Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Objective:To analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Trench foot was first seen in World War Ⅰ and was one of the reasons for non combat attrition. We reviewed and analyzed 15 cases of trench foot admitted from 2010 to 2021, summarized clinical treatment methods and experiences, analyzed the causes, population characteristics, treatment methods, and treatment experiences of trench foot during peacetime, strengthened attention to high-risk groups, and improved the success rate of clinical treatment.

Trench foot was first seen in World War Ⅰ and was one of the reasons for non combat attrition. We reviewed and analyzed 15 cases of trench foot admitted from 2010 to 2021, summarized clinical treatment methods and experiences, analyzed the causes, population characteristics, treatment methods, and treatment experiences of trench foot during peacetime, strengthened attention to high-risk groups, and improved the success rate of clinical treatment.

Objective:To analyze the hemodynamic changes of different types of unruptured intracranial aneurysms before and after flow diverter (FD) treatment with computational fluid dynamics (CFD), and lay research foundation for precision treatment and prognosis evaluation for unruptured intracranial aneurysms.Methods:Four patients with different types of unruptured intracranial aneurysms, admitted to Department of Neurosurgery, First Affiliated Hospital of Air Force Medical University from January 2022 to March 2022, were chosen. Digital subtraction angiography (DSA) data of the patients before and immediately after surgery were collected. Morphological and hemodynamic parameters of the aneurysms were calculated by 3D reconstruction, finite element simulation, and CFD methods: ostium ratio (OsR), neck ratio (NR), area ratio (ArR), volume ratio (VoR), wall shear stress (WSS), normalized wall shell stress (NWSS), blood inflow, relative inflow, aneurysm average velocity, parent artery average velocity, normalized velocity, residual flow volume (RFV), and inflow concentration index (ICI); differences of these indexes before and after treatment were compared.Results:The OsR of 6 aneurysms was 0.225, 0.267, 0.265, 0.389, 1.000, 1.000, respectively; NR was 1.220, 0.274, 1.090, 1.587, 2.809, and 4.019, respectively; ArR was 0.608 and 0.224, 0.623, 3.462, 1.225 and 1.784, respectively; and VoR was 0.386, 0.052, 0.212, 3.462, 0.422 and 1.882, respectively. The parameters of WSS, NWSS, blood inflow, relative inflow, aneurysm average velocity, parent artery average velocity, normalized velocity, RFV, and ICI decreased obviously after FD implantation.Conclusion:On the basis of 3D reconstruction combined with FD/coil virtual implantation, CFD-based hemodynamic analysis can obtain accurate parameters of different types of intracranial aneurysms before and after FD treatment.

Objective:To investigate the protective effect and mechanism of Acronychia pedunculata water extracts on UV-induced light damage of human keratinocytes.Methods:The experiment was conducted from December 2018 to April 2020 in the Guangxi Medical University Laboratory of Genetics. The photoaged keratinocyte model was used, the cells were co-cultured with different concentrations of Acronychia pedunculata water extracts. The cell proliferation rate was detected by CCK-8 method. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and total antioxidant capacity (T-AOC) of cells were detected by a test kit. The levels of IL-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) were determined by ELISA.Results:The proliferation of HaCaT cells was promoted by 0.5 mg/L-2.0 mg/L of the extracts. Compared with control group, the proliferation rate of HaCaT cells in the experimental group was significantly increased ( P<0.05). Compared with control group, the contents of ROS was decreased ( F=214.67, P<0.05), MDA was decreased ( F=811.88, P<0.05), SOD was increased ( F=28.95, P<0.05), CAT was increased ( F=213.31, P<0.05), GPX was increased ( F=65.10, P<0.05), T-AOC was increased ( F=305.58, P<0.05), IL-1β was decreased ( F=15.46, P<0.05), IL-6 was decreased ( F=59.2, P<0.05), and TNF-α was decreased ( F=33.13, P<0.05). Conclusions:The extracts of 0.5-2.0 mg/L of Acronychia pedunculata have protective effects on the photoaging cell model, which may be related to the increase of SOD, CAT, GPX and other antioxidant enzymes and the level of T-AOC in photoaging HaCaT cells, and the decrease of ROS, MDA content and the expression of inflammatory cytokines.

