N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,mat...N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,maturation,nucleocytoplasmic transport,translation efficiency,phase separation,and sta-bility,thereby linking its dysregulation to diverse physiological and pathological processes.METTL3,a core catalytic component of the methyltransferase complex responsible for m6A deposition,is frequently dysregulated in diseases,including colorectal cancer(CRC).Although METTL3’s involvement in CRC pathogenesis has been documented,its precise molecular mechanisms and functional roles remain incompletely understood.METTL3 mediates CRC progression-encompa-ssing proliferation,invasion,drug resistance,and metabolic reprogramming-through m6A-dependent modulation of both coding RNAs and noncoding RNAs.Its regulatory effects are primarily attributed to interactions with key signaling pathways at multiple stages of CRC development.Emerging evidence highlights METTL3 as a promising biomarker for CRC diagnosis and prognosis,as well as a potential therapeutic target.By synthesizing recent advances in METTL3 research within CRC,this review provides critical insights into novel strategies for clinical diagnosis and targeted therapy.展开更多
β-Amyloid （Aβ） over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer＇s disease （AD）.Studies on them may help elucidate the precise molecular patho...β-Amyloid （Aβ） over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer＇s disease （AD）.Studies on them may help elucidate the precise molecular pathogenesis of AD.Until now,although tau protein and Aβ remain the foci of AD research,the etiopathogenesis of AD and effective drugs for AD treatment are still largely unsolved.The present review was mainly focused on the molecular mechanism of Aβ aggregation-related impairment and the pathways leading to tau hyperphosphorylation,based on which some promising therapeutic targets for AD were also proposed.展开更多
Laser powder bed fusion(L-PBF)was utilized to produce specimens in Ti-6Al-4V,which were subjected to a bi-lamellar heat treatment,which produces microstructures consisting of primary α-lamellae and a fine secondary ...Laser powder bed fusion(L-PBF)was utilized to produce specimens in Ti-6Al-4V,which were subjected to a bi-lamellar heat treatment,which produces microstructures consisting of primary α-lamellae and a fine secondary α-phase inside the inter-lamellar β-regions.The bi-lamellar microstructure was obtained as(i)a direct bi-lamellar heat treatment from the asbuilt condition or(ii)a bi-lamellar heat treatment preceded by a β-homogenization.For the bi-lamellar treatment with β-homogenization,cooling rates in the range 1-500 K/min were applied after homogenization in β-region followed by inter-critical annealing in the α+β region at various temperatures in the range 850-950℃.The microstructures were characterized using various microscopical techniques.Mechanical testing with Vickers hardness indentation and tensile testing was performed.The bi-lamellar microstructure was harder when compared to a soft fully lamellar microstructure,because of the presence of fine α-platelets inside the β-lamellae.Final low temperature ageing provided an additional hardness increase by precipitation hardening of the primary α-regions.The age hardened bi-lamellar microstructure shows a similar hardness as the very fine,as-built martensitic microstructure.The bi-lamellar microstructure has more favorable mechanical properties than the as-built condition,which has high strength,but poor ductility.After the bi-lamellar heat treatment,the elongation was improved by more than 250%.Due to the very high strength of the as-built condition,loss of tensile strength is unavoidable,resulting in a reduction of tensile strength of~18%.展开更多
Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatica...Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.展开更多
Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenes...Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.展开更多
The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (...The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.展开更多
