BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
In this editorial,the authors of this paper comment on the article by Bokov et al published in the recent issue of World Journal of Orthopedics.We reviewed a general overview of oblique lumbar interbody fusions(OLIF)a...In this editorial,the authors of this paper comment on the article by Bokov et al published in the recent issue of World Journal of Orthopedics.We reviewed a general overview of oblique lumbar interbody fusions(OLIF)and lateral lumbar interbody fusions(LLIF),their indications and complications as an increasingly popular minimally invasive technique to address several lumbar pathologies.This editorial thoroughly discusses and reviews the literature regarding factors affecting outcomes of indirect decompression utilized through OLIF and LLIF procedures.Several parameters play a critical role in patient outcomes including restoration of disc height,foraminal height,central canal squared,and foraminal area.The indirect decompression allows for unbuckling of the ligamentum flavum which can significantly decompress the neural elements as well as aid in reduction of spondylolisthesis.However,the authors further highlight the limitations of indirect decompression and factors that may predict unsuccessful outcomes including bony foraminal stenosis,severe central canal stenosis,and osteoporosis.As a result,failure of indirect decompression can lead to persistent pain,radiculopathy and unsatisfied patients.Spinal surgeons may be left to reimage patients and consider additional procedures with direct decompression.展开更多
Interlayer heat accumulation(IHA)is major challenge in the laser powder bed fusion(LPBF)process,as it exacerbates the instability of melt pools,and compromises the quality of the as-built samples.Infrared radiation mo...Interlayer heat accumulation(IHA)is major challenge in the laser powder bed fusion(LPBF)process,as it exacerbates the instability of melt pools,and compromises the quality of the as-built samples.Infrared radiation monitoring is an effective method for exploring IHA.Based on the defined sequence features of interlayer infrared radiation intensity(IIRI),this study established a gated recurrent unit(GRU)neural network model for predicting IIRI in formed samples using machine learning to mitigate the IHA.The model trained on 316 L alloys achieved precise prediction results when transferred to the DZ125 superalloy,effectively managing various emergencies in the LPBF process.The truncated pyramid components were fabricated through parameter optimization based on IIRI prediction results.Compared with the non-optimized components,the CT results demonstrated a significant reduction in internal voids,with the relative density increasing from 91.6% to 98.5%.Additionally,surface roughness(Ra)decreased from 32.58μm to 19.91μm,while residual stress on the top surface was reduced from 169.21 MPa to 102.37 MPa.展开更多
Chromosomal evolution is widely considered an important driver of speciation because it can promote the establishment of reproductive barriers.Karyotypic reorganization is also expected to affect the mea n phe no type...Chromosomal evolution is widely considered an important driver of speciation because it can promote the establishment of reproductive barriers.Karyotypic reorganization is also expected to affect the mea n phe no type,as well as its developme nt and patter ns of phenotypic in tegrati on,through processes such as variation in genetic linkage between quantitative trait loci or between regulatory regions and their targets.Here we explore the relationship between chromosomal evolution and phenotypic integration by analyzing a well-known house mouse parapatric contact zone between a highly derived Robertsonian(Rb)race(2n=22)and populations with standard karyotype(2n=40).Populations with hybrid karyotypes are scattered throughout the hybrid zone connecting the two parental races.Using mandible shape data and geometric morphometries,we test the hypothesis that patter ns of in tegration progressively diverge from the"normal"integration pattern observed in the standard race as they accumulate Rb fusions.We find that the main pattern of integration observed between the posterior and anterior part of the mandible can be largely attributed to allometry.We find no support for a gradual increase in divergence from normal patterns of integration as fusions accumulate.Surprisingly,however,we find that the derived Rb race(2n=22)has a distinct allometric trajectory compared with the standard race.Our results suggest that either individual fusions disproportionately affect patterns of integration or that there are mechanisms which"purge"extreme variants in hybrids(e.g.reduced fitness of hybrid shape).展开更多
