OBJECTIVE:The optimal non-surgical therapy for chronic ankle instability remains unclear due to the continuous introduction of novel treatment methods despite the availability of several non-surgical options for improving foot and ankle function and dynamic balance in chronic ankle instability patients.This study aims to investigate the most effective non-surgical therapy options to improve foot and ankle function and dynamic balance for patients with chronic ankle instability using a network meta-analysis. METHODS:Using"CAI,exercise,and randomized controlled trial"as search terms,a literature search of PubMed,Embase,Cochrane Library,and Web of Science databases was conducted through a computer network to collect information from the databases from their inception to March 2024 on non-surgical therapies for the treatment of chronic ankle instability randomized controlled trials on foot and ankle function or dynamic balance in patients.EndNote software was utilized for literature management.RevMan 5.4 software and Cochrane Risk of Bias Assessment Tool were used to evaluate the risk of bias of the included literature.Paired meta-analysis and network meta-analysis of the outcomes such as the Foot and Ankle Ability Measure in daily living subscale score,Foot and Ankle Ability Measure in sports activities subscale score,Star Excursion Balance Test-Anterior score,Star Excursion Balance Test-Posteromedial score,Star Excursion Balance Test-Posterolateral score and Cumberland ankle instability tool score were performed using the network commands of Stata 14.0 software.The strength of evidence rating of the outcome metrics was evaluated according to the GRADE Level of Evidence and Strength of Recommendation Grading Criteria. RESULTS:Of the 22 randomized controlled trials that met the inclusion criteria,1 study was rated as low risk,8 studies were rated as medium risk,and 13 studies were rated as high risk,enrolling a total of 952 patients and 25 treatments.(1)Network meta-analysis showed that compared with the control group,Isokinetic Strength Training,Balance Training,Balance+Stroboscopic Glasses Training,Strength Training,Joint Mobilizations Training,CrossFit Training,CrossFit Training+Self-Mobilization,Wobble Board Training,National Academy of Sport Medicine corrective exercise program,Trigger Point Dry Needling,and Neuromuscular Training had different significant enhancement effects on improving foot and ankle function and dynamic balance in patients with chronic ankle instability(P<0.05).(2)Cumulative probability ranking results showed that the three treatments with the highest ranked Cumberland ankle instability tool score were Joint Mobilizations Training(88.6%)>Visual Feedback Balance Training(83.1%)>CrossFit Training+Self-Mobilization(74.8%);the three treatments with the highest ranked Star Excursion Balance Test-Anterior score were Joint Mobilizations Training(88.4%)>Isokinetic Strength Training(86.9%)>National Academy of Sport Medicine corrective exercise program(65.0%);the three treatments with the highest ranked Star Excursion Balance Test-Posteromedial score were Balance+Stroboscopic Glasses Training(87.4%)>Neuromuscular Training(74.6%)>Strength Training(68.9%);the three treatments with the highest ranked Star Excursion Balance Test-Posterolateral score were CrossFit Training+Self-Mobilization(74.6%)>Balance+Stroboscopic Glasses Training(70.0%)>Neuromuscular Training(63.7%);the three treatments with the highest ranked Foot and Ankle Ability Measure in daily living subscale score were National Academy of Sport Medicine corrective exercise program(91.9%)>Balance+Stroboscopic Glasses Training(85.6%)>Wobble Board Training(82.2%);the three treatments with the highest ranked Foot and Ankle Ability Measure in sports activities subscale score were Balance+Stroboscopic Glasses Training(93.5%)>Balance Training(86.7%)>National Academy of Sport Medicine corrective exercise program(86.4%). CONCLUSION:Non-surgical therapies can significantly improve foot and ankle function and dynamic balance in patients with chronic ankle instability.National Academy of Sport Medicine corrective exercise program had the best efficacy in improving foot and ankle daily activity function in chronic ankle instability patients;Balance+Stroboscopic Glasses Training had the best efficacy in improving foot and ankle sports function and posterior medial dynamic balance;Joint Mobilizations Training had the best efficacy in improving anterolateral dynamic balance and ankle instability condition;and CrossFit Training+Self-Mobilization had the best efficacy in improving posterior lateral dynamic balance.The strength of evidence for each outcome was low,influenced by the risk of methodological bias and risk of publication bias of the included studies.Therefore,the above conclusions need to be validated by more high-quality pilot studies.