We present an interesting case of a 56-year-old female diagnosed with invasive high-grade triple-negative breast cancer, who developed diffuse liver metastases following lumpectomy and combination chemotherapy with do...We present an interesting case of a 56-year-old female diagnosed with invasive high-grade triple-negative breast cancer, who developed diffuse liver metastases following lumpectomy and combination chemotherapy with docetaxel, doxorubicin and cyclophosphamide, re-excision and radiation therapy. Restaging CT and PET scans revealed massive involvement of the liver. She was treated with a combination of gene targeted and cytotoxic chemotherapy including capecitabine, erlotinib, bevacizumab and phenylbutyrate. She tested weakly positive for HER-2 despite prior negative FISH, which prompted us to add trastuzumab to her regimen. Baseline CT revealed five liver tumors—the sum of the products of the two largest perpendicular diameters was 110 cm2. Follow-up CT after three months of treatment revealed 62% decrease in total tumor load. More than 50% decrease in tumor size persisted on two follow-up CT scans, confirming partial response. She developed progressive disease after 15 months of treatment. A group of 16 women, including this patient, diagnosed with triple negative breast cancer with distant metastases were treated by our team with a combination of gene targeted therapy and chemotherapy. Six percent of patients obtained partial response, 25% minor response, 31% stable disease, and 38% progressive disease. The median duration of treatment in patients who relapsed after the second-, third- and fourth- to seventh-lines of chemotherapy was 59 weeks, 22 weeks and 17 weeks, respectively. Comparison of results obtained with cytotoxic chemotherapy revealed that MDT in the second- and third-lines was only nine and four weeks, respectively. In conclusion, this case report indicates that it is possible to obtain durable objective response of recurrent TNBC with a combination of gene targeted agents.展开更多
<strong>Introduction:</strong> Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a...<strong>Introduction:</strong> Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. <strong>Materials and Methods:</strong> CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span> - 182<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, the collimator angles of each arc were set to 90<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, Octavius<span style="white-space:nowrap;"><sup>®</sup></span> 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. <strong>Results:</strong> A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. <strong>Conclusion:</strong> Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.展开更多
Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after...Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after nerve injury,which was clearly observed by Ramon y Cajal in the early 20^(th) century(1,2).Due to lack展开更多
基金Supported by Jiangxi Provincial Natural Science Foundation,No.20242BAB25454the Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular of Ministry of Education of Gannan Medical University,No.XN202013+1 种基金Science and Technology Research Project of Jiangxi Provincial Department of Education,No.GJJ201528Startup Foundation for Advanced Talents of Gannan Medical University,No.QD202124.
文摘N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,maturation,nucleocytoplasmic transport,translation efficiency,phase separation,and sta-bility,thereby linking its dysregulation to diverse physiological and pathological processes.METTL3,a core catalytic component of the methyltransferase complex responsible for m6A deposition,is frequently dysregulated in diseases,including colorectal cancer(CRC).Although METTL3’s involvement in CRC pathogenesis has been documented,its precise molecular mechanisms and functional roles remain incompletely understood.METTL3 mediates CRC progression-encompa-ssing proliferation,invasion,drug resistance,and metabolic reprogramming-through m6A-dependent modulation of both coding RNAs and noncoding RNAs.Its regulatory effects are primarily attributed to interactions with key signaling pathways at multiple stages of CRC development.Emerging evidence highlights METTL3 as a promising biomarker for CRC diagnosis and prognosis,as well as a potential therapeutic target.By synthesizing recent advances in METTL3 research within CRC,this review provides critical insights into novel strategies for clinical diagnosis and targeted therapy.
基金supported by National Natural Science Foundation of China(No.30672450)
文摘β-Amyloid （Aβ） over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer＇s disease （AD）.Studies on them may help elucidate the precise molecular pathogenesis of AD.Until now,although tau protein and Aβ remain the foci of AD research,the etiopathogenesis of AD and effective drugs for AD treatment are still largely unsolved.The present review was mainly focused on the molecular mechanism of Aβ aggregation-related impairment and the pathways leading to tau hyperphosphorylation,based on which some promising therapeutic targets for AD were also proposed.
