Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke. The evaluation of its structure and function is of great significance for formulating clinical intervention strategies. The indications for endovascular treatment of ICAS lesions in the past were mainly based on the degree of luminal stenosis showed by cerebral angiography, which had certain limitations. The translesional pressure ratio (PR), as an important indicator for functional assessment after arterial stenosis, has gradually received attention in the evaluation of ICAS lesions in recent years. This article reviews the evaluation methods and clinical significance of PR in ICAS lesions.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective:To compare the protective effects of the static cold storage (SCS) and normothermic machine perfusion (NMP) on the skeletal muscle of the amputated limbs of pigs.Methods:Four Landrace pigs were selected, from which eight limbs were amputated and divided into SCS group ( n=5) and NMP group ( n=3) according to the random number table method. After blood collection from the carotid artery, an amputated limb model was established by amputating the limbs at the scapulohumeral joints. The limbs in the SCS group were wrapped in sterile cloth and stored at 4 ℃ for 24 hours. In the NMP group, the limbs were mechanically perfused with a red blood cell-containing perfusion fluid at 37 ℃ for 24 hours, with 70% of the perfusion fluid replaced every 6 hours. Before the experiment, cross-matching tests with the saline medium were conducted between donor and recipient pigs to evaluate blood coagulation and blood safety in the NMP group. An allogeneic red blood cell perfusion fluid was prepared and the levels of pH, Na +, K +, Cl -, Ca 2+, glucose (Glu), hematocrit (Hct), lactic acid (Lac) and osmotic pressure of the perfusion fluid were measured. At 0, 6, 12, 18, and 24 hours after perfusion, the skin temperature and oxyhemoglobin saturation (SaO 2) levels in the NMP group were monitored and the levels of pH, Glu, creatine kinase (Ck), K +, Ca 2+, and Na +levels of the perfusion fluid were analyzed to evaluate the metabolism of the skeletal muscle in the amputated limbs. The mean intercellular distance and apoptosis index of the myocytes were quantitatively analyzed and histopathological changes were observed by performing HE staining and TUNEL staining on the skeletal muscle of the amputated limbs in both groups at 0 and 24 hours after perfusion. After perfusion was ended, the weight gain rate and swelling degree of the amputated limbs were compared between the two groups and the overall state of the amputated limbs was evaluated. Results:The result of the cross-matching test between donor and recipient pig blood was negative. The parameters in the prepared red blood cell-containing perfusion fluid generally maintained within a normal range: pH 7.38±0.04, Na + concentration (138.30±4.48)mmol/L, K + concentration (3.50±0.26)mmol/L, Glu concentration (6.11±2.08)mmol/L, and osmotic pressure (305.67±3.79)mmol/L. However, slightly higher Cl - and Ca 2+ concentrations [(118.34±12.00)mmol/L and (2.00±0.15)mmol/L] and lower Hct and lactate concentrations [0.30±0.03 and (1.54±0.38)mmol/L] were detected when compared with the reference range. During the perfusion, the average skin temperature of the amputated limbs in the NMP group was (36.13±0.98)℃, with the skin temperatures at 6, 12, 18, and 24 hours after perfusion being significantly higher than that at 0 hour ( P<0.01), while no significant difference among the skin temperatures at 6, 12, 18, and 24 hours after perfusion was observed ( P>0.05). The SaO 2 levels in the skin of the amputated limbs in the NMP group averaged over 95%, which showed no significant difference at 0, 12, 18, and 24 hours after perfusion ( P>0.05), while a significant elevation was observed at 6 hours compared with that at 0 hour ( P<0.05). There were no significant differences in pH, Glu, Na +, and Ca 2+ levels in the NMP group at 0, 6, 12, 18, and 24 hours after perfusion ( P>0.05), while the Ck levels at 18 and 24 hours were both significantly higher than that at 6 hours after perfusion ( P<0.05), and the Ck levels at 6, 12, 18, and 24 hours were all significantly higher than that at 0 hour ( P<0.05). The K + level progressively increased with the perfusion time, with significant elevations at 18 and 24 hours after perfusion compared with that at 0 hour ( P<0.05). HE staining revealed well-preserved muscle fiber continuity and regular arrangement in the NMP group and the SCS group at 0 hour, with an intercellular distance of (8.95±0.60)μm. At 24 hours, the NMP group exhibited slight skeletal muscle fiber rupture and swelling, with a slightly increased intercellular distance of (14.75±0.90)μm, significantly greater than that at 0 hour ( P<0.01). At 24 hours, the SCS group showed marked skeletal muscle fiber rupture and swelling, with a significantly increased