BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
The aim of this paper was to identify the trends and hot topics in the study of scientific collaboration via scientometric analysis. Information visualization and knowledge domain visualization techniques were adopted...The aim of this paper was to identify the trends and hot topics in the study of scientific collaboration via scientometric analysis. Information visualization and knowledge domain visualization techniques were adopted to determine how the study of scientific collaboration has evolved. A total of 1,455 articles on scientific cooperation published between 1993 and 2007 were retrieved from the SCI, SSCI and A&HCI databases with a topic search of scientific collaboration or scientific cooperation for the analysis. By using CiteSpace, the knowledge bases, research foci, and research fronts in the field of scientific collaboration were studied. The results indicated that research fronts and research foci are highly consistent in terms of the concept, origin, measurement, and theory of scientific collaboration. It also revealed that research fronts included scientific collaboration networks, international scientific collaboration, social network analysis and techniques, and applications of bibliometrical indicators, webmetrics, and health care related areas.展开更多
Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin recept...Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.展开更多
BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and li...BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-ric...BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-rich plasma(PRP)is a concentrated platelet product that can trigger the release of growth factors and cytokines,which stimulate tissue healing and regeneration and thus alleviates DFU.At present,no comprehensive study has been conducted to verify the effect of PRP in both in vitro and clinical settings for treating DFUs.AIM To perform the in vitro and clinical evaluation of PRP combined with endovascular angioplasty in treating diabetic foot.METHODS This study focused on both in vitro and clinical settings.In the in vitro study,human umbilical vein endothelial cells(HUVECs),human dermal fibroblasts(HSFs),and human immortalized keratinocytes(HaCaTs)were treated with PRP.Experiments involving proliferation,migration,tubule formation,and angiogenesis signaling pathways were conducted.In this clinical study,patients who visited the Affiliated Panyu Central Hospital of Guangzhou Medical University from 2020 to 2024 and met enrollment criteria were randomly assigned to 2 groups using prospective block randomization.In the control group,the DFU was treated with endovascular angioplasty and wound debridement.In the PRP+endovascular angioplasty group,PRP was evenly used on the surface of superficial ulcers,followed by endovascular angioplasty to treat vascular occlusion.The key outcomes were measured,including the Rutherford scale,Wagner scale,foot skin temperature,and ulcer repair area before and after treatment.RESULTS In the in vitro study,6%PRP could promote the proliferation and migration of HUVECs,HSFs,and HaCaTs in a high-glucose environment.Additionally,it promoted tubule formation in HUVECs by activating signaling proteins such as Ak strain transforming and extracellular regulated protein kinases 1/2.In the clinical study,a total of 208 patients participated.After 12 months of treatment,the ulcer repair area(14.95±0.16 cm^(2))and ulcer healing rate were improved in the PRP+endovascular angioplasty group than in the control group(P<0.05).CONCLUSION The combination of 6%activated PRP and endovascular angioplasty may improve the microcirculation and tissue repair in DFUs.This study offers a novel treatment option for patients with diabetic foot.展开更多
Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain la...Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.展开更多
Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the...Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.展开更多
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
基金supported by the National Natural Science Foundation of China(Grant Nos.70773015,70431001 and 70620140115)the National Social Sciences Foundation(Grant No.07CTQ008)the Project of DUT(Grant No.DUTHS1002)
文摘The aim of this paper was to identify the trends and hot topics in the study of scientific collaboration via scientometric analysis. Information visualization and knowledge domain visualization techniques were adopted to determine how the study of scientific collaboration has evolved. A total of 1,455 articles on scientific cooperation published between 1993 and 2007 were retrieved from the SCI, SSCI and A&HCI databases with a topic search of scientific collaboration or scientific cooperation for the analysis. By using CiteSpace, the knowledge bases, research foci, and research fronts in the field of scientific collaboration were studied. The results indicated that research fronts and research foci are highly consistent in terms of the concept, origin, measurement, and theory of scientific collaboration. It also revealed that research fronts included scientific collaboration networks, international scientific collaboration, social network analysis and techniques, and applications of bibliometrical indicators, webmetrics, and health care related areas.