Tea infusion is the main route of human exposure to pollutants in tea,and it is vital to investigate the transfer rate of pollutants from tea leaves to infusion.Carbendazim is a commonly used systemic fungicide,the tr...Tea infusion is the main route of human exposure to pollutants in tea,and it is vital to investigate the transfer rate of pollutants from tea leaves to infusion.Carbendazim is a commonly used systemic fungicide,the transfer behavior of which in Yingshan Yunwu tea is not clear.Hence,this study firstly established the analytical method for determination of carbendazim with great accuracy and precision via modified QuEChERS method and ultra-performance liquid chromatography-fluorescence detection(UPLC-FLD).Then,the transfer behavior of carbendazim from tea leaves and infusion was systematically investigated.Results indicated that water temperature and proportion of tea to water ration would obviously increase the transfer rate of carbendazim,but times of infusion repetition showed negative correlation with the transfer rate of carbendazim.In addition,brewing time seemed to have lesser impact on the transfer rate.This study will be helpful for the risk assessment of carbendazim residue and provide the guidance for tea brewing.展开更多
Nowadays,cultural fusions and conflicts have become a hot issue.People do not know why they have so many influences,especially in the films’translations;the fusions and conflicts even have a new image.Follow some exp...Nowadays,cultural fusions and conflicts have become a hot issue.People do not know why they have so many influences,especially in the films’translations;the fusions and conflicts even have a new image.Follow some experts’footprints;I will analyze the cultural fusions and conflicts that appear in films’translations.As everyone knows,Assimilation and dissimilation are very common when we translate the lines.I will analyze a famous film,Kong Fu Panda,everyone likes films,so everyone in the world can feel this strong impact.To anyone who likes enjoying films,the translation of the lines can make a great difference on them.Films produced by foreign countries can be difficult to understand if the lines refer to some local cultures.From this point,how to deal with the cultural factors is a problem we meet.Generally speaking,as the same to other literary translations,the cultural factors in films’translations are difficult to control.To some degree,whether the understanding of the words is right or not is determined by one's knowledge of the relevant cultural factors.If the translators lack the comparable knowledge of different cultures,it is totally a blank to have a correct understanding and expression.展开更多
The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called g...The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.展开更多
Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-deriv...Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.展开更多
AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological character...AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(22)-DC. METHODS: DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR-,and were cultured in the medium containing GM-CSF and IL-4. A large number of DC were harvested. DCs were then fused with H(22) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(22)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(22)-DC in vitro. As the immunogen, H(22)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H22 cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(22)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(22)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(22) cells and its growth curve was flatter than H(22) cells. After subcutaneous inoculation over 60 days, H(22)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P【0.01). The spleen CTL activity against H(22) cells in mice implanted with fresh H(22)-DC was significantly higher than control groups (P 【 0.01). CONCLUSION: H(22)-DC could significantly stimulate the specific CTL activity of murine spleen, which suggests that the fusion cells have already obtained the function of antigen presenting of parental DC and could present H(22)specific antigen which has not been identified yet, and H(22)-DC could induce antitumor immune response; although simply mixed H(22) cells with DC could stimulate the specific CTL activity which could inhibit the growth of tumor in some degree, it could not prevent the generation of tumor. It shows that the DC vaccine is likely to become a helpful approach in immunotherapy of hepatocarcinoma.展开更多
This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activiti...This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm,and the protoplasts of C.militaris were inactivated by UV radiation to invalidate their genome function,then they were fused under optimal conditions to get a fusion rate as(7.42±0.8)×10^(-6) fusants/mL;the new fusants were abbreviated as Ac-Cm.On the other hand,when A.cinnamomea and C.militaris were treated with heat and UV oppositely using similar experiments,the fusion rate was(9.70±0.68)×10^(-5) fusants/mL,and the new fusants were abbreviated as Cm-Ac.We selected each of two best-growing fused colonies Ac-Cm-1,Ac-Cm-2,Cm-Ac-1,and Cm-Ac-2,together with parental A.cinnamomea and C.militaris,and studied their morphology,growth antagonism tests,and genetic relationships by 18 S rRNA sequencing.In comparison with the initial cultures of 4 fusants,the yields of adenosine,biomass,cordycepic acid,cordycepin,total polysaccharide,and total triterpenoids were increased up 1.305-50.1563 times in the optimal medium conditions.For gene stability tests,those of the four fusants and their outputs were stabilized within 10 generations.展开更多
