Metastatic renal cell carcinoma(mRCC)presents with bone metastases in around 20%-30%of patients enrolled in the most recent first-line clinical trials.Emergence of several new agents in first line,in both monotherapy ...Metastatic renal cell carcinoma(mRCC)presents with bone metastases in around 20%-30%of patients enrolled in the most recent first-line clinical trials.Emergence of several new agents in first line,in both monotherapy and combination,has significantly improved patient outcomes.However,the activity of such agents on bone metastases is unclear and management of these patients is complex,due to potential complications that can significantly impair quality of life.This review addresses mRCC diagnosis and monitoring and summarizes the current evidence on systemic therapy,ablative therapies such as stereotactic ablative radiotherapy and surgery,and supportive therapy with bone-targeting agents for these patients,with the goal of improving their outcomes.展开更多
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
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
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
Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsa...Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.展开更多
The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with...The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with metastatic colorectal cancer (mCRC). In this review we summarize the most relevant clinical data on VEGF and EGFR targeting regimens in mCRC. The effects of available treatment strategies for mCRC are often temporary, with resistance and disease progression developing in most patients. Thus, new treatment strategies are urgently needed. Some GI peptides including gastrin and gastrin releasing peptide, certain growth factors such as insulin-like growth factor-I and II and neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in the growth of CRC. Experimental investigations in CRC with antagonistic analogs of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can be targeted to peptide receptors on tumors, are summarized in the second part of the review.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
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
To the Editor:Liver resection,particularly anatomical hepatectomy,has become a vital surgical approach for managing a range of liver diseases[1].Owing to its deep anatomical position,the caudate lobe is frequently imp...To the Editor:Liver resection,particularly anatomical hepatectomy,has become a vital surgical approach for managing a range of liver diseases[1].Owing to its deep anatomical position,the caudate lobe is frequently implicated in hepatobiliary diseases,necessitating precise evaluation and targeted treatment during anatomical liver resection[2,3].The caudate lobe's vascular anatomy is complex:the left portal vein branch(G1L,LPb)primarily supplies the Spiegel lobe,the bifurcation branch(G1F,HBb)feeds the paracaval region or caudate process,and the right posterior portal branch(G1C,RPb)serves the caudate process[4,5].展开更多
Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this...Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this study,we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/-mice with spontaneously diabetic Ins2^(Akita)(Akita)mice.Blood glucose levels and body weights were monitored from 2-32 weeks of age.When mice were 32 weeks of age,behavioral tests were performed,including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory.IL-17A levels in the serum,cerebrospinal fluid,and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction.Moreover,proteins related to cognitive dysfunction(amyloid precursor protein,β-amyloid cleavage enzyme 1,p-tau,and tau),apoptosis(caspase-3 and-9),inflammation(inducible nitric oxide synthase and cyclooxygenase 2),and occludin were detected by western blot assays.Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interferon-γin serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays.Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining.Compared with that in wild-type mice,mice with diabetic encephalopathy had higher IL-17A levels in the serum,cerebrospinal fluid,and hippocampus;downregulation of occludin expression;lower cognitive ability;greater loss of hippocampal neurons;increased microglial activation;and higher expression of inflammatory factors in the serum and hippocampus.IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy.These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy.Furthermore,IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects.These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.展开更多
Objective: to explain and reveal the treatment methods and actual effect of headache patients in neurology department. Methods: from January 2020 to January 2022, 256 patients with headache in neurology department wer...Objective: to explain and reveal the treatment methods and actual effect of headache patients in neurology department. Methods: from January 2020 to January 2022, 256 patients with headache in neurology department were randomly divided into two groups, 128 patients in each group. The reference group received routine treatment and the research group received targeted treatment. The effective rate measurement items of the two groups were measured and compared, as well as SAS measurement items, SDS measurement items, SF-36 measurement items and PSQI measurement items before and after treatment. Results: the measurement items of treatment efficiency in the research group were higher than those in the reference group (p < 0.05). Before treatment, SAS measurement items and SDS measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the SAS measurement items and SDS measurement items of the study group were lower than those of the reference group (P < 0.05). Before treatment, the SF-36 measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the SF-36 measurement items in the study group were higher than those in the reference group (P < 0.05). Before treatment, the PSQI measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the PSQI measurement items of the research group were lower than those of the reference group (P < 0.05). Conclusion: targeted therapy for headache patients in neurology department is effective and worthy of promotion.展开更多