BACKGROUND:Sarcopenia is a comprehensive condition of aging induced decline in skeletal muscle mass and strength and represents a major health challenge for the elderly.Accumulating evidence suggests that mitochondrial dysfunction plays a key role in the pathogenesis of sarcopenia. OBJECTIVE:To summarize the mechanisms by which dysregulation of mitochondrial quality control leads to sarcopenia and to explore whether mitochondrial transplantation may be a potential target for the treatment of sarcopenia. METHODS:We searched PubMed and CNKI databases for relevant articles published from 2009 to 2023 using the keywords "sarcopenia,mitochondrial dysfunction,mitochondrial quality control,mitochondrial transplantation,limitations." RESULTS AND CONCLUSION:Given the key role of mitochondrial dysfunction in the pathogenesis of sarcopenia,mitochondrial transplantation may serve as a possible strategy for the treatment of sarcopenia by improving mitochondrial bioenergetics and modulating mitochondria related signaling pathways.Although some preclinical and clinical studies have confirmed the potential of mitochondrial transplantation for the treatment of various diseases,there are still some urgent questions regarding the specific details of mitochondrial transfer.
The effect of circumference and displacement of the third fracture fragment on fracture healing after intramedullary nailing of femoral shaft fractures with a third fracture fragment was investigated. A retrospective cohort study was conducted to analyze the data of 142 patients who suffered femoral shaft fractures with a third fracture fragment and were admitted to the First People’s Hospital of Lianyungang from February 2016 to December 2021. According to the circumference of the third fracture fragments, these were divided into three types of type 1: 71 cases; type 2: 52 cases; and type 3: 19 cases. On the basis of the diaphyseal diameter, the degree of displacement of the third fracture fragment was classified into three degrees of degree I: 95 cases; degree II: 31 cases; and degree III: 16 cases. Postoperative follow-up was performed to compare the fracture healing rate, healing time, and the modified Radiographic Union Scale for Tibia (mRUST) at 9th month after surgery in each group. All 142 patients were followed up after operation, with an average of (14.7 ± 4.1) months, and the overall healing rate was 73.4%. When the third fracture fragments were displaced in degree II and III, the mRUST score at 9th month in the type 1 group was higher than that in the type 2 and 3 groups (P = 0.017). Logistic regression analysis showed that greater displacement of third fracture fragments and greater circumference were associated with lower fracture healing rates (P < 0.05). After intramedullary nailing of femoral fractures, the degree of third fragment displacement and circumference affect fracture healing, and the former has a greater impact. When the third fracture fragment is displaced to degree II or III and its circumference is type 2 or type 3, it significantly affects the fracture healing. Intraoperative intervention to reduce the distance of third displacement of the fragment is required to reduce the incidence of non-union.
Three numerical methods, including element instantaneous failure, continuum damage mechanics, and extended finite element methods, are mainly used to simulate the fracture in cortical bone structure. Although many simulations focus on the cortical bone fracture, few have investigated the differences in prediction accuracy among the three numerical methods. The purpose of this study was to evaluate the prediction accuracy and applicability of the three numerical methods in simulating cortical bone fracture under bending load. The rat femur samples were first used to perform the three-point bending experiment. Then, the three numerical methods were respectively used to conduct fracture simulation on the femoral finite element models. Each result was compared with the experimental data to determine the prediction accuracy. The results showed that fracture simulation based on the continuum damage mechanics method was in better agreement with the experimental results, and observable differences in the failure processes could be seen in the same model under the three simulations due to various element failure strategies. The numerical method that was suitable for simulating cortical bone fracture under bending load was determined; meanwhile, the variations in the failure simulations were observed, and the cause of the variations in the predicted results using different numerical methods was also discussed, which may have potential to improve the prediction accuracy of cortical bone fracture.
