In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in spec...In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in specific genes,type ofβ-cell impairment,degree of insulin resistance,and clinical characteristics of metabolic profiles.Improved classification methods enable healthcare providers to formulate blood glucose management strategies more precisely.Applying these updated classification systems,will assist clinicians in further optimising treatment plans,including targeted drug therapies,personalized dietary advice,and specific exercise plans.Ultimately,this will facilitate stricter blood glucose control,minimize the risks of hypoglycaemia and hyperglycaemia,and reduce long-term complications associated with diabetes.展开更多
The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research ...The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.展开更多
Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular ...Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.展开更多
Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial deliv...Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.展开更多
Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
This paper studies how to effectively improve the English writing skills of college students.It introduces the importance of English writing skills and the current situation,and finds that college students generally h...This paper studies how to effectively improve the English writing skills of college students.It introduces the importance of English writing skills and the current situation,and finds that college students generally have problems such as insufficient vocabulary and frequent grammatical errors;it analyses the advantages and disadvantages of traditional and modern teaching methods,with the traditional method focusing too much on the form,while the modern method may neglect the consolidation of basic knowledge and personalized needs.Effective strategies for university students are proposed,including classroom teaching,personalised instruction and practical activities.In classroom teaching,writing tasks with practical application scenarios are designed and diversified teaching methods are used.In personalised instruction,students’needs are understood and targeted instruction is provided.In practical activities,diverse writing tasks are designed and effective feedback mechanisms are established.Finally,the contributions of the study and future research directions are summarised.展开更多
Although the development of national conditions and the increase in health risk factors undoubtedly pose a huge challenge to China’s medical health and labour security system,these simultaneously promote the elevatio...Although the development of national conditions and the increase in health risk factors undoubtedly pose a huge challenge to China’s medical health and labour security system,these simultaneously promote the elevation and transformation of national healthcare consciousness.Given that the current disease diagnosis and treatment models hardly satisfy the growing demand for medical and health care in China,based on the theory of healthcare and basic laws of human physiological activities,and combined with the characteristics of the information society,this paper presents a panoramic and personalised intelligent healthcare mode that is aimed at improving and promoting individual health.The basic definition and conceptual model are provided,and its basic characteristics and specific connotations are elaborated in detail.Subsequently,an intelligent coordination model of daily time allocation and a dynamic optimisation model for healthcare programmes are proposed.The implementation of this mode is explicitly illustrated with a practical application case.It is expected that this study will provide new ideas for further healthcare research and development.展开更多
Radiology（imaging） and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are traine...Radiology（imaging） and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations（phenotypes） to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype（to obtain genomic information） of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography（CT）, magnetic resonance imaging（MRI）, and positron-emission tomography（PET）, the challenges we are facing, and the potential contribution of radiomics towards precision medicine.展开更多
Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting t...Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked- with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator(RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine(or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among the general population. All of the above techniques for addressing bone defects are discussed in this paper.展开更多
Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control.Despite the prevalence of diabetes in patients admitted to hospital and intensive care units,the ideal manag...Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control.Despite the prevalence of diabetes in patients admitted to hospital and intensive care units,the ideal management of hyperglycaemia in these groups is uncertain.There are data that suggest that acute hyperglycaemia in critically ill patients without diabetes is associated with increased mortality and morbidity.Exogenous insulin to keep blood glucose concentrations < 10 mmol/L is accepted as standard of care in this group.However,preliminary data have recently been reported that suggest that chronic hyperglycaemia may result in conditioning,which protects these patients against damage mediated by acute hyperglycaemia.Furthermore,acute glucose-lowering to < 10 mmol/L in patients with diabetes with inadequate glycaemic control prior to their critical illness appears to have the capacity to cause harm.This review focuses on glycaemic control in critically ill patients with type 2 diabetes,the potential for harm from glucose-lowering and the rationale for personalised therapy.展开更多
Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor(ER)-positive and human epidermal growth factor receptor-2 negative ...Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor(ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.展开更多
In this paper,we describe the design and surgical process of personalised pelvic prostheses fixation through 3D printing according to different Enneking pelvic tumour zones:the ilium(Zone I),acetabulum(Zone II),and pu...In this paper,we describe the design and surgical process of personalised pelvic prostheses fixation through 3D printing according to different Enneking pelvic tumour zones:the ilium(Zone I),acetabulum(Zone II),and pubis and ischium(Zone III).A 3D model of the pelvis was reconstructed using imaging data,and the parameters on the planes of the acetabulum and pelvic incisal margin were measured.The main body of the pelvic prosthesis was constructed,a porous structure was designed on the bone-prosthesis interface,and the movement paths,lengths,and diameters of screws were planned.By combining the pathological model and osteotomy guide,limb salvage reconstruction was performed in patients with pelvic tumours.Preoperative and postoperative data were compared to verify the prosthesis stability.Our investigation revealed that the long-term survival of pelvic reconstruction prostheses depends on accurate matching with the bone defect area,good initial stability,and a porous structure to allow bone ingrowth.展开更多
This study was aimed at comparing the biomechanical performance of personalised 3D-printed clavicle plates of different materials to treat midshaft clavicle fractures with the finite element(FE)method.The FE model of ...This study was aimed at comparing the biomechanical performance of personalised 3D-printed clavicle plates of different materials to treat midshaft clavicle fractures with the finite element(FE)method.The FE model of a fractured clavicle with a personalised 3D-printed clavicle plate and screws was constructed.Three types of materials were simulated,including stainless steel,titanium alloy,and magnesium alloy.Two loading conditions(axial compression and inferior bending)were applied at the distal end of the clavicle to simulate arm abduction.Plate stiffness,peak stress,and bone strain at the clavicle fracture site were measured and compared.The stiffness of the stainless steel clavicle plate was significantly greater than that of the titanium alloy clavicle plate.The stiffness of the magnesium alloy clavicle plate was similar to that of the intact clavicle;peak stress of the magnesium alloy clavicle plate was the lowest;thus,it had less stress-shielding effects on bone formation.The magnesium alloy clavicle plate was more likely to form bone by distributing proper strain at the clavicle fracture site.According to the influence of different materials on the tensile strength,magnesium alloy clavicle plates might be preferred owing to their bionic stiffness in the treatment of patients with a low risk of falling.For patients who engage in contact sports,a titanium alloy clavicle plate might be more suitable.展开更多
In our case,3D printing was used to fabricate a custom-made titanium alloy total talar prosthesis as a mirror image of the contralateral healthy talus for a 16-year-old girl who underwent right talar resection for a r...In our case,3D printing was used to fabricate a custom-made titanium alloy total talar prosthesis as a mirror image of the contralateral healthy talus for a 16-year-old girl who underwent right talar resection for a recurrent giant cell tumour(GCT)of the talus.A porous surface was used over the neck and tail of the talus prosthesis to promote soft tissue attachment and improve the stability of the prosthesis.Pre-drilled medial and lateral holes were prepared for ligament repair and attachment.Eighteen months after the operation,there was no tumour recurrence,and the patient walked without symptoms.The Musculoskeletal Tumour Society score was 22/30,the American Orthopaedic Foot and Ankle Society score was 88/100,and the prosthesis was well positioned on radiographs.The short-and medium-term outcomes indicated that 3D-printed modular talar prostheses could be an effective treatment option.展开更多
