Engineering Assembly of Plasmonic Virus-Like Gold SERS Nanoprobe Guided by Intelligent Dual-Machine Nanodevice for High-Performance Analysis of Tetracycline.

Accurate detection of trace tetracyclines (TCs) in complex matrices is of great significance for food and environmental safety monitoring. However, traditional recognition and amplification tools exhibit poor specificity and sensitivity. Herein, a novel dual-machine linkage nanodevice (DMLD) is proposed for the first time to achieve high-performance analysis of TC, with a padlock aptamer component as the initiation command center, nucleic acid-encoded multispike virus-like Au nanoparticles (nMVANs) as the signal indicator, and cascade walkers circuit as the processor. The existence of spike vertices and interspike nanogaps in MVANs enables intense electromagnetic near-field focusing, allowing distinct surface-enhanced Raman scattering (SERS) activity. Moreover, through the sequential activation between multistage walker catalytic circuits, the DLMD system converts the limited TC recognition into massive engineering assemblies of SERS probes guided by DNA amplicons, resulting in synergistic enhancement of bulk plasmonic hotspot entities. The continuously guaranteed target recognition and progressively promoted signal enhancement ensure highly specific amplification analysis of TC, with a detection limit as low as 7.94 × 10-16 g mL-1. Furthermore, the reliable recoveries in real samples confirm the practicability of the proposed sensing platform, highlighting the enormous potential of intelligent nanomachines for analyzing the trace hazards in the environment and food.

Polyhedral Au Nanoparticle/MoOx Heterojunction-Enhanced Ultrasensitive Dual-Mode Biosensor for miRNA Detection Combined with a Nonenzymatic Cascade DNA Amplification Circuit.

A novel homologous surface-enhanced Raman scattering (SERS)-electrochemical (EC) dual-mode biosensor based on a 3D/2D polyhedral Au nanoparticle/MoOx nanosheet heterojunction (PAMS HJ) and target-triggered nonenzyme cascade autocatalytic DNA amplification (CADA) circuit was constructed for highly sensitive detection of microRNA (miRNA). Mixed-dimensional heterostructures were prepared by in situ growth of polyhedral Au nanoparticles (PANPs) on the surface of MoOx nanosheets (MoOx NSs) via a seed-mediated growth method. As a detection substrate, the resulting PAMS HJ shows the synergistic effects of both electromagnetic and chemical enhancements, efficient charge transfer, and robust stability, thus achieving a high SERS enhancement factor (EF) of 4.2 × 109 and strong EC sensing performance. Furthermore, the highly efficient molecular recognition between the target and smart lock probe and the gradually accelerated cascade amplification reaction further improved the selectivity and sensitivity of our sensing platform. The detection limits of miRNA-21 in SERS mode and EC mode were 0.22 and 2.69 aM, respectively. More importantly, the proposed dual-mode detection platform displayed excellent anti-interference and accuracy in the analysis of miRNA-21 in human serum and cell lysates, indicating its potential as a reliable tool in the field of biosensing and clinical analysis.

SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability.

SMC5/6 function in genome integrity remains elusive. Here, we show that SMC5 dysfunction in avian DT40 B cells causes mitotic delay and hypersensitivity toward DNA intra- and inter-strand crosslinkers (ICLs), with smc5 mutants being epistatic to FANCC and FANCM mutations affecting the Fanconi anemia (FA) pathway. Mutations in the checkpoint clamp loader RAD17 and the DNA helicase DDX11, acting in an FA-like pathway, do not aggravate the damage sensitivity caused by SMC5 dysfunction in DT40 cells. SMC5/6 knockdown in HeLa cells causes MMC sensitivity, increases nuclear bridges, micronuclei, and mitotic catastrophes in a manner similar and non-additive to FANCD2 knockdown. In both DT40 and HeLa systems, SMC5/6 deficiency does not affect FANCD2 ubiquitylation and, unlike FANCD2 depletion, RAD51 focus formation. SMC5/6 components further physically interact with FANCD2-I in human cells. Altogether, our data suggest that SMC5/6 functions jointly with the FA pathway to support genome integrity and DNA repair and may be implicated in FA or FA-related human disorders.

High phosphate-induced downregulation of PPARγ contributes to CKD-associated vascular calcification.

