Objective:To investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

Objective:To evaluate the impact of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality and calculate the attributable mortality burden.Methods:This study collected road traffic mortality data from the Disease Surveillance System in Guangdong, Hunan, Zhejiang, Yunnan, and Jilin Provinces from 2013 to 2018. A time-stratified case-crossover design was used in this study, with the death date for each case serving as the case day. Control days were selected from the same year, month, and day of the week as the case day. A conditional logistic regression model was employed to estimate the cumulative associations of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality (lag 0-1 day) and to calculate the attributable fractions (AF).Results:Compared to non-heatwave days, the excess risk ( ER) of road traffic mortality on daytime heatwave days, nighttime heatwave days, and compound heatwave days was 5.3% (95% CI: 0.5%-10.2%), 4.9% (95% CI: 0.5%-9.4%) and 7.5% (95% CI: 2.3%- 12.9%), with corresponding AF of 5.0% (95% CI: 0.5%-9.3%), 4.7% (95% CI: 0.5%-8.6%), and 6.9% (95% CI: 2.3%-11.4%), respectively. Stratified analysis showed that the risk of traffic mortalities caused by daytime heatwaves was higher in females ( ER=15.7%, 95% CI: 5.8%-26.5%) than in males ( ER=1.8%, 95% CI: -3.6%-7.4%). Elderly individuals over 64 years old ( ER=10.9%, 95% CI: 0.3%- 22.6%) had a higher risk of road traffic mortalities from compound heatwaves than those under 45 years old ( ER=2.6%, 95% CI: -5.4%-11.2%). The risk of road traffic injury mortality from motor vehicle accidents caused by compound heatwaves ( ER=16.6%, 95% CI:2.4%-32.7%) was higher than that from non-motor vehicle accidents ( ER=5.7%, 95% CI:0.1%-11.5%). Conclusions:Short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves was associated with an increased risk of road traffic mortality, with the strongest association observed for compound heatwaves. The mortality burden attributable to compound heatwaves was higher than that for daytime and nighttime heatwaves. Heatwaves were more significantly associated with road traffic mortality risk among females, elderly individuals over 64 years old, and motor vehicle accidents.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.

Objective:To investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

Objective:To evaluate the impact of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality and calculate the attributable mortality burden.Methods:This study collected road traffic mortality data from the Disease Surveillance System in Guangdong, Hunan, Zhejiang, Yunnan, and Jilin Provinces from 2013 to 2018. A time-stratified case-crossover design was used in this study, with the death date for each case serving as the case day. Control days were selected from the same year, month, and day of the week as the case day. A conditional logistic regression model was employed to estimate the cumulative associations of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality (lag 0-1 day) and to calculate the attributable fractions (AF).Results:Compared to non-heatwave days, the excess risk ( ER) of road traffic mortality on daytime heatwave days, nighttime heatwave days, and compound heatwave days was 5.3% (95% CI: 0.5%-10.2%), 4.9% (95% CI: 0.5%-9.4%) and 7.5% (95% CI: 2.3%- 12.9%), with corresponding AF of 5.0% (95% CI: 0.5%-9.3%), 4.7% (95% CI: 0.5%-8.6%), and 6.9% (95% CI: 2.3%-11.4%), respectively. Stratified analysis showed that the risk of traffic mortalities caused by daytime heatwaves was higher in females ( ER=15.7%, 95% CI: 5.8%-26.5%) than in males ( ER=1.8%, 95% CI: -3.6%-7.4%). Elderly individuals over 64 years old ( ER=10.9%, 95% CI: 0.3%- 22.6%) had a higher risk of road traffic mortalities from compound heatwaves than those under 45 years old ( ER=2.6%, 95% CI: -5.4%-11.2%). The risk of road traffic injury mortality from motor vehicle accidents caused by compound heatwaves ( ER=16.6%, 95% CI:2.4%-32.7%) was higher than that from non-motor vehicle accidents ( ER=5.7%, 95% CI:0.1%-11.5%). Conclusions:Short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves was associated with an increased risk of road traffic mortality, with the strongest association observed for compound heatwaves. The mortality burden attributable to compound heatwaves was higher than that for daytime and nighttime heatwaves. Heatwaves were more significantly associated with road traffic mortality risk among females, elderly individuals over 64 years old, and motor vehicle accidents.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.