A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disea...A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.展开更多
Polycrystalline Cr2AlC coatings were prepared on M38G superalloy using a two-step method consisting of magnetron sputtering from Cr-Al-C composite targets at room temperature and subsequent annealing at 620 ℃. Partic...Polycrystalline Cr2AlC coatings were prepared on M38G superalloy using a two-step method consisting of magnetron sputtering from Cr-Al-C composite targets at room temperature and subsequent annealing at 620 ℃. Particularly, various targets synthesized by hot pressing mixture of Cr, Al, and C powders at 650-1000 ℃ were used. It was found that regardless of the phase compositions and density of the com- posite targets, when the molar ratio of Cr：Al：C in the starting materials was 2：1：1, phase-pure crystalline Cr2AlC coatings were prepared by magnetron sputtering and post crystallization. The Cr2AIC coatings were dense and crack-free and had a duplex structure. The adhesion strength of the coating deposited on M38G superalloy from the 800 ℃ hot-pressed target and then annealed at 620 ℃ for 20 h in Ar exceeded 82 ± 6 MPa, while its hardness was 12 ± 3 GPa.展开更多
Hypertension is a public health problem that affects both developed and developing countries. Senegal is making significant progress in the fight against this and other chronic, non-communicable diseases. Achieving bl...Hypertension is a public health problem that affects both developed and developing countries. Senegal is making significant progress in the fight against this and other chronic, non-communicable diseases. Achieving blood pressure control within three months of treatment is an important pillar of Senegal’s strategy. The objective of this study was to evaluate the achievement of blood pressure control within three months of treatment at SCL. Our results show the need to strengthen blood pressure management skills of healthcare staff.展开更多
Untethered and self-transformable miniature robots are capable of performing reconfigurable deformation and on-demand locomotion,which aid the traversal toward various lumens,and bring revolutionary changes for target...Untethered and self-transformable miniature robots are capable of performing reconfigurable deformation and on-demand locomotion,which aid the traversal toward various lumens,and bring revolutionary changes for targeted delivery in gastrointestinal(GI)tract.However,the viscous non-Newtonian liquid environment and plicae gastricae obstacles severely hamper high-precision actuation and payload delivery.Here,we developed a low-friction soft robot by assembly of densely arranged cone structures and grafting of hydrophobic monolayers.The magnetic orientation encoded robot can move in multiple modes,with a substantially reduced drag,terrain adaptability,and improved motion velocity across the non-Newtonian liquids.Notably,the robot stiffness can be reversibly controlled with magnetically induced hardening,enabling on-site scratching and destruction of antibiotic-ineradicable polymeric matrix in biofilms with a low-frequency magnetic field.Furthermore,the magnetocaloric effect can be utilized to eradicate the bacteria by magnetocaloric effect under high-frequency alternating field.To verify the potential applications inside the body,the clinical imaging-guided actuation platforms were developed for vision-based control and delivery of the robots.The developed low-friction robots and clinical imaging-guided actuation platforms show their high potential to perform bacterial infection therapy in various lumens inside the body.展开更多
Despite hepatocellular carcinoma’s position as the second most common pediatric liver tumor,it is a rare tumor in children warranting international collaboration to improve outcomes.Few cases diagnosed in earlier sta...Despite hepatocellular carcinoma’s position as the second most common pediatric liver tumor,it is a rare tumor in children warranting international collaboration to improve outcomes.Few cases diagnosed in earlier stages,when confined to the liver and responding to systemic treatment or with resectable metastases,may be cured by complete resection and/or orthotopic transplantation.Complete resection is the only chance for cure;therefore,all attempts should be made to make these options available.Despite modest progress in locoregional treatments,these serve in most cases as palliative treatment or as a bridge to definitive treatment at best.Currently used systemic treatments have response rates below 50%.Five-year survival in advanced stages is below 30%.The international Paediatric Hepatic International Tumour Trial trial is evaluating novel systemic treatments in pediatric hepatocellular carcinoma.Patients suffering from these tumors likely benefit from targeted treatment based on molecular aberrations corresponding with tumor subtype.展开更多
Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macu...Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.展开更多
Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting...Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were ＂angiogenesis＂, ＂ascular targeting treatment＂ and ＂endothelial progenitor cells＂. Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells. Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature＇s resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor. Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included. This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment. Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.展开更多
The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and ...The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.展开更多
文摘Metastatic renal cell carcinoma(mRCC)presents with bone metastases in around 20%-30%of patients enrolled in the most recent first-line clinical trials.Emergence of several new agents in first line,in both monotherapy and combination,has significantly improved patient outcomes.However,the activity of such agents on bone metastases is unclear and management of these patients is complex,due to potential complications that can significantly impair quality of life.This review addresses mRCC diagnosis and monitoring and summarizes the current evidence on systemic therapy,ablative therapies such as stereotactic ablative radiotherapy and surgery,and supportive therapy with bone-targeting agents for these patients,with the goal of improving their outcomes.