基金This research was conducted in connection with the AM-LINE4.0 project(No.7076-00074B)funded by the Danish Innovation Fund。
文摘Laser powder bed fusion(L-PBF)was utilized to produce specimens in Ti-6Al-4V,which were subjected to a bi-lamellar heat treatment,which produces microstructures consisting of primary α-lamellae and a fine secondary α-phase inside the inter-lamellar β-regions.The bi-lamellar microstructure was obtained as(i)a direct bi-lamellar heat treatment from the asbuilt condition or(ii)a bi-lamellar heat treatment preceded by a β-homogenization.For the bi-lamellar treatment with β-homogenization,cooling rates in the range 1-500 K/min were applied after homogenization in β-region followed by inter-critical annealing in the α+β region at various temperatures in the range 850-950℃.The microstructures were characterized using various microscopical techniques.Mechanical testing with Vickers hardness indentation and tensile testing was performed.The bi-lamellar microstructure was harder when compared to a soft fully lamellar microstructure,because of the presence of fine α-platelets inside the β-lamellae.Final low temperature ageing provided an additional hardness increase by precipitation hardening of the primary α-regions.The age hardened bi-lamellar microstructure shows a similar hardness as the very fine,as-built martensitic microstructure.The bi-lamellar microstructure has more favorable mechanical properties than the as-built condition,which has high strength,but poor ductility.After the bi-lamellar heat treatment,the elongation was improved by more than 250%.Due to the very high strength of the as-built condition,loss of tensile strength is unavoidable,resulting in a reduction of tensile strength of~18%.
文摘Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.
基金the National Natural Science Foundation of China(Grant No.:82360542)Jiangxi Provincial Natural Science Foundation,China(Grant Nos.:20224BAB214030 and 20224BAB216072)+2 种基金Doctoral Startup Fund of Gannan Medical University,China(Grant Nos.:QD202136 and QD202132)Science and Technology Planning Projects of Fuzhou,China(Grant No.:2021FZR0101)the Natural Science Foundation of Fujian Province,China(Grant No.:2022YZ0104).
文摘Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.
文摘The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.
文摘We present an interesting case of a 56-year-old female diagnosed with invasive high-grade triple-negative breast cancer, who developed diffuse liver metastases following lumpectomy and combination chemotherapy with docetaxel, doxorubicin and cyclophosphamide, re-excision and radiation therapy. Restaging CT and PET scans revealed massive involvement of the liver. She was treated with a combination of gene targeted and cytotoxic chemotherapy including capecitabine, erlotinib, bevacizumab and phenylbutyrate. She tested weakly positive for HER-2 despite prior negative FISH, which prompted us to add trastuzumab to her regimen. Baseline CT revealed five liver tumors—the sum of the products of the two largest perpendicular diameters was 110 cm2. Follow-up CT after three months of treatment revealed 62% decrease in total tumor load. More than 50% decrease in tumor size persisted on two follow-up CT scans, confirming partial response. She developed progressive disease after 15 months of treatment. A group of 16 women, including this patient, diagnosed with triple negative breast cancer with distant metastases were treated by our team with a combination of gene targeted therapy and chemotherapy. Six percent of patients obtained partial response, 25% minor response, 31% stable disease, and 38% progressive disease. The median duration of treatment in patients who relapsed after the second-, third- and fourth- to seventh-lines of chemotherapy was 59 weeks, 22 weeks and 17 weeks, respectively. Comparison of results obtained with cytotoxic chemotherapy revealed that MDT in the second- and third-lines was only nine and four weeks, respectively. In conclusion, this case report indicates that it is possible to obtain durable objective response of recurrent TNBC with a combination of gene targeted agents.
文摘<strong>Introduction:</strong> Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. <strong>Materials and Methods:</strong> CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span> - 182<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, the collimator angles of each arc were set to 90<span style="font-family:Verdana, Helvetica, Arial;white-space:normal;background-color:#FFFFFF;">°</span>, Octavius<span style="white-space:nowrap;"><sup>®</sup></span> 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. <strong>Results:</strong> A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. <strong>Conclusion:</strong> Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.
基金supported by National Natural Science Foundation of China [31600839]Guangdong Innovative and Entrepreneurial Research Team Program [2013S046]+1 种基金Shenzhen Peacock Plansupported by Funds of Leading Talents of Guangdong [2013] and Program of Introducing Talents of Discipline to Universities (B14036)
文摘Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after nerve injury,which was clearly observed by Ramon y Cajal in the early 20^(th) century(1,2).Due to lack