Secretory carcinoma（SC）, previously described as mammary analogue secretory carcinoma（MASC）, is a recently described salivary gland tumor which morphologically resembles mammary secretory carcinoma. The first desc...Secretory carcinoma（SC）, previously described as mammary analogue secretory carcinoma（MASC）, is a recently described salivary gland tumor which morphologically resembles mammary secretory carcinoma. The first description of SC/MASC, reported by Skálová et al. in 2010, was as a rare salivary carcinoma imitating secretory carcinoma of the breast. SC/MASC is a unique salivary gland tumor with morphological overlap with acinic cell carcinoma（Aci CC）, mucoepidermoid carcinoma（MEC）, and adenocarcinoma not otherwise specified（ADCNOS）. SC/MASC shares similar clinicopathological features with Aci CC. As a critical difference between SC/MASC and Aci CC, SC/MASC characteristically has the chromosomal translocation t（12;15）（p13;q25） which leads to a fusion gene between the ETV6 gene on chromosome 12 and the NTRK3 gene on chromosome 15. This genetic background is an important differential diagnostic finding for excluding other salivary gland tumors and may be a critical factor determining the prognosis for patients with SC/MASC. Research in recent years has provided a large body of new data on SC/MASC and suggests the possibility that the ETV6-NTRK3 translocation could be a therapeutic target. Here, we review the morphological and clinicopathological features of SC/MASC and discuss new directions for therapy.展开更多
Objective： To investigate the immunotherapy efficacy of fusion cells （dendritic-C6anti-TGF-β1 cells） in the treatment of intraeranial gliomas. Methods： Dendritic cells were isolated from rat bone-marrow precursor...Objective： To investigate the immunotherapy efficacy of fusion cells （dendritic-C6anti-TGF-β1 cells） in the treatment of intraeranial gliomas. Methods： Dendritic cells were isolated from rat bone-marrow precursors stimulated in vitro with granuloeyte-macrophage colony-stimulating factor （GM-CSF） and Interleukin-4 （IL-4）. C6anti-TGF-β1 cells originally from C6 cell line of a rat glioblastoma were transfected with plasmid of TGF-β1 anti-sense gene. Fusions of dendritic cells and C6anti-TGF-β1 cells were prepared by polyethylene glycol （PEG）. The DC/C6anti-TGF-β1 fusion cells were observed and confirmed by fight microscopy and scanning electron microscopy. Experimental rats were divided into three groups at random： C6 cells （Ⅰ）, dendritic-C6anti-TGF-β1 fusion cells and C6 cells （Ⅱ） and IMDM medium only （Ⅲ）. The cells were injected into right parietal lobe region of the rat with stereotaxic technique. Histology, tumor necrosis and survival time were evaluated. Results： Compared with the rats that received C6 cells （survival median time was less than 20 days, tumor region was seen in all fields of observed）, the rats injected with dendritic-C6anti-TGF-β1 fusion cells and C6 cells got a more prolonged life span （more than 59 days）, as well as less tumor region （5.01%-6.2%）. There was no tumor necrosis, but some glias were seen in surroundings. All rats were survived and no necrosis was observed in negative control group. Statistical analysis showed that group Ⅱ had significant difference compared with group Ⅰ. Conclusions： Dendritic-C6anti-TGF-β1 fusion cells could prolong the life span of rats, providing a strategy to achieve an antitumor response against tumors in the central nervous system.展开更多
The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South Univers...The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).展开更多
In the standard fusion reactors, mainly tokamaks, the mechanical gain obtained is below 1. On the other hand, there are colliding beam fusion reactors, for which, the not neutral plasma and the space charge limit the ...In the standard fusion reactors, mainly tokamaks, the mechanical gain obtained is below 1. On the other hand, there are colliding beam fusion reactors, for which, the not neutral plasma and the space charge limit the number of fusions to a very small number. Consequently, the mechanical gain is extremely low. The proposed reactor is also a colliding beam fusion reactor, configured in Stellarator, using directed beams. D+/T+ ions are injected in opposition, with electrons, at high speeds, so as to form a neutral beam. All these particles turn in a magnetic loop in form of figure of “0” (“racetrack”). The plasma is initially non-thermal but, as expected, rapidly becomes thermal, so all states between non-thermal and thermal exist in this reactor. The main advantage of this reactor is that this plasma after having been brought up near to the optimum conditions for fusion (around 68 keV), is then maintained in this state, thanks to low energy non-thermal ions (≤15 keV). So the energetic cost is low and the mechanical gain (</span><i><span style="font-family:Verdana;">Q</span></i><span style="font-family:Verdana;">) is high (</span></span><span style="font-family:Verdana;">>></span><span style="font-family:Verdana;">1). The goal of this article is to study a different type of fusion reactor, its advantages (no net plasma current inside this reactor, so no disruptive instabilities and consequently a continuous working, a relatively simple way to control the reactor thanks to the particles injectors), and its drawbacks, using a simulator tool. The finding results are valuable for possible future fusion reactors able to generate massive energy in a cleaner and safer way than fission reactors.展开更多
Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detec...Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.展开更多
In a recent issue of The New England Journal of Medicine,an international team reported the final results of the Phase 2 eNRGy trial(NCT02912949),which evaluated the efficacy and safety of zenocutuzumab,a bispecific a...In a recent issue of The New England Journal of Medicine,an international team reported the final results of the Phase 2 eNRGy trial(NCT02912949),which evaluated the efficacy and safety of zenocutuzumab,a bispecific antibody against epidermal growth factor receptors 2 and 3(HER2 and HER3),in patients with Neuregulin 1(NRG1)fusion-positive solid tumors.1 The trial yielded compelling evidence of zenocutuzumab’s robust clinical efficacy in this molecularly defined population,accompanied by a favorable tolerability profile.展开更多
BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery...BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.展开更多
BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is ...BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is often recommended.We present a surgical technique that was successfully used on four such patients to convert them to a knee fusion(KF)using a cephalomedullary nail.CASE SUMMARY Four patients with infected long stem revision knee replacements that refused AKA had a single stage removal of their infected revision total knee followed by a KF.They were all treated with a statically locked antegrade cephalomedullary fusion nail,augmented with antibiotic impregnated bone cement.All patients had successful limb salvage and were ambulatory with assistive devices at the time of last follow-up.All were infection free at an average follow-up of 25.5 months(range 16-31).CONCLUSION Single stage cephalomedullary nailing can result in a successful KF in patients with infected long stem revision total knees.展开更多
Gastrointestinal tumors require personalized treatment strategies due to their heterogeneity and complexity.Multimodal artificial intelligence(AI)addresses this challenge by integrating diverse data sources-including ...Gastrointestinal tumors require personalized treatment strategies due to their heterogeneity and complexity.Multimodal artificial intelligence(AI)addresses this challenge by integrating diverse data sources-including computed tomography(CT),magnetic resonance imaging(MRI),endoscopic imaging,and genomic profiles-to enable intelligent decision-making for individualized therapy.This approach leverages AI algorithms to fuse imaging,endoscopic,and omics data,facilitating comprehensive characterization of tumor biology,prediction of treatment response,and optimization of therapeutic strategies.By combining CT and MRI for structural assessment,endoscopic data for real-time visual inspection,and genomic information for molecular profiling,multimodal AI enhances the accuracy of patient stratification and treatment personalization.The clinical implementation of this technology demonstrates potential for improving patient outcomes,advancing precision oncology,and supporting individualized care in gastrointestinal cancers.Ultimately,multimodal AI serves as a transformative tool in oncology,bridging data integration with clinical application to effectively tailor therapies.展开更多
Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.展开更多
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
文摘In this editorial,the authors of this paper comment on the article by Bokov et al published in the recent issue of World Journal of Orthopedics.We reviewed a general overview of oblique lumbar interbody fusions(OLIF)and lateral lumbar interbody fusions(LLIF),their indications and complications as an increasingly popular minimally invasive technique to address several lumbar pathologies.This editorial thoroughly discusses and reviews the literature regarding factors affecting outcomes of indirect decompression utilized through OLIF and LLIF procedures.Several parameters play a critical role in patient outcomes including restoration of disc height,foraminal height,central canal squared,and foraminal area.The indirect decompression allows for unbuckling of the ligamentum flavum which can significantly decompress the neural elements as well as aid in reduction of spondylolisthesis.However,the authors further highlight the limitations of indirect decompression and factors that may predict unsuccessful outcomes including bony foraminal stenosis,severe central canal stenosis,and osteoporosis.As a result,failure of indirect decompression can lead to persistent pain,radiculopathy and unsatisfied patients.Spinal surgeons may be left to reimage patients and consider additional procedures with direct decompression.