文摘Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.
基金Supported by Special Research Plan 2023 of Chaozhou,No.202303GY05。
文摘BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.
基金Supported by the Medical Science and Technology Foundation of Guangdong Province,No.A2024625the Guangzhou Municipal Science and Technology Program Key Projects,No.202103000002the Panyu Science and Technology Planning Project,No.2023-Z04-019.
文摘BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-rich plasma(PRP)is a concentrated platelet product that can trigger the release of growth factors and cytokines,which stimulate tissue healing and regeneration and thus alleviates DFU.At present,no comprehensive study has been conducted to verify the effect of PRP in both in vitro and clinical settings for treating DFUs.AIM To perform the in vitro and clinical evaluation of PRP combined with endovascular angioplasty in treating diabetic foot.METHODS This study focused on both in vitro and clinical settings.In the in vitro study,human umbilical vein endothelial cells(HUVECs),human dermal fibroblasts(HSFs),and human immortalized keratinocytes(HaCaTs)were treated with PRP.Experiments involving proliferation,migration,tubule formation,and angiogenesis signaling pathways were conducted.In this clinical study,patients who visited the Affiliated Panyu Central Hospital of Guangzhou Medical University from 2020 to 2024 and met enrollment criteria were randomly assigned to 2 groups using prospective block randomization.In the control group,the DFU was treated with endovascular angioplasty and wound debridement.In the PRP+endovascular angioplasty group,PRP was evenly used on the surface of superficial ulcers,followed by endovascular angioplasty to treat vascular occlusion.The key outcomes were measured,including the Rutherford scale,Wagner scale,foot skin temperature,and ulcer repair area before and after treatment.RESULTS In the in vitro study,6%PRP could promote the proliferation and migration of HUVECs,HSFs,and HaCaTs in a high-glucose environment.Additionally,it promoted tubule formation in HUVECs by activating signaling proteins such as Ak strain transforming and extracellular regulated protein kinases 1/2.In the clinical study,a total of 208 patients participated.After 12 months of treatment,the ulcer repair area(14.95±0.16 cm^(2))and ulcer healing rate were improved in the PRP+endovascular angioplasty group than in the control group(P<0.05).CONCLUSION The combination of 6%activated PRP and endovascular angioplasty may improve the microcirculation and tissue repair in DFUs.This study offers a novel treatment option for patients with diabetic foot.
基金supported by the National Natural Science Foundation of China(31600139)the Chongqing Science and Technology Bureau(cstc2016jcyjA0020+3 种基金CSTB2024NSCQ-KJFZMSX0067)the Yuzhong District Science and Technology Commission(20190123)the Chongqing Municipal Education Commission(KJQN202300415)the Project of Undergraduates Innovating Experiment,and the Project of Tutorial System of Excellent Medical Undergraduates in the Lab Teaching and Management Center of Chongqing Medical University(S202410631068,LTMCMTS202458,LTMCMTS202459,LTMCMTS202460 and LTMCMTS202461).
文摘Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.
基金supported by the STI2030-Major Projects(2021ZD0204001)the National Natural Science Foundation of China(92049120,81870897,81271424,81671111,and 62475179)+8 种基金the Sino German Cooperation and Exchange Project(M-0679)the Guangdong Key Project in the Development of New Tools for the Diagnosis and Treatment of Autism(2018B030335001)the Natural Science Foundation of Jiangsu Province(BK20181436)the Priority Academic Program Development of Jiangsu Higher Education Institutions,the Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases(BM2013003)Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,Suzhou Science and Technology Plan Medical and Health Care Science and Technology Innovation Applied Basic Research(SKY2022161)the Research Project of Neurological Diseases in the Second Affiliated Hospital of Soochow University Research Center(ND2023A01)Boxi clinical research project of The First Affiliated Hospital of Soochow University(BXQN202204)Suzhou Science&Technology Projects for People's Livelihood(SKY2021065)Wuxi Municipal Health Commission(M202204).
文摘Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
