OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Ultrasound technology has been applied in the biomedical field,particularly in drug delivery and cell processing.In this study,the effects of different ultrasound power levels(40 W to 100 W)and time durations(1 min,5 min,or 5 min discontinuously)on the morphology of human red blood cells(hRBCs)membranes were systematically investigated using cryo-electron tomography(Cryo-ET).The hRBCs membranes were firstly subjected to ultrasound at power levels of 40 W and 60 W for 5 min each.Cryo-ET observations revealed minimal morphological changes in the hRBCs membranes following the 40 W treatment,with the membrane structure remaining relatively intact and only minor undulations appearing on the membrane surface.These undulations might result from the mild mechanical stress induced by ultrasound,which was insufficient to disrupt the overall membrane structure.At power of 60 W,the hRBCs membranes largely preserved their structural integrity.When the ultrasonic power was increased to 80 W,the structural damage to the hRBCs membranes became more severe.Cryo-ET images showed irregular ruptures and larger pores on the membrane surface,indicating a significant compromise in membrane integrity.At ultrasound power of 100 W,the hRBCs membranes were completely disrupted,resulting in the formation of numerous membrane fragments,and a complete loss of membrane continuity.To further explore the effects of ultrasound duration on erythrocyte membrane morphology,the ultrasonic power was fixed at 100 W and the impacts of varying treatment durations(1 min,5 min,and intermittent ultrasound)on the membrane structure were systematically investigated.After 1 min of ultrasonic treatment,Cryo-ET images showed minimal changes in erythrocyte membrane morphology.Although some small pores and undulations appeared on the membrane surface,the overall structure remained relatively intact.As the ultrasound duration extended to 5 min,the degree of membrane damage increased significantly.Cryo-ET images revealed extensive rupture and detachment of the membrane,with continuity being severely compromised.As to treatment alternating 1 min of ultrasound with 1 min of rest,for a total of 5 min of ultrasound exposure,Cryo-ET observations showed the integrity of the membrane-cytoskeleton attachment remained.Under intermittent ultrasound treatment,although some pores and ruptures were observed on the membrane surface,the overall structure remained more intact compared to continuous ultrasonic treatment.This preservation might be due to the intermittent treatment providing buffer periods for the membrane,allowing partial recovery after mechanical stress,thereby reducing the cumulative damage caused by continuous ultrasound.This work provided experimental basis for further understanding of mechanism of ultrasound induced change of cell membrane and cytoskeleton.

Objective To explore the application value of fractional anisotropy(FA)analysis of RGB component transformation in different directions of fibers in substantia nigra in Parkinson's disease(PD).Methods There were 35 cases of PD and 37 cases of normal control group.After being performed by brain diffusion tensor imaging(DTI)scanning,the sequence was imported into 3DSlicense 5.6.0,and the diffusion module was used to implement pseudo color mapping based on FA,locate and segment substantia nigra,and use the substantia nigra mask as the tracking starting point.After forming tracing,fibers were imported into DTIANALYSIS 1.51,converting the RGB components into FA values for analysis,and visualized the analysis result.At the same time,fiber length,fiber density,and segmented FA point cloud percentage were compared.Results Compared with the normal group,the length of substantia nigra fibers in the PD group was shorter[(95.14±19.85)mm vs(115.99±21.39)mm,P＜0.01],and there was a statistical difference between the two groups.There was no statistical difference in fiber density[(0.07±0.05)/mm3 vs(0.10±0.12)/mm3,P＞0.05]between control group and PD group.The percentage of FA segment point clouds in the PD group was lower than that in the normal group at 0.9-1,but the principal component characteristics of the point cloud ratios in each FA segment were not significant.Conclusion Based on the transformation of RGB components into FA analysis,the length,density,and FA values of substantia nigra nerve fibers in PD patients can be quantified and visualized,providing a basis for the study of PD neural pathways.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To investigate the impact of a history of atopy on the value of fractional exhaled nitric oxide (FENO) for predicting sputum eosinophils in patients with chronic cough. METHODS: A total of 868 patients with persistent cough lasting more than 3 weeks without pulmonary infection were enrolled, including 119 patients with subacute cough (defined as cough lasting 3-8 weeks) and 749 with chronic cough (longer than 8 weeks). The predictive value of FENO level for sputum eosinophilia was analyzed using receiver-operating characteristic (ROC) curve analysis, and the area under the curve (AUC) was calculated. The atopy status of the patients was determined by screening for history of allergy, hay fever, or animal or food allergies. RESULTS: Of the 868 patients enrolled, 173 patients (19.9%) had eosinophilic airway inflammation (EAI). In the overall patients, the median (Q1, Q3) FENO level was 18 (12, 35) ppb, ranging from 5 to 300 ppb. The patients with chronic cough and a positive history of atopy had a higher median FENO level than those without atopy (24 [13, 50] vs 18 [11, 34]; Z=2.25, P= 0.029), and FENO level was significantly correlated with EAI (r=0.281, P < 0.001). The AUCs of FENO for diagnosis of airway eosinophilia in patients with atopy and those without atopy were 0.677 (95% CI: 0.548-0.806) and 0.708 (95% CI: 0.660-0.756), respectively. The optimal cut-off value of FENO for diagnosing EAI was higher in patients with atopy than in those without atopy (72 vs 28.5 ppb). CONCLUSION A history of atopy reduces the predictive value of FENO level for EAI in patients with chronic cough, suggesting the importance of examining the atopic status when interpreting test results of FENO.
Humans ; Cough/diagnosis* ; Exhalation ; Fractional Exhaled Nitric Oxide Testing ; Nitric Oxide/analysis* ; Eosinophilia ; Chronic Disease ; Inflammation

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*