基金supported by National Natural Science Foundation of China(Grant No.52275333)the Key Research&Development Program of China Hubei Province(Grant No.2023BAB089).
文摘Interlayer heat accumulation(IHA)is major challenge in the laser powder bed fusion(LPBF)process,as it exacerbates the instability of melt pools,and compromises the quality of the as-built samples.Infrared radiation monitoring is an effective method for exploring IHA.Based on the defined sequence features of interlayer infrared radiation intensity(IIRI),this study established a gated recurrent unit(GRU)neural network model for predicting IIRI in formed samples using machine learning to mitigate the IHA.The model trained on 316 L alloys achieved precise prediction results when transferred to the DZ125 superalloy,effectively managing various emergencies in the LPBF process.The truncated pyramid components were fabricated through parameter optimization based on IIRI prediction results.Compared with the non-optimized components,the CT results demonstrated a significant reduction in internal voids,with the relative density increasing from 91.6% to 98.5%.Additionally,surface roughness(Ra)decreased from 32.58μm to 19.91μm,while residual stress on the top surface was reduced from 169.21 MPa to 102.37 MPa.
基金the Ministry of Scientific Research and Education,Italy(MIUR).
文摘Chromosomal evolution is widely considered an important driver of speciation because it can promote the establishment of reproductive barriers.Karyotypic reorganization is also expected to affect the mea n phe no type,as well as its developme nt and patter ns of phenotypic in tegrati on,through processes such as variation in genetic linkage between quantitative trait loci or between regulatory regions and their targets.Here we explore the relationship between chromosomal evolution and phenotypic integration by analyzing a well-known house mouse parapatric contact zone between a highly derived Robertsonian(Rb)race(2n=22)and populations with standard karyotype(2n=40).Populations with hybrid karyotypes are scattered throughout the hybrid zone connecting the two parental races.Using mandible shape data and geometric morphometries,we test the hypothesis that patter ns of in tegration progressively diverge from the"normal"integration pattern observed in the standard race as they accumulate Rb fusions.We find that the main pattern of integration observed between the posterior and anterior part of the mandible can be largely attributed to allometry.We find no support for a gradual increase in divergence from normal patterns of integration as fusions accumulate.Surprisingly,however,we find that the derived Rb race(2n=22)has a distinct allometric trajectory compared with the standard race.Our results suggest that either individual fusions disproportionately affect patterns of integration or that there are mechanisms which"purge"extreme variants in hybrids(e.g.reduced fitness of hybrid shape).
基金Supported by Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization,Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains Fund(2021CX06)Teaching and Research Project of Huanggang Normal University(2021CE20).
文摘Tea infusion is the main route of human exposure to pollutants in tea,and it is vital to investigate the transfer rate of pollutants from tea leaves to infusion.Carbendazim is a commonly used systemic fungicide,the transfer behavior of which in Yingshan Yunwu tea is not clear.Hence,this study firstly established the analytical method for determination of carbendazim with great accuracy and precision via modified QuEChERS method and ultra-performance liquid chromatography-fluorescence detection(UPLC-FLD).Then,the transfer behavior of carbendazim from tea leaves and infusion was systematically investigated.Results indicated that water temperature and proportion of tea to water ration would obviously increase the transfer rate of carbendazim,but times of infusion repetition showed negative correlation with the transfer rate of carbendazim.In addition,brewing time seemed to have lesser impact on the transfer rate.This study will be helpful for the risk assessment of carbendazim residue and provide the guidance for tea brewing.