OBJECTIVE:At present,there are various surgical repair strategies for the lateral stability of chronic ankle instability after the injury of the lateral collateral ligament of the ankle,but the specific repair strategy to maximize the recovery of lateral stability of the ankle still lacks of evidence-based medical evidence.Based on this,for the first time,this paper systematically evaluated the effects of four popular repair strategies to restore the lateral stability of chronic ankle instability using the network meta-analysis method. METHODS:Computer retrieval was conducted on CNKI,WanFang,VIP,PubMed,Embase,Web of Science and Cochrane Library.The retrieval time was from the establishment of each database to December 2022.The randomized controlled trials or clinical controlled trials on different repair strategies to recover chronic ankle instability after injury of the lateral ligament of the ankle were included.The literature was screened and extracted.The literature quality was evaluated and data were analyzed using RevMan 5.4,R4.2 and Stata 14.2 software. RESULTS:Twelve studies(including 10 randomized controlled trials and 2 cohort studies)were included.A total of 673 patients with chronic ankle instability were involved in 4 repair strategies.The observation indicators were:anterior talar translation distance and talar tilt angle of ankle joint stress X-ray film(hereinafter referred to as anterior talar translation distance and talar tilt angle).The results of network meta-analysis showed that:(1)In terms of anterior talar translation distance,the sequence of reticular meta-analysis results from inferior to superior was anatomical repair>anatomical repair + enhancement of inferior extensor retinaculum>internal brake anatomical reconstruction>autologous/allogeneic tendon anatomical reconstruction.(2)In terms of talar tilt angle,the sorting results of reticular meta-analysis from inferior to superior were as follows:anatomical repair>anatomical repair + inferior extensor retinaculum enhancement>internal brace anatomical reconstruction>autologous/allogeneic tendon anatomical reconstruction. CONCLUSION:Anatomical reconstruction strategy of autologous/allogeneic tendon is the first in improving anterior talar translation distance and talar tilt angle,suggesting that this strategy may have the best effect in restoring the stability of chronic joint instability after injury of the lateral ligament of ankle,but more large sample,multicenter,double-blind randomized controlled trials are still needed in the future to further confirm.
BACKGROUND:Cellular senescence is closely related to the development and progression of osteoarthritis,but the specific targets and regulatory mechanisms are not yet clear. OBJECTIVE:To mine key genes in cellular senescence-mediated osteoarthritis by integrating bioinformatics and machine learning approaches and validate them via experiments to explore the role of cellular senescence in osteoarthritis. METHODS:The osteoarthritis gene expression profiles obtained from the GEO database were intersected with cellular senescence-related genes obtained from the CellAge database and the expression of the intersected genes was extracted for differential analysis,followed by GO and KEGG analysis of the differential genes.The key osteoarthritis cellular senescence genes were then screened by protein-protein interaction network analysis and machine learning,and in vitro cellular experiments were performed.Finally,the expression of the key genes was detected by qPCR. RESULTS AND CONCLUSION:A total of 31 osteoarthritis cell senescence differential genes were identified.GO analysis showed that these genes were mainly involved in the biological processes,such as regulation of leukocyte differentiation,monocyte differentiation,regulation of T cell differentiation and exerted roles in DNA transcription factor binding,histone deacetylase binding,chromatin DNA binding,and chemokine binding.KEGG analysis showed that osteoarthritis cell senescence differential genes were mainly activated in the JAK/STAT signaling pathway,PI3K/Akt signaling pathway and FoxO signaling pathway.MYC,a key gene for osteoarthritis cellular senescence,was identified by protein-protein interaction network topology analysis and machine learning methods.The results of the in vitro cellular assay showed that the mRNA expression of MYC was significantly lower in the experimental group(osteoarthritis group)than the control group(normal group)(P＜0.05).To conclude,MYC can be a key gene in the senescence of osteoarthritic cells and may be a new target in the prevention and treatment of osteoarthritis by mediating immune response,inflammatory response and transcriptional regulation.
