Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To observe the effects of Banxia Xiexin Decoction on intestinal microbes and 5-HT in ulcerative colitis(UC)model mice induced by drinking sodium dextran sulfate(DSS),and to analyze the mechanism of Banxia Xiexin Decoction in treating UC from the perspective of brain-gut axis.Methods 40 male C57BL6/J mice were randomly divided into control group,model group,positive drug(mesalazine)group and Banxia Xiexin decoction group.All mice except control group were induced by 2.5%DSS solution for 7 days to establish UC model.From the 8th day,mice in the above groups were given intragastric administration of sterilized water,mesalazine aqueous solution and Banxia Xiexin decoction aqueous solution.HE staining was used to observe histopathological changes of colon,ELISA to detect 5-HT content in serum,colon and brain tissues,and 16S rRNA sequencing to further detect the changes of fecal flora in model mice.Results Compared with model group,DAI index of experimental mice model group was significantly decreased after Banxia Xiexin Decoction intervention(P<0.05);IL-2,IL-4 and IFN-γ were significantly recovered(P<0.05).The histopathological score of proximal and distal colon was significantly decreased(P<0.01).Moreover,the peripheral 5-HT level was significantly decreased(P<0.05),but the central had an increasing trend.Results of intestinal flora showed that the relative abundance of Clostridium_sensu_stricto_1,unclassified_p__Firmicutes increased(P<0.05),while Lachnospiraceae_NK4A136_group,Lachnoclostridium,norank_f__Oscillospiraceae and Eubacterium_xylanophilum_group decreased(P<0.05).It was also found that there were significant correlations between intestinal microflora and peripheral and central 5-HT levels.Conclusion Banxia Xiexin Decoction could play a role in treating ulcerative colitis by improving the intestinal microbial composition structure of UC mice to reduce peripheral 5-HT levels and increase central 5-HT levels,thereby improving intestinal inflammatory response and relieving anxiety.

Objective:To investigate the effects of cytoplasmic fragile X mental retardation protein 1 binding protein 2 (CYFIP2) overexpression on the biological functions and Wnt/β-catenin signaling pathways of bladder cancer T24 cells.Methods:The control group was T24 cells transfected with the empty pcDNA3 vector, and the overexpression group was T24 cells transfected with the CYFIP2 overexpression vector. The expression of CYFIP2 mRNA and protein was detected by reverse transcriptase, quantitative polymerase chain reaction, and Western Blot. The effect of CYFIP2 overexpression on T24 cell proliferation was detected by CCK-8. The effect of CYFIP2 overexpression on T24 cell migration and invasion was detected by Transwell. The effects of CYFIP2 overexpression on Wnt/β-catenin signaling pathway in T24 cells were detected by Western Blot.Results:Compared with the control group, the expression levels of CYFIP2 mRNA and protein were increased in the overexpression group (all P < 0.001), and the cell proliferation, migration, and invasion abilities were reduced (all P < 0.01). β-catenin, c-Myc, and Cyclin D1 protein expression were down-regulated in CYFIP2 overexpressed T24 cells (all P < 0.05), while the protein levels of p-β-catenin were increased ( P < 0.05). Conclusions:CYFIP2 overexpression can inhibit T24 cell proliferation, migration, and invasion, and its possible molecular mechanism is related to the inhibition of Wnt/β-catenin signaling pathway.

Objective To investigate the influence from natural and constrained modal of the hip joint on internal fixation after implantation of hollow screws and locking plates for treating femoral neck fractures. Methods CT image data of a patient with femoral neck fracture were analyzed, boundary of the hip joint was extracted to generate a three-dimensional (3D) model of the hip joint, and the assembly of common internal fixation models and hip joint models was established. Finite element simulation was then conducted, with focus on vibration characteristics. Results Vibration had a certain effect on internal fixation stability of hollow screws and locking plates. The occurrence of torsion would destroy the fixation environment of hollow screws and locking plates, resulting in a small displacement at the fracture end. In a constrained state, the modal frequency range was lower. Deformation of the vibration shape mostly occurred at proximal end of the femoral head, leading to the loosening phenomenon of internal fixation and prosthesis. A method for judging the stability of internal fixation was proposed from the perspective of vibration characteristics, and it was found that the stability of internal fixation with hollow screws was better than that of proximal locking plates. Conclusions For choosing internal fixation, influences from natural frequency of the screw and plate should be considered, so as to avoid natural frequency of the femur, which may cause resonance. The results can be used as a guidance for the selection of internal fixation materials and the design of structure and configuration.

Objective:To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M 3 acute myeloid leukemia (AML) . Methods:Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors.Results:The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7% , respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group ( P<0.05) . IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS ( P<0.05) . In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS ( P<0.05) , and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4% , P=0.014) , the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2) , P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10 9/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. Conclusion:In patients with AML (non-M 3) , IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.

Objective: To analyze the dynamic changes of serum M30 and M65 levels in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) during artificial liver support system(ALSS) therapy, and to explore their predictive efficiency and clinical values for short-term prognosis of HBV-ACLF. Methods: Seventy-six patients with HBV-ACLF who underwent ALSS therapy for the first time from May 2016 to May 2019 in the First Hospital of Jiaxing were selected.The patients were divided into improvement group (38 cases) and non-recovered group (38 cases)according to their prognosis, and 38 healthy persons were selected as control group during the same period.The serum levels of M30 and M65 were detected by enzyme-linked immunosorbent assay(ELISA). The predictive values of M30 and M65 levels for short-term prognosis in patients receiving ALSS were calculated by receiver operating characteristic analysis curve (ROC). M30 and M65 levels before and after ALSS were compared by two-way repeated measures analysis of variance. Results: The levels of M30 and M65 in the improvement group, non-recovered group and control group were significantly different before the first ALSS therapy (F=109.36 and 90.42, respectively, both P<0.01). The levels of M30 and M65 were not significantly different between improvement group and non-recovered group before treatment (t=0.836 and 0.286, respectively, both P>0.05). However, after twice ALSS therapy, the levels of M30 and M65 in non-recovered group were significantly higher than those in improvement group (t=30.699 and 64.777, respectively, both P<0.01). Moreover, after the second ALSS therapy, the levels of M30 and M65 were both significantly lower compared to those after the first-time therapy in the improvement group (t=3.350 and 5.932, respectively, both P<0.01). The areas under curve (AUC) of M30, M65 and the combination of M30 and M65 for prognosis prediction were 0.796, 0.844 and 0.906, respectively. The AUC of combination of M30 and M65 was significantly higher than M30 or M65 alone (Z=2.163 and 2.141, respectively, P=0.031 and 0.032, respectively). The cut-off values of M30 and M65 were 591.91 and 924.50 U/L, respectively. The sensitivity and specificity of combined M30 and M65 were 94.7% and 82.5%, respectively. Conclusions Serum M30 and M65 levels can predict the short-term prognosis of HBV-ACLF patients after ALSS therapy.The combination of M30 and M65 is of better diagnostic value.