BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains un...BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains unclear.AIM To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival.METHODS Immunohistochemical analysis of CLDN6 expression was performed on formalinfixed,paraffin-embedded tissues from 80 patients diagnosed with HGEC.Associations between CLDN6 expression and histological subtype,the International Federation of Gynecology and Obstetrics(FIGO)stage,depth of myometrial invasion,lymphovascular space invasion,recurrence,and survival outcomes were statistically analysed.Univariate and multivariate Cox regression models were used to identify independent prognostic factors.RESULTS High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology(P=0.026),advanced FIGO stage(P=0.015),deep myometrial invasion(P=0.038),and recurrence(P=0.002).While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group,multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival[hazard ratio(HR)=68.98,P=0.022]and overall survival(HR=24.023,P=0.038).CONCLUSION CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC,suggesting its utility as a prognostic biomarker and potential therapeutic target.展开更多
High-grade dysplasia(HGD) in Barrett's esophagus(BE) is the critical step before invasive esophageal adenocarcinoma.Although its natural history remains unclear,an aggressive therapeutic approach is usually indica...High-grade dysplasia(HGD) in Barrett's esophagus(BE) is the critical step before invasive esophageal adenocarcinoma.Although its natural history remains unclear,an aggressive therapeutic approach is usually indicated.Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium.In healthy patients with reasonable life expectancy,vagal-sparing esophagectomy,with associated low mortality and low early and late postoperative morbidity,is considered the treatment of choice for BE with HGD.Patients unfit for surgery should be managed in a less aggressive manner,using endoscopic ablation or endoscopic mucosal resection of the entire BE segment,followed by lifelong surveillance.Patients eligible for surgery who present with a long BE segment,multifocal dysplastic lesions,severe reflux symptoms,a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment,either surgical or endoscopic.展开更多
BACKGROUND High-grade aneurysmal subarachnoid hemorrhage is a devastating disease with a low favorable outcome.Elevated intracranial pressure is a substantial feature of high-grade aneurysmal subarachnoid hemorrhage t...BACKGROUND High-grade aneurysmal subarachnoid hemorrhage is a devastating disease with a low favorable outcome.Elevated intracranial pressure is a substantial feature of high-grade aneurysmal subarachnoid hemorrhage that can result to secondary brain injury.Early control of intracranial pressure including decompressive craniectomy and external ventricular drainage had been reported to be associated with improved outcomes.But in recent years,little is known whether external ventricular drainage and intracranial pressure monitoring after coiling could improve outcomes in high-grade aneurysmal subarachnoid hemorrhage.AIM To investigate the outcomes of high-grade aneurysmal subarachnoid hemorrhage patients with coiling and ventricular intracranial pressure monitoring.METHODS A retrospective analysis of a consecutive series of high-grade patients treated between Jan 2016 and Jun 2017 was performed.In our center,followed by continuous intracranial pressure monitoring,the use of ventricular pressure probe for endovascular coiling and invasive intracranial pressure monitoring in the acute phase is considered to be the first choice for the treatment of high-grade patients.We retrospectively analyzed patient characteristics,radiological features,intracranial pressure monitoring parameters,complications,mortality and outcome.RESULTS A total of 36 patients were included,and 32(88.89%)survived.The overall mortality rate was 11.11%.No patient suffered from aneurysm re-rupture.The intracranial pressure in 33 patients(91.67%)was maintained within the normal range by ventricular drainage during the treatment.A favorable outcome was achieved in 18 patients(50%)with 6 mo follow-up.Delayed cerebral ischemia and Glasgow coma scale were considered as significant predictors of outcome(2.066 and-0.296,respectively,P<0.05).CONCLUSION Ventricular intracranial pressure monitoring may effectively maintain the intracranial pressure within the normal range.Despite the small number of cases in the current work,high-grade patients may benefit from a combination therapy of early coiling and subsequent ventricular intracranial pressure monitoring.展开更多