BACKGROUND:Superovulation is a common therapy in assisted reproductive technology.In clinical practice,some patients experience repeated superovulation to get pregnant. OBJECTIVE:To explore the effect of repeated superovulation on the developmental potential of oocytes in mice and humans. METHODS:Both animal experiments and retrospective clinical research were conducted.The animal study involved 90 SPF grade ICR 8-week-old female mice,who were randomly divided into three groups for 1,3,and 5 superovulations,respectively.The clinical study involved 306 patients who had undergone three consecutive in vitro fertilization cycles.The number of ovules obtained and embryonic development in different cycles were compared. RESULTS AND CONCLUSION:(1)The animal study indicated that repeated superovulation did not affect the embryonic development or developmental speed of mouse embryos.Similarly,there was no significant difference in the mouse blastocyst apoptosis,DNA damage,or the formation of inner cell mass and trophectoderm(P>0.05).(2)The clinical study also revealed no significant differences in the number of retrieved oocytes(8.60±5.04,8.58±4.87,and 8.38±4.63,P=0.81)and transferable embryos(2.42±1.99,2.40±1.92,and 2.64±2.00,P=0.26)over the three cycles.(3)In both the young group(<35 years)and the old group(≥35 years),the embryo quality was not affected by repeated superovulation(P>0.05).(4)These findings show that repeated superovulation does not affect the developmental potential of oocytes in mice and humans.
BACKGROUND:Oxidative modification of high-density lipoprotein occurs in patients with polycystic ovary syndrome.However,the relationship between oxidized high-density lipoprotein and ovulation dysfunction and its mechanism are unknown. OBJECTIVE:To investigate the effect and potential mechanism of oxidized high-density lipoprotein on ovarian granulosa cell apoptosis. METHODS:Polycystic ovary syndrome rat model was established,then the high-density lipoprotein was harvested from the rat serum of heart blood.The degree of oxidation of the high-density lipoprotein was detected by high-density lipoprotein inflammation index assay,malondialdehyde assay and lipoprotein agarose gel electrophoresis assay.The normal rat ovarian granulosa cells were isolated and treated with high-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum.Cell viability was detected by CCK-8 assay.Cell apoptosis was detected by flow cytometry.The generation of reactive oxygen species was detected by H2DCF-DA staining.The p38 signaling activity was detected by western blot assay.Ovarian granulosa cells were pretreated with reactive oxygen species inhibitors N-acetylcysteine,tetramethylpiperidine(Tempol)and p38 inhibitor SB203580,and then treated with oxidized high-density lipoprotein.Finally,cell apoptosis,reactive oxygen species production and p38 signaling activity were detected. RESULTS AND CONCLUSION:A portion of the high-density lipoprotein from the serum of polycystic ovary syndrome model rats affected oxidative modification.High-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum inhibited granulosa cell viability and promoted apoptosis(all P<0.05).They promoted rat granulosa cell reactive oxygen species production and p38 activation(all P<0.05).N-acetylcysteine,Tempol and SB203580 reversed oxidized high-density lipoprotein induced granulosa cell apoptosis(all P<0.05).N-acetylcysteine and Tempol suppressed oxidized high-density lipoprotein-induced p38 activation(all P<0.05).SB203580 did not have a regulatory effect on reactive oxygen species production(P>0.05).In summary,polycystic ovary syndrome can promote partial oxidative modification of high-density lipoprotein.The oxidized high-density lipoprotein promotes rat granulosa cell apoptosis by the activation of the reactive oxygen species-initiated p38 signaling pathway.