文摘Nowadays,cultural fusions and conflicts have become a hot issue.People do not know why they have so many influences,especially in the films’translations;the fusions and conflicts even have a new image.Follow some experts’footprints;I will analyze the cultural fusions and conflicts that appear in films’translations.As everyone knows,Assimilation and dissimilation are very common when we translate the lines.I will analyze a famous film,Kong Fu Panda,everyone likes films,so everyone in the world can feel this strong impact.To anyone who likes enjoying films,the translation of the lines can make a great difference on them.Films produced by foreign countries can be difficult to understand if the lines refer to some local cultures.From this point,how to deal with the cultural factors is a problem we meet.Generally speaking,as the same to other literary translations,the cultural factors in films’translations are difficult to control.To some degree,whether the understanding of the words is right or not is determined by one's knowledge of the relevant cultural factors.If the translators lack the comparable knowledge of different cultures,it is totally a blank to have a correct understanding and expression.
基金supported by the following grants: National Natural Science Foundation of China No. 31571413, 31201037 (to Dr. Yu) and No. 81570180, 81072103 (to Dr. Wang) from the National Natural Science Foundation of China
文摘The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.
基金supported by the National Key Research&Development Program of China(Nos.2021YFC2302400,2021YFA1201000,2021YFE0106900)the National Natural Science Foundation of China(Nos.32171394,32101148,82202338)+2 种基金the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(No.20220484207)the Beijing Natural Science Foundation(No.L222128)the Fundamental Research Funds for the Central Universities(No.2022CX01013).
文摘Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.
基金Supported jby the Natural Science Foundation of Guangdong Province China,No.980180
文摘AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(22)-DC. METHODS: DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR-,and were cultured in the medium containing GM-CSF and IL-4. A large number of DC were harvested. DCs were then fused with H(22) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(22)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(22)-DC in vitro. As the immunogen, H(22)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H22 cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(22)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(22)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(22) cells and its growth curve was flatter than H(22) cells. After subcutaneous inoculation over 60 days, H(22)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P【0.01). The spleen CTL activity against H(22) cells in mice implanted with fresh H(22)-DC was significantly higher than control groups (P 【 0.01). CONCLUSION: H(22)-DC could significantly stimulate the specific CTL activity of murine spleen, which suggests that the fusion cells have already obtained the function of antigen presenting of parental DC and could present H(22)specific antigen which has not been identified yet, and H(22)-DC could induce antitumor immune response; although simply mixed H(22) cells with DC could stimulate the specific CTL activity which could inhibit the growth of tumor in some degree, it could not prevent the generation of tumor. It shows that the DC vaccine is likely to become a helpful approach in immunotherapy of hepatocarcinoma.
基金supported by grants from the Ministry of Science and Technology of Taiwan(Grant number:MOST 106-2320-B-037008-MY2,MOST 108-2320-B-037-022-MY3,108-2811-B-037-511,and 109-2927-I-037-502)funded by the Drug Development and Value Creation Research Center,Kaohsiung Medical UniversityDepartment of Medical Research,Kaohsiung Medical University Hospital(Grant number:KMU-TC108A03-11)。
文摘This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm,and the protoplasts of C.militaris were inactivated by UV radiation to invalidate their genome function,then they were fused under optimal conditions to get a fusion rate as(7.42±0.8)×10^(-6) fusants/mL;the new fusants were abbreviated as Ac-Cm.On the other hand,when A.cinnamomea and C.militaris were treated with heat and UV oppositely using similar experiments,the fusion rate was(9.70±0.68)×10^(-5) fusants/mL,and the new fusants were abbreviated as Cm-Ac.We selected each of two best-growing fused colonies Ac-Cm-1,Ac-Cm-2,Cm-Ac-1,and Cm-Ac-2,together with parental A.cinnamomea and C.militaris,and studied their morphology,growth antagonism tests,and genetic relationships by 18 S rRNA sequencing.In comparison with the initial cultures of 4 fusants,the yields of adenosine,biomass,cordycepic acid,cordycepin,total polysaccharide,and total triterpenoids were increased up 1.305-50.1563 times in the optimal medium conditions.For gene stability tests,those of the four fusants and their outputs were stabilized within 10 generations.