Objective:To explore the effect of social isolation (SI) on cognitive function and the phenotypic transition of hippocampal astrocytes in mice.Methods:Twenty male C57BL/6 mice aged 3-4 weeks were randomly divided into normal group house (GH group) and social isolation group (SI Group). The mice in SI group were fed one per cage for 8 weeks to establish a social isolation model, and the mice in GH group were fed five per cage. The cognitive function of mice was detected by the novel object recognition test and novel location recognition test. The expression of astrocyte marker glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry, RT-PCR and Western blot.The astrocyte morphology change was quantitatively analyzed by Sholl Analysis.The expression of the hippocampal A1-A2 astrocytes markers proteasome subunit beta 8(PSMB8) and a member of the S100 family of Ca 2+ -binding proteins (S100A10) were determined by RT-PCR and Western blot. Statistical analysis was performed using GraphPad Prism 6.0 software, and t-test was used for comparison between two groups. Results:The results of cognitive function showed that the exploration index of novel object ((-5.54±3.30)%, (33.42±7.14)%; t=4.680, P=0.001) and the exploration index of novel location((-7.96±4.81)%, (23.55±8.20)%; t=3.670, P=0.008) in SI group were both lower than those in GH group.Immunohistochemical results showed that the number of GFAP positive cells in hippocampus of SI group was significantly lower than that of GH group((369.90±42.97), (544.90±57.64); t=2.480, P=0.023). The results of Sholl analysis showed that the protuberance of hippocampal astrocytes in SI Group retracted.There were significant differences in the number of intersections between the two groups at 6, 8, 10, 12, 14 and 16 μm away from astrocyte cell body(all P<0.05). Western blot showed that the expression of GFAP protein in SI group was lower than that in GH group((0.85±0.05), (1.03±0.06); t=2.527, P=0.028). The results of PCR showed that the expression of GFAP mRNA in SI group was lower than that in GH group ((0.83±0.05), (1.00±0.03); t=2.970, P=0.018). The expression of A1 phenotypic marker PSMB8 mRNA ((1.58±0.17), (1.00±0.06); t=2.931, P=0.011) and A2 phenotypic marker S100A10 mRNA ((1.52±0.14), (1.00±0.07); t=3.121, P=0.007) in the hippocampus of SI group were higher than those in GH group.Compared with the GH group, the expression of the neurotrophic factors IGF-1 mRNA in the SI group was down-regulated ((0.73±0.07), (1.00±0.08); t=2.327, P<0.05), while the expression of LCN2 mRNA((1.12±0.03), (1.00±0.03), t=2.575, P<0.05), IL-1β mRNA(1.76±0.19), (1.00±0.07), t=3.460, P<0.01) and TNF-α mRNA((2.18±0.42), (1.00±0.07), t=2.427, P<0.05) were up-regulated in the SI group. Conclusion:The pathological mechanism of social isolation-induced cognitive impairment in mice may be related with the phenotypic changes of astrocytes.

With the further increase of the global cancer burden, various cancers are increasingly challenging human health status and quality of life. Thus, early screening of cancer is crucial. Urinary volatile organic compounds (VOCs) detection techniques have the advantages of easy access to samples, high acceptance of patients, non-invasive, and so on, which have been favored and concerned by researchers. In this paper, existing techniques and methods for cancer diagnosis based on urine VOCs were described, relevant studies on the use of urine VOCs for cancer diagnosis were reviewed, and the barriers and future perspectives of the technique were discussed. This paper can be a reference for researchers working in the direction of urinary VOCs detection, a multidisciplinary field that spans medicine and materials science.