Objective:To investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.

Objective:The association between air pollutants and the risk of sudden cardiac death (SCD) remains controversial. This study aimed to investigate the relationship between five air pollutants—PM 2.5, PM 2.5–10, PM 10, NO 2, and NO?—and the risk of SCD. Methods:We analyzed data from 460 862 participants in the UK Biobank cohort, all enrolled between 2006 and 2010, with no baseline SCD. Follow-up continued until the study endpoint. Annual average concentrations of the five pollutants were assessed. Associations between pollutants and SCD were evaluated using Cox proportional hazards models, followed by Mendelian randomization (MR) to assess causality.Results:Over a mean follow-up of 12.4 years, 2 662 SCD cases were recorded. After adjusting for confounders, no significant associations were found between air pollutants and SCD risk: PM 2.5 ( HR 1.03, 95% CI 0.99–1.07, P = 0.14), PM 2.5–10 ( HR 1.04, 95% CI 1.00–1.08, P = 0.08), PM 10 ( HR 1.01, 95% CI 0.99–1.03, P = 0.26), NO? ( HR 1.00, 95% CI 0.99–1.00, P = 0.26), and NO x ( HR 1.00, 95% CI 1.00–1.01, P = 0.19). MR analysis further supported the absence of causal relationships: PM 2.5 ( β = -0.149, P = 0.90), PM 2.5–10 ( β = 0.387, P = 0.62), PM 10 ( β = -0.994, P = 0.62), NO? ( β = –0.005, P = 0.99), and NO 2 ( β = –0.827, P = 0.25). Conclusions:This study found no evidence linking PM 2.5, PM 2.5–10, PM 10, NO?, or NO 2 to an increased risk of SCD. Mendelian randomization confirmed the lack of causal associations between these pollutants and SCD.

Objective:To investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated. Here, using conditional-knockout mice, we found that astrocytic HMGB1 depletion decreased morbidity, delayed the onset time, and reduced the disease score and demyelination of EAE. Meanwhile, there were fewer immune cells, especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice, accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo. In vitro, HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells (BMECs) through TLR4 or RAGE. Taken together, our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; HMGB1 Protein/metabolism* ; Endothelial Cells/metabolism* ; Mice, Inbred C57BL ; Mice, Knockout ; Blood-Brain Barrier/metabolism*

AIM:To observe the expression of hypoxia-inducible factor 1 (HIF-1) and neuroglobin (NGB) in piglet cortex during deep hypothermic circulatory arrest.METHODS:Wuzhishan piglets were randomly assigned to car-diopulmonary bypass group ( CPB group) , 40 min of circulatory arrest ( CA) at 18 ℃ without cerebral perfusion ( DHCA group) or with selective antegrade cerebral perfusion ( SACP group) .After 180 min of reperfusion, cortical tissue was har-vested for determining HIF-1αand NGB expression by HE staining, Western blot and real-time PCR.RESULTS:Severer cerebral injury was observed in DHCA group than that in SACP group.After 180 min of reperfusion, HIF-1αprotein and mRNA levels were significantly higher in DHCA group than those in CPB group (P<0.05).Accordingly, SACP animal had higher levels of HIF-1αprotein and mRNA than those in DHCA group (P<0.05).Simultaneously, higher NGB pro-tein and mRNA levels were found in DHCA group than those in CPB group after 180 min of reperfusion ( P<0.05) .The SACP animal had higher levels of NGB protein and mRNA than those in DHCA group (P<0.05).CONCLUSION:Up-regulation of HIF-1 and NGB are involved in the mechanism against cerebral injury resulting from DHCA in the cortex and possibly a part of cerebral protective effect of SACP.