Background:Using a pilot randomised controlled trial(RCT),to assess the short-term effectiveness of a structured diabetic retinopathy(DR)-specific,intensive,and personalised care planning(DR-IPCP)intervention on diabe...Background:Using a pilot randomised controlled trial(RCT),to assess the short-term effectiveness of a structured diabetic retinopathy(DR)-specific,intensive,and personalised care planning(DR-IPCP)intervention on diabetes control outcomes in Singaporeans with poorly controlled type 2 diabetes.Methods:Eighteen individuals with mild-moderate DR and poor glycemic control[HbA1c≥64 mmol/mol(≥8.0%)over two consecutive 6-month readings]were randomized to DR-IPCP(n=9)or usual care(UC,n=9).The intervention included a physician consultation,an initial personalised eye consultation with a experienced diabetes nurse educator,and three behaviour change follow-up calls.HbA1c(primary outcome),lipids and blood pressure were assessed at baseline and three months post-intervention.Participant feedback regarding the DR-IPCP program was collected at three months via a semi-structured telephone interview.Results:While no significant between-group differences were observed,DR-IPCP participants experienced significant within-group reductions in HbA1c,total cholesterol,and low density lipoprotein at follow-up compared to baseline[7 mmol/mol(−0.8%),−0.64 mmol/L,and−0.66 mmol/L,respectively].No significant within-group changes in these parameters were observed in the UC group.Following the DR-IPCP intervention,participants reported a clearer understanding of the link between diabetes management;the development and progression of DR.Conclusions:DR-IPCP provides an effective short-term improvement in diabetes control parameters in DR patients with poor diabetes control.An adequately powered and longitudinal RCT is warranted to assess the clinical,patient-centred and economic potential of this programme in this population.展开更多
Existing examinations in postgraduate education and continuing medical education (CME) are not perfect. Modern assessment does not reflect disadvantages of older responders, for whom more time for reply is needed. Spe...Existing examinations in postgraduate education and continuing medical education (CME) are not perfect. Modern assessment does not reflect disadvantages of older responders, for whom more time for reply is needed. Specialists with wide clinical experience may choose more than one correct answer in alternative questions. Reduced ability to remember in older people restricts examination without additional sources of information. We offer an individualised system for testing doctors. It provides personalised choice of examination questions using multiple choice questions with weight characteristics and absence of distractors, interactive cooperation in case of negative answers and the final decision of an expert in relation to the person tested. A special algorithm is proposed for typical questions that combines the advantages of known approaches to testing. The questioning system is complex for the creators of tests, but is more convenient and objective than existing ones for medical doctors.展开更多
Epilepsy is one of the most common neurological disorders,affecting more than 50 million people worldwide.Management is particularly complex in individuals with intellectual disabilities,who are at a much higher risk ...Epilepsy is one of the most common neurological disorders,affecting more than 50 million people worldwide.Management is particularly complex in individuals with intellectual disabilities,who are at a much higher risk of having severe seizures compared to the general population.People with intellectual disabilities are regularly excluded from epilepsy research,despite having significantly higher risks of negative health outcomes and early mortality.Recent advances in artificial intelligence(AI)have shown great potential in improving the diagnosis,monitoring,and management of epilepsy.Machine learning techniques have been used in analysing electroencephalography data for efficient seizure detection and prediction,as well as individualised treatment,which facilitates timely and customised intervention for individuals with epilepsy.Research and implementation of AI-based solutions for people with intellectual disabilities and epilepsy still remains limited due to a lack of accessible long-term clinical data for model training,difficulties in communicating with people with intellectual disabilities,and ethical challenges in ensuring the safety of the AI systems for this population.This paper presents an overview of recent AI applications in epilepsy and for people with intellectual disabilities,highlighting key challenges and the necessity of including people with intellectual disabilities in research on AI and epilepsy,and potential strategies to promote the development and use of AI applications for this vulnerable population.Given the prevalence and consequences associated with epilepsy in people with intellectual disabilities,the application of AI in epilepsy care has the potential to have a significant positive impact.To achieve this impact and to avoid increasing existing health inequity,there is an urgent need for greater inclusion of people with intellectual disabilities in research around the application of AI to epilepsy care and management.展开更多