High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatograph...High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.展开更多
Myofibroblastic sarcoma(MS)is a rare malignant soft tissue tumor characterized by myofibroblasts.It most commonly arises in the head and neck region,especially the tongue,with rare occurrences in the limbs.MS exhibits...Myofibroblastic sarcoma(MS)is a rare malignant soft tissue tumor characterized by myofibroblasts.It most commonly arises in the head and neck region,especially the tongue,with rare occurrences in the limbs.MS exhibits varying histopathology,ranging from low-to high-grade,with diverse subtypes showing different clinical behaviors and prognoses.This article reports the first case of high-grade MS in the hand,adding to the limited documentation of this rare condition.Here,we present the case of a 30-year-old healthy female with a year-long history of progressive shortening,mobility loss,and weakness in the first finger of the left hand.Left-hand imaging revealed a lytic,cottony tumor involving the entire first metacarpal.Following surgical resection,which included metatarsal grafting and joint reconstruction,a diagnosis of high-grade MS was confirmed based on histological manifestations and immunohistochemical staining,which was further classified as grade 2 according to the French Federation of Cancer Centers Sarcoma Group system.Postoperative radiotherapy was administered and the patient experienced a successful recovery without graft osteonecrosis.The patient regained 90%mobility and strength,without shortening,after surgical resection and radiotherapy.Six months post-surgery,the patient reported full hand functionality.MS is a rare tumor that infrequently affects bones and is often misdiagnosed owing to its controversial characteristics.The initial treatment should focus on complete resection with negative margins,followed by reconstructive surgery to preserve function.Further case studies are needed to establish standardized surgical treatment protocols.展开更多
Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,techno...Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.展开更多
The superconducting high gradient magnetic separation(S-HGMS)technology can be used to effectively extract silica from iron ore tailings(IOTs).However,particle agglomeration in strong magnetic fields poses a challenge...The superconducting high gradient magnetic separation(S-HGMS)technology can be used to effectively extract silica from iron ore tailings(IOTs).However,particle agglomeration in strong magnetic fields poses a challenge in achieving optimal performance.In this study,we investigated the agglomeration of IOT particles and the mechanisms for its inhibition through surface analysis,density functional theory(DFT),and extended Derjaguin-Landau-Verwey-Overbeek(EDLVO)theory.Hematite was found to exhibit the highest magnetic moment among the minerals present in IOTs,making it particularly prone to magnetic agglomeration.The addition of the dispersant SDSH into the slurry was essential in promoting the dispersion of IOT particles during the S-HGMS process.This dispersant hydrolyzed to form HPO_(4)^(2-)and RSO_(3)^(-)groups in the solution,which then chemically adsorbed onto the metal ions exposed on the surfaces of non-quartz particles,increasing interparticle electrostatic repulsion.Furthermore,the RSO_(3)^(-)groups physically adsorbed onto the surface of quartz particles,resulting in strong steric repulsion and enhancing the hydrophilicity of the particle surfaces,thereby inhibiting magnetic agglomeration between the particles.Under optimal conditions,the SiO_(2)grade of the obtained high-grade silica powder increased from an initial value of 76.32%in IOTs to 97.42%,achieving a SiO_(2)recovery rate of 54.81%,which meets the requirements for quartz sand used in glass preparation.This study provides valuable insights into the magnetic agglomeration of IOT particles and its inhibition while providing a foundation for regulating S-HGMS processes.展开更多
BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,...BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,particularly for diagnostic support,offering real-time insights into complex conditions such as esophageal squamous cell carcinoma.CASE SUMMARY In this study,we introduce a multimodal AI system that successfully identified and delineated a small and flat carcinoma during esophagogastroduodenoscopy,highlighting its potential for early detection of malignancies.The lesion was confirmed as high-grade squamous intraepithelial neoplasia,with pathology results supporting the AI system’s accuracy.The multimodal AI system offers an integrated solution that provides real-time,accurate diagnostic information directly within the endoscopic device interface,allowing for single-monitor use without disrupting endoscopist’s workflow.CONCLUSION This work underscores the transformative potential of AI to enhance endoscopic diagnosis by enabling earlier,more accurate interventions.展开更多
BACKGROUND High-grade serous ovarian carcinoma(HGSOC)is among the most lethal gynecological malignancies,characterized by late-stage diagnosis,extensive peritoneal dissemination,and limited treatment options,resulting...BACKGROUND High-grade serous ovarian carcinoma(HGSOC)is among the most lethal gynecological malignancies,characterized by late-stage diagnosis,extensive peritoneal dissemination,and limited treatment options,resulting in poor survival outcomes.The tumor microenvironment plays a critical role in disease progression and therapy resistance,with CD4+T cells exhibiting significant plasticity and functional heterogeneity.Regulatory T cells(Tregs)are particularly implicated in immune suppression and tumor evasion.However,the spatial distribution,functional states,and prognostic significance of CD4+T cell subtypes in HGSOC remain poorly understood.AIM To characterize the functional heterogeneity and tissue-specific distributions of CD4+T cell subtypes in HGSOC and identify biomarkers for therapy.METHODS We analyzed single-cell RNA sequencing(scRNA-seq)data from 42 HGSOC patients,examining samples collected from adnexal tissues and ascites.CD4+T cells were identified and classified into subtypes using unsupervised clustering and marker gene analysis.Functional profiling was performed using pathway enrichment,differential expression analysis,and functional signature scoring.Kaplan-Meier survival and Cox proportional hazards modeling were conducted to evaluate the prognostic value of CD4+T cell subtypes.RESULTS Distinct distributions of CD4+T cell subtypes were identified between adnexal tissues and ascites.Naive CD4+T cells were predominant in ascites,while Tregs and CXCL13-expressing CD4+T cells were enriched in adnexal tissues.Tregs were further categorized into four subtypes(Treg1,Treg2,Treg3,and TISG),each exhibiting unique molecular signatures and tissue-specific adaptations.Treg3 cells,enriched in adnexal tissues,were characterized by high levels of activation and exhaustion markers,correlating with poor clinical outcomes in HGSOC patients.CONCLUSION Treg3 cells drive immune suppression and tumor progression in HGSOC,making them a key immunotherapy target.Their adnexal enrichment highlights the need for tissue-specific immune profiling in precision treatment.展开更多
The Triassic Xujiahe Formation in the slope zone of the Sichuan foreland basin is a new field of continental tight gas exploration in recent years.The fourth member of the Xujiahe Formation(Xu4 Member),the major inter...The Triassic Xujiahe Formation in the slope zone of the Sichuan foreland basin is a new field of continental tight gas exploration in recent years.The fourth member of the Xujiahe Formation(Xu4 Member),the major interval in the Jianyang Block of the Tianfu gas field in the basin,is characterized by considerable buried depth,tight reservoirs,and strong heterogeneity.By using cast thin section,X-ray diffraction(XRD),scanning electron microscopy(SEM),fluid inclusion thermometry,and core analysis,the reservoir rock types,dominant diageneses,diagenetic history,and controls on high-graded reservoirs were investigated.It is found that the Xu4 Member in Jianyang mainly consists of lithic feldspar sandstones and feldspar lithic sandstones,followed by lithic quartz sandstones.High-energy hydrodynamic conditions in the microfacies of underwater distributary channels and mouth bars are beneficial to the preservation of primary pores and the occurrence of secondary pores,and there are no significant differences in petrophysical properties between these two microfacies.Compaction and calcareous cementation are the dominant controls on reservoir porosity decrease in the Xujiahe Formation;corrosion is the major contributor to porosity increase by generating secondary dissolved pores,e.g.intragranular dissolved pores and intergranular dissolved pores,as major reservoir space in the study area.Fracture zones around the faults inside the Xujiahe Formation(fourth‒order faults)are favorable for proximal tight gas accumulation,preservation,and production.The research findings have been successfully applied to explore the Xujiahe Formation in the slope zone of the Sichuan foreland basin.They can be referential for other similar tight sandstone gas accumulations.展开更多
Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the...Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the prognosis of patients with advanced high-grade serous ovarian cancer(HGSOC)remain unclear.Methods:We assessed the percentages of PD-1^(+)and CD57^(+)CD8^(+)T cells in tumor-infiltrating lymphocytes(TILs,n=85)and tumor ascites lymphocytes(TALs,n=87)using flow cytometry.The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method.Gene expression analysis elucidated the tumor immune microenvironment(TIME,n=36).Results:Patients with higher PD-1^(+)CD8^(+)TILs(>87.8%)exhibited longer platinum-free interval(PFI)and overall survival(OS).In contrast,those with elevated CD57^(+)CD8^(+)TALs(>28.69%)were more likely to experience chemotherapy and had lower complete remission rates,shorter PFI and OS.PD-1^(+)CD8^(+)TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities.Approximately 50%of CD57^(+)CD8^(+)TALs were terminally differentiated,exhibiting significantly impaired proliferation.Based on the proportions of PD-1^(+)CD8^(+)TILs and CD57^(+)CD8^(+)TALs,patients were categorized into good,median and poor prognosis groups,with median PFI of 47.78,27.29 and 11.96 months,respectively(P<0.0001).Median OS for these groups was not reach,49.23 and 30.92 months,respectively(P<0.0001).Patients with poor prognosis exhibit significantly reduced CD8^(+)T cell proportion and increased M2 macrophage in the TIME,alongside downregulation of multiple T cell activation-related pathways.Conclusions:Lower levels of PD-1^(+)CD8^(+)TILs and higher CD57^(+)CD8^(+)TALs,assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.展开更多
文摘BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains unclear.AIM To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival.METHODS Immunohistochemical analysis of CLDN6 expression was performed on formalinfixed,paraffin-embedded tissues from 80 patients diagnosed with HGEC.Associations between CLDN6 expression and histological subtype,the International Federation of Gynecology and Obstetrics(FIGO)stage,depth of myometrial invasion,lymphovascular space invasion,recurrence,and survival outcomes were statistically analysed.Univariate and multivariate Cox regression models were used to identify independent prognostic factors.RESULTS High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology(P=0.026),advanced FIGO stage(P=0.015),deep myometrial invasion(P=0.038),and recurrence(P=0.002).While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group,multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival[hazard ratio(HR)=68.98,P=0.022]and overall survival(HR=24.023,P=0.038).CONCLUSION CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC,suggesting its utility as a prognostic biomarker and potential therapeutic target.
文摘High-grade dysplasia(HGD) in Barrett's esophagus(BE) is the critical step before invasive esophageal adenocarcinoma.Although its natural history remains unclear,an aggressive therapeutic approach is usually indicated.Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium.In healthy patients with reasonable life expectancy,vagal-sparing esophagectomy,with associated low mortality and low early and late postoperative morbidity,is considered the treatment of choice for BE with HGD.Patients unfit for surgery should be managed in a less aggressive manner,using endoscopic ablation or endoscopic mucosal resection of the entire BE segment,followed by lifelong surveillance.Patients eligible for surgery who present with a long BE segment,multifocal dysplastic lesions,severe reflux symptoms,a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment,either surgical or endoscopic.
基金Jiangsu Planned Projects for Post-doctoral Research Funds,No.2019k281Jiangsu Natural Science Foundation,No.BK20191231.
