,enhancement of host cell mitochondrial function,attenuation of oxidative stress,augmentation of cellular proliferation activity,anti-inflammatory effects,and anti-aging properties.(3)The article provides a comprehensive overview of the main regulatory mechanisms involved in cell mitochondria transfer.These include the promotion of tunneling nanotube formation and mitochondrial transfer by Miro 1,dependence of tunneling nanotubes-mediated mitochondrial transfer on host cell cyclic ADP ribose hydrolase expression,induction of tunneling nanotube formation in an oxidative stress environment,Ca2+-dependent gap junctions,influence of Cx43 on gap junction formation,contribution of Ras1 and actin activation to cell fusion,and involvement of actin and Rab6 in the regulation of mitochondrial exocytosis,activation of actin and NAD+-CD38-cADPR-Ca2+signaling pathways for promoting mitochondrial entry.(4)The transfer of mitochondria occurs via tunneling nanotubes,gap junctions,microvesicles,and cell fusion under the influence of cell signaling proteins,proteins associated with cellular dynamics,and oxidative stress.(5)Mitochondrial transfer plays a pivotal role in facilitating both material and information exchange between cells,thereby intimately linking to the onset and progression of diseases,which can provide new ideas for the treatment of mitochondria-related diseases.However,further investigations are warranted to unravel the effects and regulatory mechanisms of intercellular mitochondrial transfer.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

OBJECTIVES: To investigate the effect of recombinant human fibroblast growth factor 21 (rhFGF21) on the proliferation and mineralization of cementoblasts and its mechanism. METHODS: Hematoxylin eosin, immunohistochemical staining, and immunofluorescence were used to detect the expression and distribution of fibroblast growth factor 21 (FGF21) in rat periodontal tissues and cementoblasts (OCCM-30), separately. Cell Counting Kit-8 was used to detect the proliferation of OCCM-30 under treatment with rhFGF21. Alkaline phosphatase staining and Alizarin Red staining were used to detect the mineralization state of OCCM-30 after 3 and 7 days of mineralization induction. The transcription and protein expression of the osteogenic-related genes Runx2 and Osterix were detected by real-time quantitative polymerase chain reaction (PCR) and Western blot analysis. The expression levels of genes of transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling pathway in OCCM-30 were detected through PCR array analysis. RESULTS: FGF21 was expressed in rat periodontal tissues and OCCM-30. Although rhFGF21 had no significant effect on the proliferation of OCCM-30, treatment with 50 ng/mL rhFGF21 could promote the mineralization of OCCM-30 cells after 7 days of mineralization induction. The transcriptional levels of Runx2 and Osterix increased significantly at 3 days of mineralization induction and decreased at 5 days of mineralization induction. Western blot analysis showed that the protein expression levels of Runx2 and Osterix increased during mineralization induction. rhFGF21 up-regulated Bmpr1b protein expression in cells. CONCLUSIONS rhFGF21 can promote the mineralization ability of OCCM-30. This effect is related to the activation of the TGFβ/BMP signaling pathway.
Humans ; Rats ; Animals ; Dental Cementum ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Cell Differentiation ; Bone Morphogenetic Proteins/metabolism* ; Transforming Growth Factor beta/pharmacology*