The gender-affirmative model of care has proven unsuccessful in many cases of gender dysphoria.There is a pressing need to continue research and develop and implement alternative models of care.Personalised models of ...The gender-affirmative model of care has proven unsuccessful in many cases of gender dysphoria.There is a pressing need to continue research and develop and implement alternative models of care.Personalised models of care need to replace the standardised ones to reflect the unique nature of internal issues that exist within every individual.A holistic care model that includes Physical,Mental,Emotional,Social,and Spiritual(PMESS)aspects of a person’s wellbeing indicates an effective way forward.Such a multidimensional model enables a greater understanding of complex relationships between different factors and their effects on health and overall wellbeing.Empowered by intelligent technologies,such as data mining and Artificial Intelligence(AI),the PMESS model can systematically capture,analyse,and evaluate data across the multiple dimensions of the holistic model of care.It can help identify patterns within the data,generate useful insights,and support the development of effective prevention and personalized treatment strategies.The PMESS-AI model supports the collaboration between multiple stakeholders,and the machine learning aspects of it can usher in the discovery of new knowledge and breakthroughs in research.展开更多
Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detri...Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis.In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment.Finally,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.展开更多
The European Society for Organ Transplantation(ESOT)has created a consensus platform for evidence-based and best-practice recommendations.At the 2022 ESOT consensus conference,nine topics were chosen for further explo...The European Society for Organ Transplantation(ESOT)has created a consensus platform for evidence-based and best-practice recommendations.At the 2022 ESOT consensus conference,nine topics were chosen for further exploration based on their potential for impact on healthcare,existing research gaps,and incomplete coverage of the topic in current scientific literature(1).Among these topics,molecular biology testing for non-invasive diagnosis of allograft rejection was a focal point,as detailed in the ESOT consensus statement on biomarkers in liver transplantation(LT)(2).We extend our congratulations to the authors of the liver subgroup on their dedicated effort and rigorous approach in translating major unmet clinical needs into four well-defined questions of interest regarding biomarkers for prediction and/or diagnosis of longer-term complications after LT.展开更多
文摘In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in specific genes,type ofβ-cell impairment,degree of insulin resistance,and clinical characteristics of metabolic profiles.Improved classification methods enable healthcare providers to formulate blood glucose management strategies more precisely.Applying these updated classification systems,will assist clinicians in further optimising treatment plans,including targeted drug therapies,personalized dietary advice,and specific exercise plans.Ultimately,this will facilitate stricter blood glucose control,minimize the risks of hypoglycaemia and hyperglycaemia,and reduce long-term complications associated with diabetes.
基金supported by the Department of Biotechnology(DBT),Government of India(BT/556/NE/U-Excel/).
文摘The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
文摘Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.
文摘Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
文摘This paper studies how to effectively improve the English writing skills of college students.It introduces the importance of English writing skills and the current situation,and finds that college students generally have problems such as insufficient vocabulary and frequent grammatical errors;it analyses the advantages and disadvantages of traditional and modern teaching methods,with the traditional method focusing too much on the form,while the modern method may neglect the consolidation of basic knowledge and personalized needs.Effective strategies for university students are proposed,including classroom teaching,personalised instruction and practical activities.In classroom teaching,writing tasks with practical application scenarios are designed and diversified teaching methods are used.In personalised instruction,students’needs are understood and targeted instruction is provided.In practical activities,diverse writing tasks are designed and effective feedback mechanisms are established.Finally,the contributions of the study and future research directions are summarised.
基金the National Natural Science Foundation of China(Nos.91646205 and 71421002)the Fundamental Research Funds for the Central Universities(No.16JCCS08)。
文摘Although the development of national conditions and the increase in health risk factors undoubtedly pose a huge challenge to China’s medical health and labour security system,these simultaneously promote the elevation and transformation of national healthcare consciousness.Given that the current disease diagnosis and treatment models hardly satisfy the growing demand for medical and health care in China,based on the theory of healthcare and basic laws of human physiological activities,and combined with the characteristics of the information society,this paper presents a panoramic and personalised intelligent healthcare mode that is aimed at improving and promoting individual health.The basic definition and conceptual model are provided,and its basic characteristics and specific connotations are elaborated in detail.Subsequently,an intelligent coordination model of daily time allocation and a dynamic optimisation model for healthcare programmes are proposed.The implementation of this mode is explicitly illustrated with a practical application case.It is expected that this study will provide new ideas for further healthcare research and development.