文摘BACKGROUND High-grade aneurysmal subarachnoid hemorrhage is a devastating disease with a low favorable outcome.Elevated intracranial pressure is a substantial feature of high-grade aneurysmal subarachnoid hemorrhage that can result to secondary brain injury.Early control of intracranial pressure including decompressive craniectomy and external ventricular drainage had been reported to be associated with improved outcomes.But in recent years,little is known whether external ventricular drainage and intracranial pressure monitoring after coiling could improve outcomes in high-grade aneurysmal subarachnoid hemorrhage.AIM To investigate the outcomes of high-grade aneurysmal subarachnoid hemorrhage patients with coiling and ventricular intracranial pressure monitoring.METHODS A retrospective analysis of a consecutive series of high-grade patients treated between Jan 2016 and Jun 2017 was performed.In our center,followed by continuous intracranial pressure monitoring,the use of ventricular pressure probe for endovascular coiling and invasive intracranial pressure monitoring in the acute phase is considered to be the first choice for the treatment of high-grade patients.We retrospectively analyzed patient characteristics,radiological features,intracranial pressure monitoring parameters,complications,mortality and outcome.RESULTS A total of 36 patients were included,and 32(88.89%)survived.The overall mortality rate was 11.11%.No patient suffered from aneurysm re-rupture.The intracranial pressure in 33 patients(91.67%)was maintained within the normal range by ventricular drainage during the treatment.A favorable outcome was achieved in 18 patients(50%)with 6 mo follow-up.Delayed cerebral ischemia and Glasgow coma scale were considered as significant predictors of outcome(2.066 and-0.296,respectively,P<0.05).CONCLUSION Ventricular intracranial pressure monitoring may effectively maintain the intracranial pressure within the normal range.Despite the small number of cases in the current work,high-grade patients may benefit from a combination therapy of early coiling and subsequent ventricular intracranial pressure monitoring.
文摘High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.
文摘Myofibroblastic sarcoma(MS)is a rare malignant soft tissue tumor characterized by myofibroblasts.It most commonly arises in the head and neck region,especially the tongue,with rare occurrences in the limbs.MS exhibits varying histopathology,ranging from low-to high-grade,with diverse subtypes showing different clinical behaviors and prognoses.This article reports the first case of high-grade MS in the hand,adding to the limited documentation of this rare condition.Here,we present the case of a 30-year-old healthy female with a year-long history of progressive shortening,mobility loss,and weakness in the first finger of the left hand.Left-hand imaging revealed a lytic,cottony tumor involving the entire first metacarpal.Following surgical resection,which included metatarsal grafting and joint reconstruction,a diagnosis of high-grade MS was confirmed based on histological manifestations and immunohistochemical staining,which was further classified as grade 2 according to the French Federation of Cancer Centers Sarcoma Group system.Postoperative radiotherapy was administered and the patient experienced a successful recovery without graft osteonecrosis.The patient regained 90%mobility and strength,without shortening,after surgical resection and radiotherapy.Six months post-surgery,the patient reported full hand functionality.MS is a rare tumor that infrequently affects bones and is often misdiagnosed owing to its controversial characteristics.The initial treatment should focus on complete resection with negative margins,followed by reconstructive surgery to preserve function.Further case studies are needed to establish standardized surgical treatment protocols.
文摘Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.
基金supported by USTB Institute for International People-to-People Exchange in Mining,Metallurgy and Metals Industries(No.FRF-IPPE-2404)Scientific Research Platform Construction Fund for the Introduction of High-Level Talents at Kunming University of Science and Technology(No.CA25073M246A).
