Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata...Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
Purpose:To explore the application effect of the cultivation mode of Curriculum Ideology and Political Integration of Medical Humanities to enhance the core values of medicine in the clinical internship stage of medic...Purpose:To explore the application effect of the cultivation mode of Curriculum Ideology and Political Integration of Medical Humanities to enhance the core values of medicine in the clinical internship stage of medical students.Methods:Students in the clinical internship stage of the First Affiliated Hospital of Baotou Medical College were selected,and a total of 156 students in one random class in each grade were taken as the observation group and received the integration cultivation mode;148 students were taken as the control group and employed the traditional mode.The teaching effect of interns in the two groups was analyzed.Results:The teaching performance of students in both groups after clinical internship teaching was improved compared with that before admission;the teaching performance,teaching effect,teaching evaluation,and teaching satisfaction of the observation group were higher than that of the control group.Conclusion:The integration of the medical humanities training model with curriculum ideology and politics in the clinical internship of medical students is conducive to the improvement of teaching performance,teaching evaluation,teaching satisfaction of teachers and students,and the development and improvement of core values of medical students,which is of good value for teaching application.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis...BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.展开更多
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
To conform to the college English teaching reform from English for General Purposes (EGP) to English for Academic Purposes (EAP) in the vital transfer era, the Foreign Language Department of Second Military Medical Un...To conform to the college English teaching reform from English for General Purposes (EGP) to English for Academic Purposes (EAP) in the vital transfer era, the Foreign Language Department of Second Military Medical University (SMMU) launched an English for Medical Academic Purpose (EMAP) curriculum with English Forum on Medical Humanities (EFMH), a project-based teaching practice. Based on Rogers' learner-centered humanistic teaching approach which emphasizes students' involvement and experiences in learning, EFMH puts students and their practice in a central place. After four-year exploration and operation, the Forum has developed from a small-scaled embryo into an internationalized, standardized and professionalized event, having produced fruitful outcomes. It is expected that the success of EFMH will provide inspiring experiences and enlightenments for higher medical education in terms of academic English teaching and teachers' responsibilities to foster high-quality medical students.展开更多
The emergence of "Big Data" has been a dramatic development in recent years. Alongside it, a lesser-known but equally important set of concepts and practices has also come into being--"Smart Data." This paper shar...The emergence of "Big Data" has been a dramatic development in recent years. Alongside it, a lesser-known but equally important set of concepts and practices has also come into being--"Smart Data." This paper shares the author's understanding of what, why, how, who, where, and which data in relation to Smart Data and digital humanities. It concludes that, challenges and opportunities co-exist, but it is certain that Smart Data, the ability to achieve big insights from trusted, contextualized, relevant, cognitive, predictive, and consumable data at any scale, will continue to have extraordinary value in digital humanities.展开更多
Humanities and Social Sciences(HSS) are undergoing the transformation of spatialization and quantification. Geo-computation, with geoinformatics(including RS: Remote Sensing;GIS: Geographical Information System;GNSS: ...Humanities and Social Sciences(HSS) are undergoing the transformation of spatialization and quantification. Geo-computation, with geoinformatics(including RS: Remote Sensing;GIS: Geographical Information System;GNSS: Global Navigation Satellite System), provides effective computational and spatialization methods and tools for HSS. Spatial Humanities and Geo-computation for Social Sciences(SH&GSS) is a field coupling geo-computation, and geoinformatics, with HSS. This special issue accepted a set of contributions highlighting recent advances in methodologies and applications of SH&GSS, which are related to sentiment spatial analysis from social media data, emotional change spatial analysis from news data, spatial analysis of social media related to COVID-19, crime spatiotemporal analysis, “double evaluation” for Land Use/Land Cover(LUCC), Specially Protected Natural Areas(SPNA) analysis, editing behavior analysis of Volunteered Geographic Information(VGI), electricity consumption anomaly detection, First and Last Mile Problem(FLMP) of public transport, and spatial interaction network analysis for crude oil trade network. Based on these related researches, we aim to present an overview of SH&GSS, and propose some future research directions for SH&HSS.展开更多
Dickens, a great realist novelist in his time, captured the popularity as no other novelist had done. And Oliver Twist,one of his successful works, greatly displays his genius in the novel. Oliver is a perfect figure ...Dickens, a great realist novelist in his time, captured the popularity as no other novelist had done. And Oliver Twist,one of his successful works, greatly displays his genius in the novel. Oliver is a perfect figure created by Dickens. In this paper, we will discuss the humanities by analyzing Oliver's personality and thus build a better understanding of the novel and the great writer Dickens.展开更多
At this point in time,the importance of medical humanities education has not been fully understood during the standardized training of residents in China.The study of medical humanities is an important facet of ophtha...At this point in time,the importance of medical humanities education has not been fully understood during the standardized training of residents in China.The study of medical humanities is an important facet of ophthalmology residency that needs to be strengthened.During the standardized training of ophthalmology residents,not only the medical sciences should be strengthened,but also the nature and practice of medical humanities knowledge should be enhanced in multiple aspects.Offering medically-relevant literature,history,philosophy and other courses,simulating real medical activities,being enthusiastic in popular medical science and increasing the contents of the examination in medical humanities would all be areas that would further advance the ophthalmology residency.Along with medical science education,residents will be led and trained on medical humanities as to build good medical humanistic spirit of patient care so that they may better serve patients.展开更多