文摘Radiology（imaging） and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations（phenotypes） to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype（to obtain genomic information） of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography（CT）, magnetic resonance imaging（MRI）, and positron-emission tomography（PET）, the challenges we are facing, and the potential contribution of radiomics towards precision medicine.
文摘Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked- with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator(RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine(or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among the general population. All of the above techniques for addressing bone defects are discussed in this paper.
文摘Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control.Despite the prevalence of diabetes in patients admitted to hospital and intensive care units,the ideal management of hyperglycaemia in these groups is uncertain.There are data that suggest that acute hyperglycaemia in critically ill patients without diabetes is associated with increased mortality and morbidity.Exogenous insulin to keep blood glucose concentrations < 10 mmol/L is accepted as standard of care in this group.However,preliminary data have recently been reported that suggest that chronic hyperglycaemia may result in conditioning,which protects these patients against damage mediated by acute hyperglycaemia.Furthermore,acute glucose-lowering to < 10 mmol/L in patients with diabetes with inadequate glycaemic control prior to their critical illness appears to have the capacity to cause harm.This review focuses on glycaemic control in critically ill patients with type 2 diabetes,the potential for harm from glucose-lowering and the rationale for personalised therapy.
基金Supported by Grants from the Breast Cancer Hope Foundation(London,United Kingdom)
文摘Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor(ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.
基金the National Key Research and Development Program of China(No.2016YFC1100600)the Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine(No.DLY201506)+1 种基金the National Natural Science Foundation of China(Nos.81972058,and 81902194)the Multidisciplinary Team Clinical Research Project of Shanghai Ninth People’s Hospital(No.201701003)。
文摘In this paper,we describe the design and surgical process of personalised pelvic prostheses fixation through 3D printing according to different Enneking pelvic tumour zones:the ilium(Zone I),acetabulum(Zone II),and pubis and ischium(Zone III).A 3D model of the pelvis was reconstructed using imaging data,and the parameters on the planes of the acetabulum and pelvic incisal margin were measured.The main body of the pelvic prosthesis was constructed,a porous structure was designed on the bone-prosthesis interface,and the movement paths,lengths,and diameters of screws were planned.By combining the pathological model and osteotomy guide,limb salvage reconstruction was performed in patients with pelvic tumours.Preoperative and postoperative data were compared to verify the prosthesis stability.Our investigation revealed that the long-term survival of pelvic reconstruction prostheses depends on accurate matching with the bone defect area,good initial stability,and a porous structure to allow bone ingrowth.
基金the National Natural Science Foundation of China(Nos.81772425,31771017,and 31972924)the Project of Science and Technology Commission of Shanghai Municipality(No.16441908700)+2 种基金the Innovation Research Plan of Shanghai Municipal Education Commission(No.ZXWF082101)the National Key Research and Development Program of China(Nos.2017YFC0110700,and 2019YFC0120600)the Interdisciplinary Program of Shanghai Jiao Tong University(Nos.YG2016MS11,JYYQ201516,YG2017MS09,and ZH2018QNA06)。
文摘This study was aimed at comparing the biomechanical performance of personalised 3D-printed clavicle plates of different materials to treat midshaft clavicle fractures with the finite element(FE)method.The FE model of a fractured clavicle with a personalised 3D-printed clavicle plate and screws was constructed.Three types of materials were simulated,including stainless steel,titanium alloy,and magnesium alloy.Two loading conditions(axial compression and inferior bending)were applied at the distal end of the clavicle to simulate arm abduction.Plate stiffness,peak stress,and bone strain at the clavicle fracture site were measured and compared.The stiffness of the stainless steel clavicle plate was significantly greater than that of the titanium alloy clavicle plate.The stiffness of the magnesium alloy clavicle plate was similar to that of the intact clavicle;peak stress of the magnesium alloy clavicle plate was the lowest;thus,it had less stress-shielding effects on bone formation.The magnesium alloy clavicle plate was more likely to form bone by distributing proper strain at the clavicle fracture site.According to the influence of different materials on the tensile strength,magnesium alloy clavicle plates might be preferred owing to their bionic stiffness in the treatment of patients with a low risk of falling.For patients who engage in contact sports,a titanium alloy clavicle plate might be more suitable.