文摘The superconducting high gradient magnetic separation(S-HGMS)technology can be used to effectively extract silica from iron ore tailings(IOTs).However,particle agglomeration in strong magnetic fields poses a challenge in achieving optimal performance.In this study,we investigated the agglomeration of IOT particles and the mechanisms for its inhibition through surface analysis,density functional theory(DFT),and extended Derjaguin-Landau-Verwey-Overbeek(EDLVO)theory.Hematite was found to exhibit the highest magnetic moment among the minerals present in IOTs,making it particularly prone to magnetic agglomeration.The addition of the dispersant SDSH into the slurry was essential in promoting the dispersion of IOT particles during the S-HGMS process.This dispersant hydrolyzed to form HPO_(4)^(2-)and RSO_(3)^(-)groups in the solution,which then chemically adsorbed onto the metal ions exposed on the surfaces of non-quartz particles,increasing interparticle electrostatic repulsion.Furthermore,the RSO_(3)^(-)groups physically adsorbed onto the surface of quartz particles,resulting in strong steric repulsion and enhancing the hydrophilicity of the particle surfaces,thereby inhibiting magnetic agglomeration between the particles.Under optimal conditions,the SiO_(2)grade of the obtained high-grade silica powder increased from an initial value of 76.32%in IOTs to 97.42%,achieving a SiO_(2)recovery rate of 54.81%,which meets the requirements for quartz sand used in glass preparation.This study provides valuable insights into the magnetic agglomeration of IOT particles and its inhibition while providing a foundation for regulating S-HGMS processes.
基金Supported by the 135 High-end Talent Project of West China Hospital,Sichuan University,No.ZYDG23029.
文摘BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,particularly for diagnostic support,offering real-time insights into complex conditions such as esophageal squamous cell carcinoma.CASE SUMMARY In this study,we introduce a multimodal AI system that successfully identified and delineated a small and flat carcinoma during esophagogastroduodenoscopy,highlighting its potential for early detection of malignancies.The lesion was confirmed as high-grade squamous intraepithelial neoplasia,with pathology results supporting the AI system’s accuracy.The multimodal AI system offers an integrated solution that provides real-time,accurate diagnostic information directly within the endoscopic device interface,allowing for single-monitor use without disrupting endoscopist’s workflow.CONCLUSION This work underscores the transformative potential of AI to enhance endoscopic diagnosis by enabling earlier,more accurate interventions.
基金Supported by The Natural Science Foundation of Hunan Province,China,No.2022JJ30329.
文摘BACKGROUND High-grade serous ovarian carcinoma(HGSOC)is among the most lethal gynecological malignancies,characterized by late-stage diagnosis,extensive peritoneal dissemination,and limited treatment options,resulting in poor survival outcomes.The tumor microenvironment plays a critical role in disease progression and therapy resistance,with CD4+T cells exhibiting significant plasticity and functional heterogeneity.Regulatory T cells(Tregs)are particularly implicated in immune suppression and tumor evasion.However,the spatial distribution,functional states,and prognostic significance of CD4+T cell subtypes in HGSOC remain poorly understood.AIM To characterize the functional heterogeneity and tissue-specific distributions of CD4+T cell subtypes in HGSOC and identify biomarkers for therapy.METHODS We analyzed single-cell RNA sequencing(scRNA-seq)data from 42 HGSOC patients,examining samples collected from adnexal tissues and ascites.CD4+T cells were identified and classified into subtypes using unsupervised clustering and marker gene analysis.Functional profiling was performed using pathway enrichment,differential expression analysis,and functional signature scoring.Kaplan-Meier survival and Cox proportional hazards modeling were conducted to evaluate the prognostic value of CD4+T cell subtypes.RESULTS Distinct distributions of CD4+T cell subtypes were identified between adnexal tissues and ascites.Naive CD4+T cells were predominant in ascites,while Tregs and CXCL13-expressing CD4+T cells were enriched in adnexal tissues.Tregs were further categorized into four subtypes(Treg1,Treg2,Treg3,and TISG),each exhibiting unique molecular signatures and tissue-specific adaptations.Treg3 cells,enriched in adnexal tissues,were characterized by high levels of activation and exhaustion markers,correlating with poor clinical outcomes in HGSOC patients.CONCLUSION Treg3 cells drive immune suppression and tumor progression in HGSOC,making them a key immunotherapy target.Their adnexal enrichment highlights the need for tissue-specific immune profiling in precision treatment.
