The Zaire Ebola virus(EBOV)and Bundibugyo virus(BDBV)cause severe hemorrhagic fever with high mortality,highlighting the urgent need for broad-spectrum antiviral therapies.Neutralizing nanobodies,with their small size...The Zaire Ebola virus(EBOV)and Bundibugyo virus(BDBV)cause severe hemorrhagic fever with high mortality,highlighting the urgent need for broad-spectrum antiviral therapies.Neutralizing nanobodies,with their small size,structural stability,and ability to access sterically restricted epitopes,represent a promising antiviral modality.Here,we identified a high-affinity nanobody,BDBV-Nb02,from a fully synthetic phage display library targeting the glycan cap of BDBV glycoprotein(GP1).BDBV-Nb02 demonstrated strong binding kinetics(KD≈1 nM)and potent neutralizing activity against both BDBV and EBOV pseudoviruses,with half-maximal inhibitory concentration(IC50)values in the nanomolar range.Engineering a bivalent format significantly enhanced neutralization potency,achieving up to a 56-fold reduction in the 90%inhibitory concentration(IC90)compared with the monovalent form.Epitope competition assays and molecular docking revealed that BDBV-Nb02 targets a conserved glycan cleft,with residues F248 and NP278/279 identified as critical neutralization sites.In contrast,Fc-fusion constructs impaired the nanobody's efficacy,highlighting the importance of preserving the structural features that enable access to glycan-shielded epitopes.Our findings demonstrate that BDBV-Nb02 is a promising candidate for broad-spectrum orthoebolavirus therapy and may serve as a valuable component in future antiviral cocktail formulations.展开更多
To investigate the bearing behavior and failure modes of six-pile thick pile caps under different reinforcement configurations and explore the optimal reinforcement scheme,this study examined four scaled specimens(S1-...To investigate the bearing behavior and failure modes of six-pile thick pile caps under different reinforcement configurations and explore the optimal reinforcement scheme,this study examined four scaled specimens(S1-S4)with distinct reinforcement designs.The bearing capacity of each pile cap was first calculated using various methods,and laboratory tests were then conducted to determine cracking and ultimate loads.Reinforcement stresses and key strain measurements in the pile caps were monitored,and the crack propagation process was documented in detail.The results demonstrate that the spatial truss model yielded calculations closest to experimental values.Specimen S3 with mesh reinforcement exhibited the highest bearing capacity but required greater steel consumption.The truss-reinforced S4 showed enhanced ductility at failure but posed constructability challenges.Uniformly reinforced S1 delivered the lowest bearing capacity and developed more uneven cracks.Furthermore,a comprehensive analysis of reinforcement stress distribution,internal force flow transfer,and the validity of the plane-section assumption at the pile-cap sides revealed that the mechanical behavior of the six-pile thick pile cap is more closely aligned with the spatial truss model.The concentrated reinforcement scheme at the pile head,as suggested by this model,proves to be an efficient and practical design solution.展开更多
BACKGROUND Non-variceal upper gastrointestinal bleeding(NVUGIB)remains a common and potentially life-threatening emergency despite advances in endoscopic therapy.Endoscopic transparent caps(CAPs)have been proposed to ...BACKGROUND Non-variceal upper gastrointestinal bleeding(NVUGIB)remains a common and potentially life-threatening emergency despite advances in endoscopic therapy.Endoscopic transparent caps(CAPs)have been proposed to enhance lesion visualization and procedural stability,but their effect on clinical outcomes is uncertain.AIM To evaluate whether CAP use during therapeutic endoscopy influences hemostatic efficacy and short-term outcomes in NVUGIB.METHODS A total of 206 patients who underwent emergency endoscopic hemostasis between 2021 and 2025 at six tertiary centers in Türkiye were included.Patients were divided into CAP-assisted(n=67)and non-CAP(n=139)groups.Baseline characteristics,comorbidities,Glasgow-Blatchford and Rockall scores,hemostatic methods,and clinical outcomes were analyzed.Multivariable linear regression identified independent predictors of post-admission transfusion requirement and hospital length of stay(LOS).RESULTS Baseline