BACKGROUND:Bone marrow mesenchymal stem cells have been widely used to treat neurological diseases.However,due to limitations of the blood-brain barrier,low survival rate and differentiation rate of stem cells at damaged sites,the therapeutic effect is limited. OBJECTIVE:To investigate the effects of Shexiang Huangqi compound dripping pills on proliferation,migration and astrocyte differentiation of bone marrow mesenchymal stem cells. METHODS:Male SD rats were treated with Shexiang Huangqi compound dripping pills for 5 days after continuous gavage.Blood was collected from the abdominal aorta and serum was separated for later use.The effect of 5%,10%and 20%drug-containing serum on the proliferation of bone marrow mesenchymal stem cells was detected by CCK-8 assay.The effect of 10%drug-containing serum on lateral migration of bone marrow mesenchymal stem cells was observed by scratch test.Bone marrow mesenchymal stem cells were cultured in Transwell cells.The effects of 10%drug-containing serum on longitudinal migration of bone marrow mesenchymal stem cells were observed by crystal violet staining and DAPI nuclear staining.Differentiation of bone marrow mesenchymal stem cells into astrocytes was observed by inducing solution with 10%drug-containing serum or co-culture with astrocytes. RESULTS AND CONCLUSION:(1)10%and 20%drug-containing serum promoted cell proliferation more significantly on days 2 and 3,and there was no statistical difference between the two concentrations.(2)At 30 and 48 hours,bone marrow mesenchymal stem cell migration in 10%drug-containing serum group was significantly higher than that in the control group.(3)The number of bone marrow mesenchymal stem cells filtered through Transwell cells in 10%drug-containing serum group was higher than that in the control group.(4)10%drug-containing serum might promote the differentiation of bone marrow mesenchymal stem cells to astrocytes,but the differentiation effect was weak,and astrocytes might further promote the differentiation of bone marrow mesenchymal stem cells into astrocytes induced by drug-containing serum.(5)The results exhibited that the 10%drug-containing serum could promote the proliferation and migration of bone marrow mesenchymal stem cells in vitro.Co-culture with astrocytes may promote the differentiation of bone marrow mesenchymal stem cells towards astrocytes.
BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.
BACKGROUND:Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury.3-Nitro-N-methylsalicylamide(3-NNMS)can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury,but there is no clear research and clinical application. OBJECTIVE:To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS:Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group,0,25 and 125 μg/mL 3-NNMS groups,with 10 rats in each group.Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups.3-NNMS was injected into the injury site 30 minutes before reperfusion.The animals were sacrificed 2 hours after reperfusion.Blood from the apical part of the heart,and the tissue of the rectus femoris muscle of the right lower limb were taken for testing.The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining.Serum levels of creatine kinase found in the skeletal muscle(CK-MM),lactate dehydrogenase,and myeloperoxidase were detected using ELISA;the levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde,reactive oxygen species,superoxide dismutase,catalase and glutathione peroxidase in the rectus femoris muscle were measured;and adenosine triphosphate(ATP)level,ATPase activity,and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION:Compared with the control group,the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase,increased levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle,and reduced ATPase activity and mitochondrial respiratory control rate.Moreover,cell morphology was irregular,inflammatory cell infiltration was obvious,and the cells were swollen in rats after ischemia-reperfusion injury.Compared with the 0 μg/mL group,the serum CK-MM and lactate dehydrogenase levels decreased,the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased,reactive oxygen species level decreased,and superoxide dismutase activity increased in the 25 μg/mL group;cell morphology was more regular,inflammatory cell infiltration was lighter,and cell swelling was alleviated.Compared with the 0 μg/mL group,the 125 μg/mL group had a reduction in the serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase and the levels of nuclear factor κB,tumor necrosis factor α,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle,and mitochondrial respiratory control rate.Moreover,the cells were arranged neatly,the outline was clear and complete,and the inflammatory cell infiltration was light.To conclude,3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion,and its mechanism of action may be through improving mitochondrial function,reducing reactive oxygen species production,decreasing oxidative stress and inflammatory response,and thus reducing tissue damage and repairing skeletal muscle function.
数字医学是一门计算机科学、信息学、电子学等与医学相互交叉的学科,研究的是将数字技术、信息技术、计算机技术、通信技术、人工智能技术、虚拟现实等技术作为工具应用于人类健康状况诊断、干预以及监控等医学领域中.