文摘Secretory carcinoma（SC）, previously described as mammary analogue secretory carcinoma（MASC）, is a recently described salivary gland tumor which morphologically resembles mammary secretory carcinoma. The first description of SC/MASC, reported by Skálová et al. in 2010, was as a rare salivary carcinoma imitating secretory carcinoma of the breast. SC/MASC is a unique salivary gland tumor with morphological overlap with acinic cell carcinoma（Aci CC）, mucoepidermoid carcinoma（MEC）, and adenocarcinoma not otherwise specified（ADCNOS）. SC/MASC shares similar clinicopathological features with Aci CC. As a critical difference between SC/MASC and Aci CC, SC/MASC characteristically has the chromosomal translocation t（12;15）（p13;q25） which leads to a fusion gene between the ETV6 gene on chromosome 12 and the NTRK3 gene on chromosome 15. This genetic background is an important differential diagnostic finding for excluding other salivary gland tumors and may be a critical factor determining the prognosis for patients with SC/MASC. Research in recent years has provided a large body of new data on SC/MASC and suggests the possibility that the ETV6-NTRK3 translocation could be a therapeutic target. Here, we review the morphological and clinicopathological features of SC/MASC and discuss new directions for therapy.
文摘Objective： To investigate the immunotherapy efficacy of fusion cells （dendritic-C6anti-TGF-β1 cells） in the treatment of intraeranial gliomas. Methods： Dendritic cells were isolated from rat bone-marrow precursors stimulated in vitro with granuloeyte-macrophage colony-stimulating factor （GM-CSF） and Interleukin-4 （IL-4）. C6anti-TGF-β1 cells originally from C6 cell line of a rat glioblastoma were transfected with plasmid of TGF-β1 anti-sense gene. Fusions of dendritic cells and C6anti-TGF-β1 cells were prepared by polyethylene glycol （PEG）. The DC/C6anti-TGF-β1 fusion cells were observed and confirmed by fight microscopy and scanning electron microscopy. Experimental rats were divided into three groups at random： C6 cells （Ⅰ）, dendritic-C6anti-TGF-β1 fusion cells and C6 cells （Ⅱ） and IMDM medium only （Ⅲ）. The cells were injected into right parietal lobe region of the rat with stereotaxic technique. Histology, tumor necrosis and survival time were evaluated. Results： Compared with the rats that received C6 cells （survival median time was less than 20 days, tumor region was seen in all fields of observed）, the rats injected with dendritic-C6anti-TGF-β1 fusion cells and C6 cells got a more prolonged life span （more than 59 days）, as well as less tumor region （5.01%-6.2%）. There was no tumor necrosis, but some glias were seen in surroundings. All rats were survived and no necrosis was observed in negative control group. Statistical analysis showed that group Ⅱ had significant difference compared with group Ⅰ. Conclusions： Dendritic-C6anti-TGF-β1 fusion cells could prolong the life span of rats, providing a strategy to achieve an antitumor response against tumors in the central nervous system.
基金supported by the National Natural Science Foundation(81900070)the Natural Science Foundation of Hunan Province(2020JJ5813)China。
文摘The genomic fusions of the anaplastic lymphoma kinase(ALK)gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma(NSCLC).The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions.Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan.Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung.Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases.Immunohistochemical(IHC)staining demonstrated positivity for thyroid transcription factor 1(TTF-1)and ALK-D5F3 in tumor cells,while negativity for P40.The next-generation sequencing(NGS)tests identified a PNPT1-ALK(Exon22:Exon20)fusion variant in case 1 and a TCEAL2-ALK(Exon3:Exon19)fusion variant in case 2.The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system(ARMS)-PCR at the mRNA level.Both patients were treated with oral alectinib at a dosage of 600 mg twice daily.The tumors in both patients were significantly decreased after alectinib treatment,achieving partial response.At the time of submission,there was an absence of disease progression and the progression-free survival(PFS)had surpassed 1 year.It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK(Exon22:Exon20)fusion or a TCEAL2-ALK(Exon3:Exon19)fusion,experience favorable therapeutic outcomes through the administration of alectinib.This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors(TKIs).