基金the Class IV Peak Discipline Project of Shanghai Jiao Tong University School of Medicine-“3D Snowball”Project(No.Ggxq03)the Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYLJ015)+1 种基金the Clinical Research Plan of SHDC(No.16CR3099B)the National Key Research and Development Program of China(No.2016YFC1102104)。
文摘In our case,3D printing was used to fabricate a custom-made titanium alloy total talar prosthesis as a mirror image of the contralateral healthy talus for a 16-year-old girl who underwent right talar resection for a recurrent giant cell tumour(GCT)of the talus.A porous surface was used over the neck and tail of the talus prosthesis to promote soft tissue attachment and improve the stability of the prosthesis.Pre-drilled medial and lateral holes were prepared for ligament repair and attachment.Eighteen months after the operation,there was no tumour recurrence,and the patient walked without symptoms.The Musculoskeletal Tumour Society score was 22/30,the American Orthopaedic Foot and Ankle Society score was 88/100,and the prosthesis was well positioned on radiographs.The short-and medium-term outcomes indicated that 3D-printed modular talar prostheses could be an effective treatment option.
基金This study was supported by Singapore Health Services Pte Ltd.Prof Ecosse L.Lamoureux received the funding under the SingHealth Research Strategic Hires Scheme,STH-1202-SERI.The grant body had no roles in design,conduct or data analysis of the study.
文摘Background:Using a pilot randomised controlled trial(RCT),to assess the short-term effectiveness of a structured diabetic retinopathy(DR)-specific,intensive,and personalised care planning(DR-IPCP)intervention on diabetes control outcomes in Singaporeans with poorly controlled type 2 diabetes.Methods:Eighteen individuals with mild-moderate DR and poor glycemic control[HbA1c≥64 mmol/mol(≥8.0%)over two consecutive 6-month readings]were randomized to DR-IPCP(n=9)or usual care(UC,n=9).The intervention included a physician consultation,an initial personalised eye consultation with a experienced diabetes nurse educator,and three behaviour change follow-up calls.HbA1c(primary outcome),lipids and blood pressure were assessed at baseline and three months post-intervention.Participant feedback regarding the DR-IPCP program was collected at three months via a semi-structured telephone interview.Results:While no significant between-group differences were observed,DR-IPCP participants experienced significant within-group reductions in HbA1c,total cholesterol,and low density lipoprotein at follow-up compared to baseline[7 mmol/mol(−0.8%),−0.64 mmol/L,and−0.66 mmol/L,respectively].No significant within-group changes in these parameters were observed in the UC group.Following the DR-IPCP intervention,participants reported a clearer understanding of the link between diabetes management;the development and progression of DR.Conclusions:DR-IPCP provides an effective short-term improvement in diabetes control parameters in DR patients with poor diabetes control.An adequately powered and longitudinal RCT is warranted to assess the clinical,patient-centred and economic potential of this programme in this population.