BACKGROUND:Mesenchymal stem cells are pluripotent stromal cells isolated from a variety of tissues,which can differentiate into osteoblasts under certain conditions.Photobiomodulation,as an external stimulus,can promote osteogenic differentiation combined with other inducers or alone,providing new ideas for solving a series of bone diseases. OBJECTIVE:To review the relevant literature and mechanisms of photobiomodulation-induced osteogenic differentiation of mesenchymal stem cells,which will lay a theoretical foundation for bone tissue engineering using mesenchymal stem cells as seed cells and may offer some suggestions for future studies. METHODS:Relevant articles were searched on CNKI,PubMed and Wed of Science databases with Chinese search terms of"photobiomodulation,low power laser,low level laser,light-emitting diode,mesenchymal stem cells,osteogenic differentiation,biomaterials"and English search terms of"photobiomodulation,low level laser(light),light-emitting diode(LED),mesenchymal stem cell,osteogenic differentiation,biomaterials".Finally,88 articles were included for analysis. RESULTS AND CONCLUSION:(1)Photobiomodulation represented by low level laser and diode laser has a positive effect on promoting the proliferation and differentiation of mesenchymal stem cells.(2)Photobiomodulation can induce osteogenic differentiation of mesenchymal stem cells,whose feasibility has been verified in cell and animal experiments.On one hand,photobiomodulation can promote the expansion and differentiation of stem cells in vitro by activating related signaling pathways and up-regulating the expression of osteogenic molecules.On the other hand,photobiomodulation can improve the survival rate of stem cells in vivo,promote homing effect and shorten the healing time of bone defects after stem cells are injected into the body.However,photobiomodulation has a biphasic dose effect,whose laser parameters,experimental environment,cell type and other factors in various studies are different,making the research results lack consistency and difficult to apply in the clinic.(3)Combined with biological materials,other physical factors and drugs,photobiomodulation can also accelerate osteogenic differentiation.(4)In conclusion,photobiomodulation has been used increasingly widely in the medical field with its advantages of non-invasive,efficient and less-side reactions,and its role in bone tissue engineering has gradually become prominent,which provides a new method for the treatment of bone defects and related diseases.Further exploration should be focused on the standardized treatment parameters of photobiomodulation.
BACKGROUND:Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps.However,their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE:To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells,and provide a reference for its further theoretical research and clinical application. METHODS:Relevant documents included in CNKI,WanFang and PubMed were searched.The Chinese and English search terms were"mesenchymal stem cell,ischemia-reperfusion adjustment of skin flap,mesenchymal stem cells,stem cells,skin flap,ischemia-reperfusion injury,pretreatment,gene modification,biomaterial packaging,joint application".The relevant documents since 2007 were retrieved,and the documents with little relationship between the research content and the article theme,poor quality and outdated content were eliminated through reading the article,and finally 75 documents were included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can inhibit inflammatory reactions,resist oxidative stress and induce angiogenesis,which has great potential in the treatment of skin flap ischemia-reperfusion injury.(2)Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury,their shortcomings in treatment have limited their widespread clinical application.Through pre-treatment(cytokines,hypoxia,drugs,and other pre-treatment mesenchymal stem cells),gene-modified mesenchymal stem cells,biomaterial encapsulation of mesenchymal stem cells,as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods,can not only overcome the shortcomings of mesenchymal stem cells in treatment,but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury.(3)Therefore,further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury.