Purpose: To present a method for systematically mapping diversity of publication patterns at the author level in the social sciences and humanities in terms of publication type, publication language and co-authorship....Purpose: To present a method for systematically mapping diversity of publication patterns at the author level in the social sciences and humanities in terms of publication type, publication language and co-authorship.Design/methodology/approach: In a follow-up to the hard partitioning clustering by Verleysen and Weeren in 2016, we now propose the complementary use of fuzzy cluster analysis, making use of a membership coefficient to study gradual differences between publication styles among authors within a scholarly discipline. The analysis of the probability density function of the membership coefficient allows to assess the distribution of publication styles within and between disciplines.Findings: As an illustration we analyze 1,828 productive authors affiliated in Flanders, Belgium. Whereas a hard partitioning previously identified two broad publication styles, an international one vs. a domestic one, fuzzy analysis now shows gradual differences among authors. Internal diversity also varies across disciplines and can be explained by researchers’ specialization and dissemination strategies.Research limitations: The dataset used is limited to one country for the years 2000–2011; a cognitive classification of authors may yield a different result from the affiliation-based classification used here.Practical implications: Our method is applicable to other bibliometric and research evaluation contexts, especially for the social sciences and humanities in non-Anglophone countries.Originality/value: The method proposed is a novel application of cluster analysis to the field of bibliometrics. Applied to publication patterns at the author level in the social sciences and humanities, for the first time it systematically documents intra-disciplinary diversity.展开更多
BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of canc...BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.展开更多
To improve high quality and/or retain achieved high quality of an academic program, time to time evaluation for quality of each covered course is often an integrated aspect considered in reputed institutions, however,...To improve high quality and/or retain achieved high quality of an academic program, time to time evaluation for quality of each covered course is often an integrated aspect considered in reputed institutions, however, there has been little effort regarding humanities courses. This research article deals with analysis of evaluation data collected regarding humanities course from a College of Commerce & Economics, Mumbai, Maharashtra, India, on Likert type items. Appropriateness of one parametric measure and three non-parametric measures are discussed and used in this regard which could provide useful clues for educational policy planners. Keeping in view of the analytical results using these four measures, regardless of the threshold regarding satisfaction among students, overall performance of almost every subject has been un-satisfactory. There is a need to make a focused approach to take every course at the level of high performance. The inconsistency noticed under every threshold further revealed that under such poorly performing subjects globally, one needs to analyze merely at the global level item. Once the global level analysis reveals high performance of a course, then only item specific analysis may need to be focused to find out the items requiring further improvements.展开更多
Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogene...Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.展开更多
文摘Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金Ideological and Political Project of Scientific Research Fund of Baotou Medical College(BYJJ-SZZX 202303)。
文摘Purpose:To explore the application effect of the cultivation mode of Curriculum Ideology and Political Integration of Medical Humanities to enhance the core values of medicine in the clinical internship stage of medical students.Methods:Students in the clinical internship stage of the First Affiliated Hospital of Baotou Medical College were selected,and a total of 156 students in one random class in each grade were taken as the observation group and received the integration cultivation mode;148 students were taken as the control group and employed the traditional mode.The teaching effect of interns in the two groups was analyzed.Results:The teaching performance of students in both groups after clinical internship teaching was improved compared with that before admission;the teaching performance,teaching effect,teaching evaluation,and teaching satisfaction of the observation group were higher than that of the control group.Conclusion:The integration of the medical humanities training model with curriculum ideology and politics in the clinical internship of medical students is conducive to the improvement of teaching performance,teaching evaluation,teaching satisfaction of teachers and students,and the development and improvement of core values of medical students,which is of good value for teaching application.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
基金Supported by the National Research Foundation of Korea,No.2020R1A2C1100891Soonchunhyang University Research Fund,No.2024-05-014.
文摘BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
文摘To conform to the college English teaching reform from English for General Purposes (EGP) to English for Academic Purposes (EAP) in the vital transfer era, the Foreign Language Department of Second Military Medical University (SMMU) launched an English for Medical Academic Purpose (EMAP) curriculum with English Forum on Medical Humanities (EFMH), a project-based teaching practice. Based on Rogers' learner-centered humanistic teaching approach which emphasizes students' involvement and experiences in learning, EFMH puts students and their practice in a central place. After four-year exploration and operation, the Forum has developed from a small-scaled embryo into an internationalized, standardized and professionalized event, having produced fruitful outcomes. It is expected that the success of EFMH will provide inspiring experiences and enlightenments for higher medical education in terms of academic English teaching and teachers' responsibilities to foster high-quality medical students.