文摘Existing examinations in postgraduate education and continuing medical education (CME) are not perfect. Modern assessment does not reflect disadvantages of older responders, for whom more time for reply is needed. Specialists with wide clinical experience may choose more than one correct answer in alternative questions. Reduced ability to remember in older people restricts examination without additional sources of information. We offer an individualised system for testing doctors. It provides personalised choice of examination questions using multiple choice questions with weight characteristics and absence of distractors, interactive cooperation in case of negative answers and the final decision of an expert in relation to the person tested. A special algorithm is proposed for typical questions that combines the advantages of known approaches to testing. The questioning system is complex for the creators of tests, but is more convenient and objective than existing ones for medical doctors.
基金supported by the National Institute for Health and Care Research(NIHR)Newcastle Biomedical Research Centre(BRC)based at the Newcastle upon Tyne Hospitals NHS Foundation Trust,Newcastle Universitythe Cumbria,Northumberland,and Tyne and Wear(CNTW)NHS Foundation Trust.
文摘Epilepsy is one of the most common neurological disorders,affecting more than 50 million people worldwide.Management is particularly complex in individuals with intellectual disabilities,who are at a much higher risk of having severe seizures compared to the general population.People with intellectual disabilities are regularly excluded from epilepsy research,despite having significantly higher risks of negative health outcomes and early mortality.Recent advances in artificial intelligence(AI)have shown great potential in improving the diagnosis,monitoring,and management of epilepsy.Machine learning techniques have been used in analysing electroencephalography data for efficient seizure detection and prediction,as well as individualised treatment,which facilitates timely and customised intervention for individuals with epilepsy.Research and implementation of AI-based solutions for people with intellectual disabilities and epilepsy still remains limited due to a lack of accessible long-term clinical data for model training,difficulties in communicating with people with intellectual disabilities,and ethical challenges in ensuring the safety of the AI systems for this population.This paper presents an overview of recent AI applications in epilepsy and for people with intellectual disabilities,highlighting key challenges and the necessity of including people with intellectual disabilities in research on AI and epilepsy,and potential strategies to promote the development and use of AI applications for this vulnerable population.Given the prevalence and consequences associated with epilepsy in people with intellectual disabilities,the application of AI in epilepsy care has the potential to have a significant positive impact.To achieve this impact and to avoid increasing existing health inequity,there is an urgent need for greater inclusion of people with intellectual disabilities in research around the application of AI to epilepsy care and management.
文摘The gender-affirmative model of care has proven unsuccessful in many cases of gender dysphoria.There is a pressing need to continue research and develop and implement alternative models of care.Personalised models of care need to replace the standardised ones to reflect the unique nature of internal issues that exist within every individual.A holistic care model that includes Physical,Mental,Emotional,Social,and Spiritual(PMESS)aspects of a person’s wellbeing indicates an effective way forward.Such a multidimensional model enables a greater understanding of complex relationships between different factors and their effects on health and overall wellbeing.Empowered by intelligent technologies,such as data mining and Artificial Intelligence(AI),the PMESS model can systematically capture,analyse,and evaluate data across the multiple dimensions of the holistic model of care.It can help identify patterns within the data,generate useful insights,and support the development of effective prevention and personalized treatment strategies.The PMESS-AI model supports the collaboration between multiple stakeholders,and the machine learning aspects of it can usher in the discovery of new knowledge and breakthroughs in research.
文摘Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis.In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment.Finally,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.
文摘The European Society for Organ Transplantation(ESOT)has created a consensus platform for evidence-based and best-practice recommendations.At the 2022 ESOT consensus conference,nine topics were chosen for further exploration based on their potential for impact on healthcare,existing research gaps,and incomplete coverage of the topic in current scientific literature(1).Among these topics,molecular biology testing for non-invasive diagnosis of allograft rejection was a focal point,as detailed in the ESOT consensus statement on biomarkers in liver transplantation(LT)(2).We extend our congratulations to the authors of the liver subgroup on their dedicated effort and rigorous approach in translating major unmet clinical needs into four well-defined questions of interest regarding biomarkers for prediction and/or diagnosis of longer-term complications after LT.