intercellular distance of (23.51±1.49)μm, significantly larger than those at 0 hour in the same group and at 24 hours in the NMP group ( P<0.01). TUNEL immunofluorescence staining indicated a tiny amount of apoptotic cells in the skeletal muscle in both groups at 0 hour, with an apoptotic index of (4.26±1.62)%. There was a small number of apoptotic cells in the skeletal muscle in the NMP group at 24 hours, with an apoptotic index of (25.94±2.69)%, significantly larger than that in the same group at 0 hour ( P<0.01). The SCS group exhibited a large number of apoptotic cells at 24 hours, with an apoptotic index of (62.97±3.22)%, significantly larger than those at 0 hour in the same group and at 24 hours in the NMP group ( P<0.01). In comparison with the SCS group at 24 hours, the amputated limbs in the NMP group showed red color in the appearance, no symptoms of ischemic muscle contracture and good joint movement despite slight edema in the subcutaneous layer. At 24 hours, the weight gain rate of the amputated limbs was (15.82±0.89)% in the NMP group, significantly higher than (0.97±0.28)% in the SCS group ( P<0.01). Conclusion:Compared with SCS, NMP with the red blood cell-containing perfusion fluid prepared with the allogeneic blood for the amputated limbs of pigs can alleviate the ischemic injury of the muscle fibers and inhibit the apoptosis of the muscle cells by sustaining stable energy and oxygen supply and balancing ion homeostasis and pH of the perfusion fluid.

Although tumor immunotherapy has transformed cancer treatment，its efficacy against solid tumors remains limited by the immunosuppressive tumor microenvironment，inefficient drug delivery，and off-target toxicity. Engineered bacterial therapy has recently attracted considerable interest as a promising therapeutic strategy owing to its capacity for selective tumor colonization and immunomodulation. Meanwhile，ultrasound technology provides a non-invasive，spatially precise，and real-time controllable means to improve the performance and applicability of bacterial-mediated therapies. This review summarizes recent advances in ultrasound-regulated bacterial therapy for cancer immunotherapy. Beginning with an examination of the mechanisms through which engineered bacteria modulate antitumor immunity，it is followed by an elucidation of how ultrasound technology exploits its biological effects and spatiotemporal control capabilities to simultaneously enhance bacterial therapy's safety/efficacy and enable tumor treatment visualization，thereby activating systemic immune responses. Finally，current challenges and future directions for clinical translation are critically discussed. In conclusion，ultrasound-regulated bacterial therapy represents an emerging interdisciplinary approach with the potential to overcome key limitations in solid tumor immunotherapy.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.

OBJECTIVE To explore the epidemiological characteristics of common allergens among children with al-lergic rhinitis(AR)in a children's specialized hospital of Beijing.METHODS A total of 2120 children who met the diagnostic criteria of AR and were treated in otolaryngology department of Beijing Jingdu Children's Hospital from 2021 to 2023 were recruited as the research subjects.The specific immunoglobulin E(sIgE)of allergens was de-tected by western blot quantitative assay.The positive rates of the allergens were statistically analyzed according to the age,sex and years.The epidemiological characteristics and changing trends were observed.RESULTS The pos-itive rate of allergens was 47.78％among the 2120 children,in whom multiple allergies polysensitization were pre-dominant;the positive rate of allergens and polysensitization rate were the highest among the population aged be-tween 1 and 7 years old.The inhalational allergens were dominant,and the positive rate of the Candida group was highest.The positive rates of inhalant allergens and ingested allergens reached the peak at the age of 1-7 and then declined with age;milk and egg white were the two types of predominant ingested allergens in childhood.Among the 2120 children,there were significant differences in the positive rates of allergens between the male and the fe-male,and the positive rates of the male were higher than those of the female(P＜0.001).The positive rates of al-lergens generally showed upward trends during the 3 years,the positive rates of the inhalant allergens such as mugwort,cat hair and dog dandruff ascended by a large margin,and the positive rates of the ingested allergens such as milk,egg white and egg yolk showed remarkable rising trends.CONCLUSIONS The causes of AR are complicated.There are a variety of factors affecting the allergen test.The epidemiological characteristics of the al-lergens among the AR children are observed from multiple perspectives,which may provide references for preven-tion and treatment of the children with AR.