BACKGROUND:Grape seed extract has been shown to be effective in inhibiting the growth of androgen-dependent tumors(e.g.,breast cancer),and thus grape seed extract could theoretically inhibit epiphyseal closure induced by estrogen in late adolescence. OBJECTIVE:To screen the effects of grape seed extract on apoptosis of growth plate chondrocytes and epiphyseal closure in rats. METHODS:(1)In vitro experiment:Growth plate chondrocytes from rat large tibia and femur at logarithmic growth stage were obtained and cultured in groups:normal control group,model control group(adding 17β-estradiol to induce apoptosis),positive control group(adding letrozole and 17β-estradiol),grape seed extract group(adding 17β-estradiol and 10 µg/mL grape seed extract),Caspase-9 inhibitor group(adding 17β-estradiol and Caspase-9 inhibitor),Caspase-9 agonist group(adding 17β-estradiol and Caspase-9 agonist).Cell apoptosis was detected by flow cytometry after 48 hours of culture.(2)In vivo experiment:Thirty 3-month-old Sprague-Dawley rats were randomly divided into model control group,positive control group and low-,medium-and high-dose groups,with five rats in each group.All rats were injected subcutaneously with 17β-estradiol(3 times per week)to establish epiphyseal closure models,followed by intragastric administration of letrozole in positive control group and 0.05,0.2 and 0.8 g/kg grape seed extract in low-,medium-and high-dose groups,respectively,once a day until over 2/3 of the epiphyseal plate in the model control group was closed.The length of the tibia was then observed.Another 18 Sprague-Dawley rats were randomly divided into model control group,positive control group,and medium-dose group,with 6 rats in each group,treated as above for 1.5 continuous months.The expression of Caspase-9 protein in rat growth plate cartilage was detected by western blot. RESULTS AND CONCLUSION:(1)In vitro experiment:17β-estradiol could induce apoptosis in growth plate chondrocytes,and letrozole,grape seed extract,and caspase-9 inhibitors could all inhibit apoptosis in growth plate chondrocytes.(2)In vivo experiment:When more than 2/3 of the epiphyseal plate in the model control group was closed,the number of rats with epiphysis closure in the positive control and medium-dose groups was less than that in the model control group(P＜0.05),and the tibial length was longer than that in the model control group(P＜0.05),and the Caspase-9 protein expression in the tibial growth plate was lower than that in the model control group(P＜0.05).To conclude,the appropriate dose of grape seed extract can effectively inhibit the apoptosis of growth plate chondrocytes and delay epiphyseal closure,which has the potential to promote bone growth.
BACKGROUND:Studies have exhibited that inhibiting apoptosis caused by endoplasmic reticulum stress can save part of nerve function.Epigallocatechin-3-gallate can inhibit endoplasmic reticulum stress,but it has poor bioavailability and is difficult to penetrate the blood-brain barrier.In combination with exosomes targeting spinal cord repair and high-potency drug loading,theoretically,the combination of the two can play a greater role in spinal cord protection. OBJECTIVE:To investigate the effects of epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosomes on endoplasmic reticulum stress and neurological function in rats with spinal cord ischemia/reperfusion injury. METHODS:Fifty SD male rats were randomly divided into sham surgery group,model group,epigallocatechin-3-gallate group,exosome group,and combined treatment group,with 10 rats in each group.The spinal cord ischemia/reperfusion injury model was made in the other four groups except for the sham surgery group.Local injection of physiological saline,exosomes,epigallocatechin-3-gallate,epigallocatechin-3-gallate + bone marrow mesenchymal stem cell exosomes was performed 2 hours after surgery through a caudal vein.Neurological function scores were performed on 7,14 and 28 days after spinal cord injury.14 days after spinal cord injury,hematoxylin-eosin staining,Nissl staining,and immunofluorescence staining of endoplasmic reticulum stress markers such as ATF6 and GADD153 were performed in the spinal cord tissues. RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,neurological function scores of the model group,exosome group,epigallocatechin-3-gallate group and combined treatment group all decreased to different degrees.The neurological function score of combined treatment group was better than that of the epigallocatechin-3-gallate group,exosome group and model group 14 days after surgery(P<0.05).The neurological function score of the combined treatment group was better than that of the model group and epigallocatechin-3-gallate group 28 days after surgery(P<0.05).(2)Hematoxylin-eosin staining and Nissl staining displayed that the number of neurons in the model group decreased,with a large number of cavity necrosis and scar hyperplasia in the spinal cord injury area.The number of neurons and peripheral cavity necrosis improved to varying degrees in the epigallocatechin-3-gallate group,exosome group,and combined treatment group,with the most significant improvement in the combined treatment group.(3)The expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153:14 days postoperatively,the expression of GADD153 in the combined treatment group was lower than that in the model group and epigallocatechin-3-gallate group(P<0.05),and the expression of ATF6 in the combined treatment group was lower than that in the model group,exosome group,and epigallocatechin-3-gallate group(P<0.05).(4)These findings confirm that epigallocatechin-3-gallate combined with bone marrow mesenchymal stem cell exosome can enhance the neurological function in rats with spinal cord ischemia/reperfusionn injury,which may be associated with the inhibition of the expression of endoplasmic reticulum stress-related proteins ATF6 and GADD153.