demographic and clinical variables were comparable between groups.CAP was more often used in hemodynamically unstable patients.The CAP group required a greater number of hemostatic techniques(2.66±1.00 vs 2.14±0.87;P<0.001),with higher use of Ankaferd Blood Stopper and argon plasma coagulation,but received fewer post-admission transfusions(14.8%vs 33.8%;P=0.006)and a lower transfusion volume(0.44±1.13 U vs 0.91±1.31 U;P=0.012).Mortality,intensive-care need,and LOS did not differ significantly.CAP use independently predicted reduced transfusion volume(β=-0.47,P=0.010),whereas higher Charlson Comorbidity index and intensive care unit admission predicted longer LOS.CONCLUSION CAP-assisted endoscopy may improve procedural efficiency and hemostatic control in NVUGIB,reducing transfusion requirements without affecting mortality or hospitalization.Prospective randomized trials are warranted to validate these findings and clarify CAP’s role in standardized bleeding management.展开更多
BACKGROUND Cap polyposis(CP)is a rare benign colorectal disorder characterized by polyps capped with fibrinopurulent exudate and is frequently misdiagnosed as inflammatory bowel disease because of overlapping clinical...BACKGROUND Cap polyposis(CP)is a rare benign colorectal disorder characterized by polyps capped with fibrinopurulent exudate and is frequently misdiagnosed as inflammatory bowel disease because of overlapping clinical and histological features.No consensus exists regarding optimal management strategies.The aim of this study was to establish a standardized stepwise management algorithm for CP based on lesion distribution,number,size,and symptom severity,with the hypothesis that such an approach will optimize therapeutic outcomes while minimizing unnecessary interventions.AIM To clarify the clinical features,endoscopic findings,treatments and short-term outcomes of colorectal CP and provide clinical information for the diagnosis and treatment of this rare disease.METHODS We retrospectively collected data from seven consecutive patients with histologically confirmed CP who were treated at our center between January 2022 and January 2025.RESULTS The cohort comprised six males and one female(median age 36 years).Hematochezia was the main symptom(n=3),and two patients had hypoalbuminemia.Five patients had solitary lesions and two patients had multiple lesions.All the polyps had a characteristic“cap-like”appearance with white fibrinous exudate covering the surface.Histology revealed elongated,dilated crypts and mucosal hyperplasia covered by granulation tissue.One patient with small,asymptomatic lesions was kept under surveillance.Three patients underwent endoscopic mucosal resection,and three underwent transanal excision.Symptoms resolved in all treated patients.During a median follow-up of 18 months(range 10-30 m),no recurrence was detected.CONCLUSION In this small series,CP affected mainly males and resulted in rectal bleeding.Both endoscopic and transanal resection relieved symptoms,but larger studies with longer follow-up periods are needed to confirm long-term efficacy.展开更多
BACKGROUND Persistent microbial contamination of duodenoscopes remains a critical vector for healthcare-associated infections involving multidrug-resistant organisms.Despite adherence to standard high-level disinfecti...BACKGROUND Persistent microbial contamination of duodenoscopes remains a critical vector for healthcare-associated infections involving multidrug-resistant organisms.Despite adherence to standard high-level disinfection(HLD)protocols,contamination rates remain alarming.To mitigate this risk,the United States Food and Drug Administration has recommended transitioning to duodenoscopes with disposable components.AIM To investigate the efficacy of disposable distal cap compared to standard duodenoscope reprocessing with HLD in reducing microbial contamination.METHODS Following Preferred Reporting Items for Systematic Reviews and Meta-analysis and Cochrane guidelines,we conducted a systematic search of MEDLINE,EMBASE,Google Scholar,and grey literature for randomized controlled trials comparing disposable distal cap vs standard duodenoscopes.The primary outcome was the rate of microbial contamination,defined as an adenosine triphosphate level>40 relative light unit.Risk ratio was pooled using a random-effects model,and the quality of evidence was assessed using the Grading Recommendations Assessment,Development,and