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%.
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the National Natural Science Foundation of China,No.82073338Sichuan Science and Technology Support Project,No.2021YFSY0039 and No.22ZDYF0499+1 种基金1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,No.2020HXFH0021.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC21059.
文摘Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.
文摘The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with metastatic colorectal cancer (mCRC). In this review we summarize the most relevant clinical data on VEGF and EGFR targeting regimens in mCRC. The effects of available treatment strategies for mCRC are often temporary, with resistance and disease progression developing in most patients. Thus, new treatment strategies are urgently needed. Some GI peptides including gastrin and gastrin releasing peptide, certain growth factors such as insulin-like growth factor-I and II and neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in the growth of CRC. Experimental investigations in CRC with antagonistic analogs of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can be targeted to peptide receptors on tumors, are summarized in the second part of the review.
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.
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
基金supported by the grants from the Natural Science Foundation of China(82173129 and 82203330)China Post-doctoral Science Foundation(2022M711589)+1 种基金Distinguished Youth Project of Nanjing Drum Tower HospitalNanjing Health Science and Technology Development Project(YKK22065)。
文摘To the Editor:Liver resection,particularly anatomical hepatectomy,has become a vital surgical approach for managing a range of liver diseases[1].Owing to its deep anatomical position,the caudate lobe is frequently implicated in hepatobiliary diseases,necessitating precise evaluation and targeted treatment during anatomical liver resection[2,3].The caudate lobe's vascular anatomy is complex:the left portal vein branch(G1L,LPb)primarily supplies the Spiegel lobe,the bifurcation branch(G1F,HBb)feeds the paracaval region or caudate process,and the right posterior portal branch(G1C,RPb)serves the caudate process[4,5].
基金supported by the Natural Science Foundation of Jiangsu Province of China, No.BK20180948(to ZL)Nantong Applied Research Program of China, No.MS12019011(to XXF)Science and Technology Project of Nantong University of China, No.TDYXY2019007(to XXF)
文摘Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this study,we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/-mice with spontaneously diabetic Ins2^(Akita)(Akita)mice.Blood glucose levels and body weights were monitored from 2-32 weeks of age.When mice were 32 weeks of age,behavioral tests were performed,including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory.IL-17A levels in the serum,cerebrospinal fluid,and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction.Moreover,proteins related to cognitive dysfunction(amyloid precursor protein,β-amyloid cleavage enzyme 1,p-tau,and tau),apoptosis(caspase-3 and-9),inflammation(inducible nitric oxide synthase and cyclooxygenase 2),and occludin were detected by western blot assays.Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interferon-γin serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays.Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining.Compared with that in wild-type mice,mice with diabetic encephalopathy had higher IL-17A levels in the serum,cerebrospinal fluid,and hippocampus;downregulation of occludin expression;lower cognitive ability;greater loss of hippocampal neurons;increased microglial activation;and higher expression of inflammatory factors in the serum and hippocampus.IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy.These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy.Furthermore,IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflammation and cognitive defects.These results highlight a role for IL-17A as a mediator of diabetic encephalopathy and potential target for the treatment of cognitive impairment induced by diabetic encephalopathy.
文摘Objective: to explain and reveal the treatment methods and actual effect of headache patients in neurology department. Methods: from January 2020 to January 2022, 256 patients with headache in neurology department were randomly divided into two groups, 128 patients in each group. The reference group received routine treatment and the research group received targeted treatment. The effective rate measurement items of the two groups were measured and compared, as well as SAS measurement items, SDS measurement items, SF-36 measurement items and PSQI measurement items before and after treatment. Results: the measurement items of treatment efficiency in the research group were higher than those in the reference group (p < 0.05). Before treatment, SAS measurement items and SDS measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the SAS measurement items and SDS measurement items of the study group were lower than those of the reference group (P < 0.05). Before treatment, the SF-36 measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the SF-36 measurement items in the study group were higher than those in the reference group (P < 0.05). Before treatment, the PSQI measurement items of the study group were approximately equal to those of the reference group (P > 0.05). After treatment, the PSQI measurement items of the research group were lower than those of the reference group (P < 0.05). Conclusion: targeted therapy for headache patients in neurology department is effective and worthy of promotion.
文摘A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.