BACKGROUND:Modification of food consistency and volume is a commonly used method of swallowing compensation in clinical practice.Dry swallowing is a commonly used method of evaluation.The hyoid muscles are very important in swallowing.The effects of dry swallowing and swallowing tasks of different consistencies and volumes on hyoid muscle activation levels are still unclear. OBJECTIVE:To explore the effects of simple dry swallowing and swallowing tasks of different consistencies and volumes on the hyoid muscles in healthy adults. METHODS:A total of 44 healthy adults were included from April to August 2019,including 19 males and 25 females,with an average age of(21.7±2.8)years.They randomly performed dry swallowing and swallowing tasks of different consistencies(the International Dysphagia Diet Standardisation Initiative(IDDSI)frame levels 0-4)and volumes(5,10,20 mL),and the surface electromyogram signals of the hyoid muscles during each swallowing task were recorded.After processing the raw surface electromyogram signals,the activation levels of the hyoid muscles were compared between dry swallowing and swallowing tasks of different consistency and volume. RESULTS AND CONCLUSION:The mean amplitude values of the suprahyoid muscles corresponding to swallowing tasks of 20 mL for levels 0-4,10 mL for level 3,and 5 mL for level 4 were higher than those of dry swallowing(P＜0.05).The mean amplitude values of the suprahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than those of the 5-mL swallowing tasks of the corresponding consistencies,except for level 3(P＜0.05).The mean amplitude values of the suprahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than those of the 10-mL swallowing tasks of the corresponding consistencies,except for levels 2 and 3(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to all swallowing tasks were higher than that of dry swallowing(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than that of the 5-and 10-mL swallowing tasks of the corresponding consistencies(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to the 10-mL swallowing tasks of different consistencies were higher than those of the 5-mL swallowing tasks of the corresponding consistencies,except for level 3(P＜0.05).To conclude,in healthy adults performing swallowing tasks of different volumes and consistencies,the level of activation of the hyoid muscles is less susceptible to IDDSI frame levels 0-4 consistency and more susceptible to volume.The higher volume indicates the higher activation level of the hyoid muscles.
BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip® Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.
BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.
BACKGROUND:The second heart field is crucial for the development of the embryonic heart.Abnormal development of the second heart field can result in multiple cardiac malformations.After Cx43 gene knockout,reduced formation and proliferation of cells of the second heart field can be observed,but the specific reason remains unclear. OBJECTIVE:(1)To determine whether β-catenin,Smo and Cx43 were co-expressed in the second heart field and the endoderm,we observed the expression patterns of these proteins.(2)To explore whether Cx43 interacts with the Wnt/β-catenin pathway or the Shh pathway in the development of the second heart field. METHODS:Serial paraffin sections of the mouse embryos at embryonic days 10-12 were selected for immunohistochemical staining,hematoxylin-eosin staining and immunofluorescence staining.The primitive gut of mouse embryos at embryonic day 11 was separated for western blot assay and co-immunoprecipitation. RESULTS AND CONCLUSION:(1)Cx43 and Isl1 were co-expressed in some mesenchymal cells on the ventral side of the foregut and dorsal wall of the pericardial cavity of mouse embryos at embryonic days 10-12;Isl1 positive cells increased while Cx43 positive cells increased.(2)Cx43 and β-catenin were co-expressed in the ventral part of the endoderm at embryonic days 10-12.(3)Cx43 and Smo were co-expressed in the endoderm at embryonic days 10-12.(4)The co-immunoprecipitation results confirmed that there was an interaction between Cx43 and β-catenin,which suggested that Cx43 interacted with β-catenin to participate in the development of the second heart field.