Evaluation methodology.RESULTS Four randomized controlled trials met the inclusion criteria,encompassing 1092 duodenoscopes(543 disposable distal cap,549 standard).The use of disposable cap demonstrated a significant and substantial reduction in post-HLD contamination rates.The pooled analysis showed a risk ratio of 0.32(95%confidence interval:0.16-0.67;P=0.003),representing a 68%reduction in contamination risk.No statistical heterogeneity was detected(I2=0%).The overall quality of evidence for this outcome was rated as high.CONCLUSION Disposable distal cap significantly decreases microbial contamination rates compared to standard duodenoscope reprocessing protocols.This technology represents a robust and effective strategy to enhance the safety of duodenoscope reprocessing.展开更多
Ming-style furniture represents the pinnacle of Chinese traditional furniture,with the four-head official’s cap chair standing out as a representative category due to its classic form and cultural connotations.This p...Ming-style furniture represents the pinnacle of Chinese traditional furniture,with the four-head official’s cap chair standing out as a representative category due to its classic form and cultural connotations.This paper takes a specific rosewood four-head official’s cap chair inscribed by Wang Shixiang as the research subject,employing a tripartite approach of form analysis,material examination,and inscription interpretation.The chair strictly adheres to the classic form of Ming-style four-head official’s cap chairs,embodying the Ming Dynasty design philosophy of“the unity of function and aesthetics”.The scarcity and unique grain pattern of the golden-flecked rosewood(Zitan)endow it with the status of“gold among woods”.Wang Shixiang’s inscription binds the furniture to the cultural essence of“the charm of the Ming Dynasty”,transforming it into“heritable cultural heritage”.This paper provides a new perspective for the case study of Ming-style furniture and offers theoretical reference for the contemporary inheritance of traditional craftsmanship.展开更多
On the vast land of Xigaze,more than 4,000 meters above sea level,snow-capped mountains stretch endlessly.The wind sweeps across the land,carrying the sweet fragrance of highland barley and stirring the rhythmic sound...On the vast land of Xigaze,more than 4,000 meters above sea level,snow-capped mountains stretch endlessly.The wind sweeps across the land,carrying the sweet fragrance of highland barley and stirring the rhythmic sound of reading that rises and falls across the campus.From kindergarten to high school,education is a bridge that lifts the gaze of children on the plateau,carrying it over the snow-capped mountains toward a vaster horizon.展开更多
基金supported by grants from the National Natural Science Foundation of China(U22A20553 and 82241064)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2025-I2M-KJ-022 and 2021-I2M-1-038)the Fundamental Research Funds for the Central Universities of Peking Union Medical College(3332024204).
摘要The Zaire Ebola virus(EBOV)and Bundibugyo virus(BDBV)cause severe hemorrhagic fever with high mortality,highlighting the urgent need for broad-spectrum antiviral therapies.Neutralizing nanobodies,with their small size,structural stability,and ability to access sterically restricted epitopes,represent a promising antiviral modality.Here,we identified a high-affinity nanobody,BDBV-Nb02,from a fully synthetic phage display library targeting the glycan cap of BDBV glycoprotein(GP1).BDBV-Nb02 demonstrated strong binding kinetics(KD≈1 nM)and potent neutralizing activity against both BDBV and EBOV pseudoviruses,with half-maximal inhibitory concentration(IC50)values in the nanomolar range.Engineering a bivalent format significantly enhanced neutralization potency,achieving up to a 56-fold reduction in the 90%inhibitory concentration(IC90)compared with the monovalent form.Epitope competition assays and molecular docking revealed that BDBV-Nb02 targets a conserved glycan cleft,with residues F248 and NP278/279 identified as critical neutralization sites.In contrast,Fc-fusion constructs impaired the nanobody's efficacy,highlighting the importance of preserving the structural features that enable access to glycan-shielded epitopes.Our findings demonstrate that BDBV-Nb02 is a promising candidate for broad-spectrum orthoebolavirus therapy and may serve as a valuable component in future antiviral cocktail formulations.