基金supported by the China National Petroleum Corporation Science and Technology Project(Study on genesis mechanism and distribution law of high quality reservoir of the fourth Member of Xujiahe Formation in middle and west Sichuan area,20230301-23)。
文摘The Triassic Xujiahe Formation in the slope zone of the Sichuan foreland basin is a new field of continental tight gas exploration in recent years.The fourth member of the Xujiahe Formation(Xu4 Member),the major interval in the Jianyang Block of the Tianfu gas field in the basin,is characterized by considerable buried depth,tight reservoirs,and strong heterogeneity.By using cast thin section,X-ray diffraction(XRD),scanning electron microscopy(SEM),fluid inclusion thermometry,and core analysis,the reservoir rock types,dominant diageneses,diagenetic history,and controls on high-graded reservoirs were investigated.It is found that the Xu4 Member in Jianyang mainly consists of lithic feldspar sandstones and feldspar lithic sandstones,followed by lithic quartz sandstones.High-energy hydrodynamic conditions in the microfacies of underwater distributary channels and mouth bars are beneficial to the preservation of primary pores and the occurrence of secondary pores,and there are no significant differences in petrophysical properties between these two microfacies.Compaction and calcareous cementation are the dominant controls on reservoir porosity decrease in the Xujiahe Formation;corrosion is the major contributor to porosity increase by generating secondary dissolved pores,e.g.intragranular dissolved pores and intergranular dissolved pores,as major reservoir space in the study area.Fracture zones around the faults inside the Xujiahe Formation(fourth‒order faults)are favorable for proximal tight gas accumulation,preservation,and production.The research findings have been successfully applied to explore the Xujiahe Formation in the slope zone of the Sichuan foreland basin.They can be referential for other similar tight sandstone gas accumulations.
基金supported by National Natural Science Foundation of China(No.82372888)National Key Research and Development Program of China(No.2022YFC2704000)+6 种基金National Natural Science Foundation of China(No.82273383)the Capital’s Funds for Health Improvement and Research(No.2020-2-4098)Youth program of Beijing Municipal Natural Science Foundation(No.7204328)Clinical Medicine Plus X-Young Scholars Project,Peking University(No.PKU2022LCXQ020)Key Clinical Project of Peking University Third Hospital(No.BYSY2022050)Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2021006)Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2019034).
文摘Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the prognosis of patients with advanced high-grade serous ovarian cancer(HGSOC)remain unclear.Methods:We assessed the percentages of PD-1^(+)and CD57^(+)CD8^(+)T cells in tumor-infiltrating lymphocytes(TILs,n=85)and tumor ascites lymphocytes(TALs,n=87)using flow cytometry.The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method.Gene expression analysis elucidated the tumor immune microenvironment(TIME,n=36).Results:Patients with higher PD-1^(+)CD8^(+)TILs(>87.8%)exhibited longer platinum-free interval(PFI)and overall survival(OS).In contrast,those with elevated CD57^(+)CD8^(+)TALs(>28.69%)were more likely to experience chemotherapy and had lower complete remission rates,shorter PFI and OS.PD-1^(+)CD8^(+)TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities.Approximately 50%of CD57^(+)CD8^(+)TALs were terminally differentiated,exhibiting significantly impaired proliferation.Based on the proportions of PD-1^(+)CD8^(+)TILs and CD57^(+)CD8^(+)TALs,patients were categorized into good,median and poor prognosis groups,with median PFI of 47.78,27.29 and 11.96 months,respectively(P<0.0001).Median OS for these groups was not reach,49.23 and 30.92 months,respectively(P<0.0001).Patients with poor prognosis exhibit significantly reduced CD8^(+)T cell proportion and increased M2 macrophage in the TIME,alongside downregulation of multiple T cell activation-related pathways.Conclusions:Lower levels of PD-1^(+)CD8^(+)TILs and higher CD57^(+)CD8^(+)TALs,assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.