OBJECTIVE To explore the epidemiological characteristics of common allergens among children with al-lergic rhinitis(AR)in a children's specialized hospital of Beijing.METHODS A total of 2120 children who met the diagnostic criteria of AR and were treated in otolaryngology department of Beijing Jingdu Children's Hospital from 2021 to 2023 were recruited as the research subjects.The specific immunoglobulin E(sIgE)of allergens was de-tected by western blot quantitative assay.The positive rates of the allergens were statistically analyzed according to the age,sex and years.The epidemiological characteristics and changing trends were observed.RESULTS The pos-itive rate of allergens was 47.78％among the 2120 children,in whom multiple allergies polysensitization were pre-dominant;the positive rate of allergens and polysensitization rate were the highest among the population aged be-tween 1 and 7 years old.The inhalational allergens were dominant,and the positive rate of the Candida group was highest.The positive rates of inhalant allergens and ingested allergens reached the peak at the age of 1-7 and then declined with age;milk and egg white were the two types of predominant ingested allergens in childhood.Among the 2120 children,there were significant differences in the positive rates of allergens between the male and the fe-male,and the positive rates of the male were higher than those of the female(P＜0.001).The positive rates of al-lergens generally showed upward trends during the 3 years,the positive rates of the inhalant allergens such as mugwort,cat hair and dog dandruff ascended by a large margin,and the positive rates of the ingested allergens such as milk,egg white and egg yolk showed remarkable rising trends.CONCLUSIONS The causes of AR are complicated.There are a variety of factors affecting the allergen test.The epidemiological characteristics of the al-lergens among the AR children are observed from multiple perspectives,which may provide references for preven-tion and treatment of the children with AR.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Objective:To translate the Vascular Quality of Life Questionnaire-6 (VQ6) into a Chinese version and to test its reliability and validity in patients with peripheral arterial disease.Methods:The English version of VQ6 scale was sinicized following the Brislin translation guidelines, and the Delphi consultation was used for cultural debugging to form the Chinese version of the VQ6. Convenience sampling was used to select 146 patients with peripheral arterial disease who attended the Department of Interventional and Vascular Surgery and the Department of Endocrinology of Affiliated Hospital of Nantong University from May to June 2024 for the survey. Data were analyzed using SPSS 26.0 and Amos 26.0. Correlation analysis and critical ratio method were used for item analysis and content validity index was used to evaluate content validity. The Chinese version of the Patient-Reported Outcomes Measurement Information System 29 Profile V2.1 (PROMIS-29 Profile v2.1) was selected as a validity scale to evaluate the criterion-related validity. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the scale, and transgender test was used for measurement equivalence. Reliability of the scale was evaluated with the Cronbach's α coefficient and retest reliability index.Results:The Chinese version of the VQ6 scale had six items. The scale-level content validity index was 0.972, and the item-level content validity index ranged from 0.833 to 1.000. One common factor was extracted with a cumulative variance contribution of 83.526%. Criterion-related validity showed that the correlation coefficient between the Chinese version of the VQ6 and the PROMIS-29 Profile v2.1 was 0.688 ( P<0.01) . The scale essentially satisfied Δ RMSEA < 0.015 and Δ CFI < 0.01 in the transgender equivalence test. The Cronbach's α coefficient for the scale was 0.968 and the retest reliability was 0.978. Conclusions:The Chinese version of the VQ6 has good reliability and validity and is suitable as an assessment tool for quality of life in patients with peripheral arterial disease in our cultural context.