文摘In the standard fusion reactors, mainly tokamaks, the mechanical gain obtained is below 1. On the other hand, there are colliding beam fusion reactors, for which, the not neutral plasma and the space charge limit the number of fusions to a very small number. Consequently, the mechanical gain is extremely low. The proposed reactor is also a colliding beam fusion reactor, configured in Stellarator, using directed beams. D+/T+ ions are injected in opposition, with electrons, at high speeds, so as to form a neutral beam. All these particles turn in a magnetic loop in form of figure of “0” (“racetrack”). The plasma is initially non-thermal but, as expected, rapidly becomes thermal, so all states between non-thermal and thermal exist in this reactor. The main advantage of this reactor is that this plasma after having been brought up near to the optimum conditions for fusion (around 68 keV), is then maintained in this state, thanks to low energy non-thermal ions (≤15 keV). So the energetic cost is low and the mechanical gain (</span><i><span style="font-family:Verdana;">Q</span></i><span style="font-family:Verdana;">) is high (</span></span><span style="font-family:Verdana;">>></span><span style="font-family:Verdana;">1). The goal of this article is to study a different type of fusion reactor, its advantages (no net plasma current inside this reactor, so no disruptive instabilities and consequently a continuous working, a relatively simple way to control the reactor thanks to the particles injectors), and its drawbacks, using a simulator tool. The finding results are valuable for possible future fusion reactors able to generate massive energy in a cleaner and safer way than fission reactors.
文摘Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.
基金supported by AGAUR-FI Joan Orófellowship(2024 FI-100399)from the Generalitat de Catalunyasupported by grants from the Fundación AstraZeneca“Jóvenes Investigadores”program+2 种基金upported by grants from the Spanish Ministry of Science,Innovation and University(PID2023-146827OB-I00)“Ramon y Cajal”program(RYC2020-029098-I)FERO Foundation,Fundación AstraZeneca“Jóvenes Investigadores”program,and Cancer Core Europe TRYTRAC program。
文摘In a recent issue of The New England Journal of Medicine,an international team reported the final results of the Phase 2 eNRGy trial(NCT02912949),which evaluated the efficacy and safety of zenocutuzumab,a bispecific antibody against epidermal growth factor receptors 2 and 3(HER2 and HER3),in patients with Neuregulin 1(NRG1)fusion-positive solid tumors.1 The trial yielded compelling evidence of zenocutuzumab’s robust clinical efficacy in this molecularly defined population,accompanied by a favorable tolerability profile.
基金Supported by the Scientific Research Projects of the Health System in Pingshan District,No.2023122.
文摘BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.
文摘BACKGROUND Salvage of the infected long stem revision total knee arthroplasty is challenging due to the presence of well-fixed ingrown or cemented stems.Reconstructive options are limited.Above knee amputation(AKA)is often recommended.We present a surgical technique that was successfully used on four such patients to convert them to a knee fusion(KF)using a cephalomedullary nail.CASE SUMMARY Four patients with infected long stem revision knee replacements that refused AKA had a single stage removal of their infected revision total knee followed by a KF.They were all treated with a statically locked antegrade cephalomedullary fusion nail,augmented with antibiotic impregnated bone cement.All patients had successful limb salvage and were ambulatory with assistive devices at the time of last follow-up.All were infection free at an average follow-up of 25.5 months(range 16-31).CONCLUSION Single stage cephalomedullary nailing can result in a successful KF in patients with infected long stem revision total knees.
基金Supported by Xuhui District Health Commission,No.SHXH202214.
文摘Gastrointestinal tumors require personalized treatment strategies due to their heterogeneity and complexity.Multimodal artificial intelligence(AI)addresses this challenge by integrating diverse data sources-including computed tomography(CT),magnetic resonance imaging(MRI),endoscopic imaging,and genomic profiles-to enable intelligent decision-making for individualized therapy.This approach leverages AI algorithms to fuse imaging,endoscopic,and omics data,facilitating comprehensive characterization of tumor biology,prediction of treatment response,and optimization of therapeutic strategies.By combining CT and MRI for structural assessment,endoscopic data for real-time visual inspection,and genomic information for molecular profiling,multimodal AI enhances the accuracy of patient stratification and treatment personalization.The clinical implementation of this technology demonstrates potential for improving patient outcomes,advancing precision oncology,and supporting individualized care in gastrointestinal cancers.Ultimately,multimodal AI serves as a transformative tool in oncology,bridging data integration with clinical application to effectively tailor therapies.
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