ObjectiveTo observe the clinical efficacy of Qianghuo Shengshitang combined with ozone injection and radiofrequency thermocoagulation target puncture in the treatment of cervical spondylotic radiculopathy （wind-cold blockage type）. MethodSixty-eight patients with cervical spondylotic radiculopathy who were treated in Henan Province Hospital of Traditional Chinese Medicine from August 2020 to May 2021 were included and grouped into a control group and a research group by random number table， with 34 patients in each group. The control group was administrated with placebo granules of Qianghuo Shengshitang， and treated with ozone injection and radiofrequency thermocoagulation target puncture at the same time. The research group was given modified Qianghuo Shengshitang combined with ozone injection and radiofrequency thermocoagulation target puncture. Before and after treatment， patients in two groups were tested for the levels of tumor necrosis factor-α （TNF-α）， procalcitonin （PCT）， interleukin-2 （IL-2）， interleukin-1β （IL-1β）， 6-ketoprostaglandin E1α （6-keto-PGE1α）， plasma substance P （SP）， β-endorphin （β-EP）， lipid peroxide （LPO）， malondialdehyde （MDA）， and superoxide dismutase （SOD）. The pain visual scale （VAS）， cervical dysfunction index （NDI）， and clinical evaluation scale for cervical spondylosis （CASCS） were given to patients to evaluate the clinical efficacy. ResultCompared with those before treatment， the levels of IL-1β， PCT， and TNF-α in two groups were decreased， and the level of IL-2 was increased （P<0.05）. The improvement of IL-1β， PCT， TNF-α， and IL-2 was more obvious in the research group as compared with the control group （P<0.05）. After treatment， the levels of SOD in two groups were increased， while the levels of LPO and MDA were decreased （P<0.05）. After treatment， the improvement of SOD， LPO， and MDA was more obvious in the research group as compared with the control group （P<0.05）. Compared with those before treatment， the levels of SP and 6-keto-PGE1α in two groups were decreased after treatment， and the level of β-EP was increased （P<0.05）. The improvement of -keto-PGE1α and β-EP was more obvious in the research group as compared with the control group after treatment （P<0.05）. Compared with those before treatment， the VAS and NDI scores of the research group were decreased， and the CASCS scores were increased （P<0.05）. After treatment， the improvement of VAS， NDI， and CASCS of the research group was more obvious as compared with the control group （P<0.05）. After treatment， the total effective rate of patients in the research group was higher than that in the control group （Z=2.018， P<0.05）. ConclusionModified Qianghuo Shengshitang combined with ozone injection and radiofrequency thermocoagulation target puncture in the treatment of patients with cervical spondylotic radiculopathy （wind-cold blockage type） can inhibit inflammation， remove oxygen free radicals， improve the level of pain mediators， relieve pain， and improve cervical spine function and clinical efficacy.

Objective:To evaluate the effect of micro-implant assisted rapid palatal expansion (MARPE) in patients with different radiographic stages of midpalatal suture maturation.Methods:Twenty-eight patients [7 males and 21 females; age (15.5±5.5) years] with maxillary transverse deficiency were selected in the Department of Orthodontics, Hospital of Stomatology, Jilin University from February 2017 to October 2019. According to the fusion of the midpalatal suture, the patients were divided into two groups: 10 patients [3 males and 7 females; age (19.9±6.9) years] were in fusion group and 18 patients [4 males and 14 females; age (13.0±2.4) years] were in non-fusion group. Each patient had cone-beam CT (CBCT) images taken immediately after the placement of micro-implants (T1) and the completion of maxillary expansion (T2). The CBCT images were analyzed using the Dolphin Imaging software to evaluate the amount of midpalatal expansion and the percentages of bony expansion, etc. Statistical analysis was carried out to compare the two groups.Results:After MARPE treatment, the amount of sutural expansion in fusion group was (3.23±1.45) mm while that in non-fusion group was (4.97±1.47) mm ( P<0.05). There was a statistically significant difference in the percentages of bony expansion efficiency between the non-fusion group (71±20)% and the fusion group (46±18)% ( P<0.05). Conclusions:Bony expansion efficiency was affacted by the radiographic stages of midpalatal suture maturation.

Objective:To study the effects of combined occupational exposure of benzene, toluene, and xylene on human metabolism at an overall level, and to screen biomarkers related to the combined occupational exposure of benzene, toluene, and xylene, and to explore the mechanism of early health effects preliminarily caused by combined occupational exposure of benzene, toluene, and xylene by identification of biomarkers and retrieval of metabolic pathways.Methods:A shoe-making company was selected as the research site. Twenty subjects for the exposed group and the control group were selected separately, and urine of the subjects was collected. The metabolic profiles of the samples were collected by liquid chromatography time-of-flight mass spectrometry, and professional metabolomics and multivariate statistical analysis software were used to establish PCA and OPLS-DA analysis models to screen potential biomarkers and identify biomarkers. Finally, based on the dynamic changes and trends of potential biomarkers between groups, the mechanism of body damage caused by benzene, toluene, and xylene was initially explored.Results:Urine metabolomics analysis showed that the metabolic profile of urine samples of the benzene, toluene, and xylene combined exposure group was different from that of the control group. 27 potential biomarkers that were closely related to the combined exposure of benzene, toluene, and xylene were screened and identified. These potential biomarkers were enriched in 16 metabolic pathways, of which 3 pathways were significantly enriched ( P<0.05) , respectively, lysine metabolism, amino sugar metabolism, and nucleotide sugar metabolism. Conclusion:The metabonomics method can well reflect the changes in the metabolome of urine samples in the occupational population after the combined exposure of benzene, toluene, and xylene, which will help us better evaluate the risk of combined exposure of benzene, toluene, and xylene and prevent and control their health risks.