基金The National Natural Science Foundation of China(No.52378328,52208333,52178317)Research Fund for AdvancedOcean Institute of Southeast University(No.KP202404,GP202403).
摘要To investigate the bearing behavior and failure modes of six-pile thick pile caps under different reinforcement configurations and explore the optimal reinforcement scheme,this study examined four scaled specimens(S1-S4)with distinct reinforcement designs.The bearing capacity of each pile cap was first calculated using various methods,and laboratory tests were then conducted to determine cracking and ultimate loads.Reinforcement stresses and key strain measurements in the pile caps were monitored,and the crack propagation process was documented in detail.The results demonstrate that the spatial truss model yielded calculations closest to experimental values.Specimen S3 with mesh reinforcement exhibited the highest bearing capacity but required greater steel consumption.The truss-reinforced S4 showed enhanced ductility at failure but posed constructability challenges.Uniformly reinforced S1 delivered the lowest bearing capacity and developed more uneven cracks.Furthermore,a comprehensive analysis of reinforcement stress distribution,internal force flow transfer,and the validity of the plane-section assumption at the pile-cap sides revealed that the mechanical behavior of the six-pile thick pile cap is more closely aligned with the spatial truss model.The concentrated reinforcement scheme at the pile head,as suggested by this model,proves to be an efficient and practical design solution.
摘要BACKGROUND Non-variceal upper gastrointestinal bleeding(NVUGIB)remains a common and potentially life-threatening emergency despite advances in endoscopic therapy.Endoscopic transparent caps(CAPs)have been proposed to enhance lesion visualization and procedural stability,but their effect on clinical outcomes is uncertain.AIM To evaluate whether CAP use during therapeutic endoscopy influences hemostatic efficacy and short-term outcomes in NVUGIB.METHODS A total of 206 patients who underwent emergency endoscopic hemostasis between 2021 and 2025 at six tertiary centers in Türkiye were included.Patients were divided into CAP-assisted(n=67)and non-CAP(n=139)groups.Baseline characteristics,comorbidities,Glasgow-Blatchford and Rockall scores,hemostatic methods,and clinical outcomes were analyzed.Multivariable linear regression identified independent predictors of post-admission transfusion requirement and hospital length of stay(LOS).RESULTS Baseline demographic and clinical variables were comparable between groups.CAP was more often used in hemodynamically unstable patients.The CAP group required a greater number of hemostatic techniques(2.66±1.00 vs 2.14±0.87;P<0.001),with higher use of Ankaferd Blood Stopper and argon plasma coagulation,but received fewer post-admission transfusions(14.8%vs 33.8%;P=0.006)and a lower transfusion volume(0.44±1.13 U vs 0.91±1.31 U;P=0.012).Mortality,intensive-care need,and LOS did not differ significantly.CAP use independently predicted reduced transfusion volume(β=-0.47,P=0.010),whereas higher Charlson Comorbidity index and intensive care unit admission predicted longer LOS.CONCLUSION CAP-assisted endoscopy may improve procedural efficiency and hemostatic control in NVUGIB,reducing transfusion requirements without affecting mortality or hospitalization.Prospective randomized trials are warranted to validate these findings and clarify CAP’s role in standardized bleeding management.
基金Supported by National Natural Science Foundation of China, No. 82373163.