文摘The emergence of "Big Data" has been a dramatic development in recent years. Alongside it, a lesser-known but equally important set of concepts and practices has also come into being--"Smart Data." This paper shares the author's understanding of what, why, how, who, where, and which data in relation to Smart Data and digital humanities. It concludes that, challenges and opportunities co-exist, but it is certain that Smart Data, the ability to achieve big insights from trusted, contextualized, relevant, cognitive, predictive, and consumable data at any scale, will continue to have extraordinary value in digital humanities.
基金National Natural Science Foundation of China(No.42171448)。
文摘Humanities and Social Sciences(HSS) are undergoing the transformation of spatialization and quantification. Geo-computation, with geoinformatics(including RS: Remote Sensing;GIS: Geographical Information System;GNSS: Global Navigation Satellite System), provides effective computational and spatialization methods and tools for HSS. Spatial Humanities and Geo-computation for Social Sciences(SH&GSS) is a field coupling geo-computation, and geoinformatics, with HSS. This special issue accepted a set of contributions highlighting recent advances in methodologies and applications of SH&GSS, which are related to sentiment spatial analysis from social media data, emotional change spatial analysis from news data, spatial analysis of social media related to COVID-19, crime spatiotemporal analysis, “double evaluation” for Land Use/Land Cover(LUCC), Specially Protected Natural Areas(SPNA) analysis, editing behavior analysis of Volunteered Geographic Information(VGI), electricity consumption anomaly detection, First and Last Mile Problem(FLMP) of public transport, and spatial interaction network analysis for crude oil trade network. Based on these related researches, we aim to present an overview of SH&GSS, and propose some future research directions for SH&HSS.
文摘Dickens, a great realist novelist in his time, captured the popularity as no other novelist had done. And Oliver Twist,one of his successful works, greatly displays his genius in the novel. Oliver is a perfect figure created by Dickens. In this paper, we will discuss the humanities by analyzing Oliver's personality and thus build a better understanding of the novel and the great writer Dickens.
文摘At this point in time,the importance of medical humanities education has not been fully understood during the standardized training of residents in China.The study of medical humanities is an important facet of ophthalmology residency that needs to be strengthened.During the standardized training of ophthalmology residents,not only the medical sciences should be strengthened,but also the nature and practice of medical humanities knowledge should be enhanced in multiple aspects.Offering medically-relevant literature,history,philosophy and other courses,simulating real medical activities,being enthusiastic in popular medical science and increasing the contents of the examination in medical humanities would all be areas that would further advance the ophthalmology residency.Along with medical science education,residents will be led and trained on medical humanities as to build good medical humanistic spirit of patient care so that they may better serve patients.
文摘Purpose: To present a method for systematically mapping diversity of publication patterns at the author level in the social sciences and humanities in terms of publication type, publication language and co-authorship.Design/methodology/approach: In a follow-up to the hard partitioning clustering by Verleysen and Weeren in 2016, we now propose the complementary use of fuzzy cluster analysis, making use of a membership coefficient to study gradual differences between publication styles among authors within a scholarly discipline. The analysis of the probability density function of the membership coefficient allows to assess the distribution of publication styles within and between disciplines.Findings: As an illustration we analyze 1,828 productive authors affiliated in Flanders, Belgium. Whereas a hard partitioning previously identified two broad publication styles, an international one vs. a domestic one, fuzzy analysis now shows gradual differences among authors. Internal diversity also varies across disciplines and can be explained by researchers’ specialization and dissemination strategies.Research limitations: The dataset used is limited to one country for the years 2000–2011; a cognitive classification of authors may yield a different result from the affiliation-based classification used here.Practical implications: Our method is applicable to other bibliometric and research evaluation contexts, especially for the social sciences and humanities in non-Anglophone countries.Originality/value: The method proposed is a novel application of cluster analysis to the field of bibliometrics. Applied to publication patterns at the author level in the social sciences and humanities, for the first time it systematically documents intra-disciplinary diversity.
基金Supported by National Natural Science Foundation of China,No.82360329Inner Mongolia Medical University General Project,No.YKD2023MS047Inner Mongolia Health Commission Science and Technology Plan Project,No.202201275.
文摘BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
文摘To improve high quality and/or retain achieved high quality of an academic program, time to time evaluation for quality of each covered course is often an integrated aspect considered in reputed institutions, however, there has been little effort regarding humanities courses. This research article deals with analysis of evaluation data collected regarding humanities course from a College of Commerce & Economics, Mumbai, Maharashtra, India, on Likert type items. Appropriateness of one parametric measure and three non-parametric measures are discussed and used in this regard which could provide useful clues for educational policy planners. Keeping in view of the analytical results using these four measures, regardless of the threshold regarding satisfaction among students, overall performance of almost every subject has been un-satisfactory. There is a need to make a focused approach to take every course at the level of high performance. The inconsistency noticed under every threshold further revealed that under such poorly performing subjects globally, one needs to analyze merely at the global level item. Once the global level analysis reveals high performance of a course, then only item specific analysis may need to be focused to find out the items requiring further improvements.
基金the National Natural Science Foundation of China,No.82360148Guizhou Science&Technology Department,No.QKHPTRC2018-5636-2 and No.QKHPTRC2020-2201.
文摘Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.