基金supported by the National Natural Science Foundation of China under Grant Nos.51271191,51571205 and 51401209
文摘Polycrystalline Cr2AlC coatings were prepared on M38G superalloy using a two-step method consisting of magnetron sputtering from Cr-Al-C composite targets at room temperature and subsequent annealing at 620 ℃. Particularly, various targets synthesized by hot pressing mixture of Cr, Al, and C powders at 650-1000 ℃ were used. It was found that regardless of the phase compositions and density of the com- posite targets, when the molar ratio of Cr：Al：C in the starting materials was 2：1：1, phase-pure crystalline Cr2AlC coatings were prepared by magnetron sputtering and post crystallization. The Cr2AIC coatings were dense and crack-free and had a duplex structure. The adhesion strength of the coating deposited on M38G superalloy from the 800 ℃ hot-pressed target and then annealed at 620 ℃ for 20 h in Ar exceeded 82 ± 6 MPa, while its hardness was 12 ± 3 GPa.
文摘Hypertension is a public health problem that affects both developed and developing countries. Senegal is making significant progress in the fight against this and other chronic, non-communicable diseases. Achieving blood pressure control within three months of treatment is an important pillar of Senegal’s strategy. The objective of this study was to evaluate the achievement of blood pressure control within three months of treatment at SCL. Our results show the need to strengthen blood pressure management skills of healthcare staff.
基金supported by the National Natural Science Foundation of China(22102104 and U22A2064)the General Research Fund(project no.14203123)+7 种基金National Key Research and Development Project(grant no.2023YFB4705300)the Shenzhen Science and Technology Program(JCYJ20220531103409021 and JCYJ20220818101611025)the Guangdong Basic and Applied Basic Research Foundation(2021A1515010672 and 2022B1515120010)the Research Impact Fund(project no.R4015-21)Research Fellow Scheme(project no.RFS2122-4S03)the EU-Hong Kong Research and Innovation Cooperation Co-funding Mechanism(project no.E-CUHK401/20)from the Research Grants Council(RGC)of Hong Kongthe support from the SIATCUHK Joint Laboratory of Robotics and Intelligent Systems and the Multi-Scale Medical Robotics Center(MRC),InnoHK,at the Hong Kong Science ParkGuangdong University Students Science and Technology Innovation Cultivation Special Fund Project with project no.pdjh2022b0446.
文摘Untethered and self-transformable miniature robots are capable of performing reconfigurable deformation and on-demand locomotion,which aid the traversal toward various lumens,and bring revolutionary changes for targeted delivery in gastrointestinal(GI)tract.However,the viscous non-Newtonian liquid environment and plicae gastricae obstacles severely hamper high-precision actuation and payload delivery.Here,we developed a low-friction soft robot by assembly of densely arranged cone structures and grafting of hydrophobic monolayers.The magnetic orientation encoded robot can move in multiple modes,with a substantially reduced drag,terrain adaptability,and improved motion velocity across the non-Newtonian liquids.Notably,the robot stiffness can be reversibly controlled with magnetically induced hardening,enabling on-site scratching and destruction of antibiotic-ineradicable polymeric matrix in biofilms with a low-frequency magnetic field.Furthermore,the magnetocaloric effect can be utilized to eradicate the bacteria by magnetocaloric effect under high-frequency alternating field.To verify the potential applications inside the body,the clinical imaging-guided actuation platforms were developed for vision-based control and delivery of the robots.The developed low-friction robots and clinical imaging-guided actuation platforms show their high potential to perform bacterial infection therapy in various lumens inside the body.
文摘Despite hepatocellular carcinoma’s position as the second most common pediatric liver tumor,it is a rare tumor in children warranting international collaboration to improve outcomes.Few cases diagnosed in earlier stages,when confined to the liver and responding to systemic treatment or with resectable metastases,may be cured by complete resection and/or orthotopic transplantation.Complete resection is the only chance for cure;therefore,all attempts should be made to make these options available.Despite modest progress in locoregional treatments,these serve in most cases as palliative treatment or as a bridge to definitive treatment at best.Currently used systemic treatments have response rates below 50%.Five-year survival in advanced stages is below 30%.The international Paediatric Hepatic International Tumour Trial trial is evaluating novel systemic treatments in pediatric hepatocellular carcinoma.Patients suffering from these tumors likely benefit from targeted treatment based on molecular aberrations corresponding with tumor subtype.
基金This research was supported by the National Natural Science Foundation of China(No.81670895 and 81970839 to L.H.,81700841 to J.L.)the Department of Science and Technology of Sichuan Province,China(No.21ZDYF0551 to L.H2016FZ0091 to Ling Wan).
文摘Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%–71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.
文摘Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were ＂angiogenesis＂, ＂ascular targeting treatment＂ and ＂endothelial progenitor cells＂. Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells. Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature＇s resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor. Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included. This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment. Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.
基金partially supported by grants from the Non-communicable Chronic Diseases-National Science and Technology Major Project(grant num-ber:2023ZD0510300)the National Natural Science Foundation of China(grant numbers:82403377,82473192).
文摘The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.