摘要BACKGROUND Cap polyposis(CP)is a rare benign colorectal disorder characterized by polyps capped with fibrinopurulent exudate and is frequently misdiagnosed as inflammatory bowel disease because of overlapping clinical and histological features.No consensus exists regarding optimal management strategies.The aim of this study was to establish a standardized stepwise management algorithm for CP based on lesion distribution,number,size,and symptom severity,with the hypothesis that such an approach will optimize therapeutic outcomes while minimizing unnecessary interventions.AIM To clarify the clinical features,endoscopic findings,treatments and short-term outcomes of colorectal CP and provide clinical information for the diagnosis and treatment of this rare disease.METHODS We retrospectively collected data from seven consecutive patients with histologically confirmed CP who were treated at our center between January 2022 and January 2025.RESULTS The cohort comprised six males and one female(median age 36 years).Hematochezia was the main symptom(n=3),and two patients had hypoalbuminemia.Five patients had solitary lesions and two patients had multiple lesions.All the polyps had a characteristic“cap-like”appearance with white fibrinous exudate covering the surface.Histology revealed elongated,dilated crypts and mucosal hyperplasia covered by granulation tissue.One patient with small,asymptomatic lesions was kept under surveillance.Three patients underwent endoscopic mucosal resection,and three underwent transanal excision.Symptoms resolved in all treated patients.During a median follow-up of 18 months(range 10-30 m),no recurrence was detected.CONCLUSION In this small series,CP affected mainly males and resulted in rectal bleeding.Both endoscopic and transanal resection relieved symptoms,but larger studies with longer follow-up periods are needed to confirm long-term efficacy.
摘要BACKGROUND Persistent microbial contamination of duodenoscopes remains a critical vector for healthcare-associated infections involving multidrug-resistant organisms.Despite adherence to standard high-level disinfection(HLD)protocols,contamination rates remain alarming.To mitigate this risk,the United States Food and Drug Administration has recommended transitioning to duodenoscopes with disposable components.AIM To investigate the efficacy of disposable distal cap compared to standard duodenoscope reprocessing with HLD in reducing microbial contamination.METHODS Following Preferred Reporting Items for Systematic Reviews and Meta-analysis and Cochrane guidelines,we conducted a systematic search of MEDLINE,EMBASE,Google Scholar,and grey literature for randomized controlled trials comparing disposable distal cap vs standard duodenoscopes.The primary outcome was the rate of microbial contamination,defined as an adenosine triphosphate level>40 relative light unit.Risk ratio was pooled using a random-effects model,and the quality of evidence was assessed using the Grading Recommendations Assessment,Development,and Evaluation methodology.RESULTS Four randomized controlled trials met the inclusion criteria,encompassing 1092 duodenoscopes(543 disposable distal cap,549 standard).The use of disposable cap demonstrated a significant and substantial reduction in post-HLD contamination rates.The pooled analysis showed a risk ratio of 0.32(95%confidence interval:0.16-0.67;P=0.003),representing a 68%reduction in contamination risk.No statistical heterogeneity was detected(I2=0%).The overall quality of evidence for this outcome was rated as high.CONCLUSION Disposable distal cap significantly decreases microbial contamination rates compared to standard duodenoscope reprocessing protocols.This technology represents a robust and effective strategy to enhance the safety of duodenoscope reprocessing.
摘要Ming-style furniture represents the pinnacle of Chinese traditional furniture,with the four-head official’s cap chair standing out as a representative category due to its classic form and cultural connotations.This paper takes a specific rosewood four-head official’s cap chair inscribed by Wang Shixiang as the research subject,employing a tripartite approach of form analysis,material examination,and inscription interpretation.The chair strictly adheres to the classic form of Ming-style four-head official’s cap chairs,embodying the Ming Dynasty design philosophy of“the unity of function and aesthetics”.The scarcity and unique grain pattern of the golden-flecked rosewood(Zitan)endow it with the status of“gold among woods”.Wang Shixiang’s inscription binds the furniture to the cultural essence of“the charm of the Ming Dynasty”,transforming it into“heritable cultural heritage”.This paper provides a new perspective for the case study of Ming-style furniture and offers theoretical reference for the contemporary inheritance of traditional craftsmanship.
摘要On the vast land of Xigaze,more than 4,000 meters above sea level,snow-capped mountains stretch endlessly.The wind sweeps across the land,carrying the sweet fragrance of highland barley and stirring the rhythmic sound of reading that rises and falls across the campus.From kindergarten to high school,education is a bridge that lifts the gaze of children on the plateau,carrying it over the snow-capped mountains toward a vaster horizon.