Medial arterial calcification associated with hyperphosphatemia is a main cause of cardiovascular mortality in patients with chronic kidney disease (CKD), but the mechanisms underlying high phosphate-induced vascular calcification remain largely unknown. Here, we observed a significant decrease in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in calcified arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia. In vitro, high phosphate treatment led to a decreased expression of PPARγ in mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic differentiation and calcification. Pretreatment with PPARγ agonist rosiglitazone significantly reversed high phosphate-induced VSMCs calcification. Further investigation showed that methyl-CpG binding protein 2 (Mecp2)-mediated epigenetic repression was involved in high phosphate-induced PPARγ downregulation. Moreover, the expression of Klotho that has the ability to inhibit vascular calcification by regulating phosphate uptake decreased with the PPARγ reduction in VSMCs after high phosphate treatment, and rosiglitazone failed to inhibit high phosphate-induced calcification in VSMCs with knockdown of Klotho or in aortic rings from Klotho-deficient (kl/kl) mice. Finally, an in vivo study demonstrated that oral administration of rosiglitazone could increase Klotho expression and protect against high phosphate-induced vascular calcification in CKD mice. These findings suggest that the inhibition of PPARγ expression may contribute to the pathogenesis of high phosphate-induced vascular calcification, which may provide a new therapeutic target for vascular calcification in CKD patients.

Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis.

Fanconi anemia (FA) is an autosomal or X-linked human disease, characterized by bone marrow failure, cancer susceptibility and various developmental abnormalities. So far, at least 22 FA genes (FANCA-W) have been identified. Germline inactivation of any one of these FA genes causes FA symptoms. Proteins encoded by FA genes are involved in the Fanconi anemia pathway, which is known for its roles in DNA inter-strand crosslinks (ICLs) repair. Besides, its roles in genome maintenance upon replication stress has also been reported. Post-translational modifications (PTMs) of FA proteins, particularly phosphorylation and ubiquitination, emerge as critical determinants in the activation of the FA pathway during ICL repair or replication stress response. Consequent inactivation of the FA pathway engenders heightened chromosomal instability, thereby constituting a genetic susceptibility conducive to cancer predisposition and the exacerbation of tumorigenesis. In this review, we have combined recent structural analysis of FA proteins and summarized knowledge on the functions of different PTMs in regulating FA pathways, and discuss potential contributions stemming from mutations at PTMs to the genesis and progression of tumorigenesis.

Explore the Pattern of Biomechanical Alterations in Vocal Fold Scar and Its Objective Quantitative Assessment Method.

OBJECTIVES: This research aims to discern the evolving nature of the biomechanical properties of vocal fold scarring by calculating Young's modulus for the vocal fold cover layer, the body layer, and the structure as a whole. The study also investigates the potential of diffusion tensor imaging (DTI) for determining these biomechanical characteristics quantitatively. METHODS: A total of six adult female Beagles were divided into two groups (A and B groups) for the creation of unilateral vocal fold scar models, each group containing three subjects. Five months postmodel creation, larynxes were excised and placed within a 9.4T BioSpec MRI system (Bruker, Germany) for scanning. Subsequently, the vocal folds were segregated from the larynx. In A group of Beagles, the vocal fold cover layer and body layers were separated, whereas in B group they remained intact. All samples were then subjected to cyclic tensile testing using an Instron MicroTester 5948, with Young's modulus computed for the vocal fold cover layer and body layers in the A group and for the intact vocal fold in the B group. Differences in the overall Young's modulus between the vocal fold scarred side and the healthy side were analyzed, and a Pearson correlation analysis was performed between DTI parameters and the outcomes of the stress-strain experiments. RESULTS: A statistically significant discrepancy in the overall Young's modulus was identified between the scar and healthy sides of the vocal fold (P = 0.0401). The Young's modulus also displayed a significant difference between the scar and healthy sides of the vocal fold cover layer (P = 0.0241). No meaningful divergence was observed in the elastic modulus between the scar and healthy sides of the vocal fold body layer (P > 0.05). Postseparation, Young's modulus for both the cover and body layers of the scarred vocal fold were less than that of the same layers on the healthy side. However, Young's modulus of the entirety of the vocal fold on the scar side was greater than that of the whole vocal fold on the healthy side. The fractional anisotropy (FA) of the vocal fold cover layer had a significant correlation with the elastic modulus (r = 0.812, P = 0.050), as did the Tensor trace (r = -0.821, P = 0.045). The FA of the vocal fold body layer showed no significant correlation with the elastic modulus (r = -0.725, P = 0.103), while the Tensor trace demonstrated a significant correlation (r = 0.911, P = 0.012). CONCLUSIONS: Biomechanical alterations in vocal fold scars demonstrate a closer association with adhesion bands, thus emphasizing the importance of adhesion band loosening for the restoration of vibratory function within vocal fold scarring. DTI emerges as a potent noninvasive quantitative instrument for assessing these biomechanical changes, as well as for quantitatively gauging the severity of vocal fold scarring.

[Analysis of vocal fold movement characteristics in patients with laryngeal neurogenic injury].

Objective:To analyze the characteristics of vocal fold movement and glottic closure in patients with laryngeal neurogenic injury. Methods:A total of 185 patients with vocal fold paralysis diagnosed by laryngeal electromyography as neurogenic damage to cricothyroid muscle, thyreoarytenoid muscle and posterior cricoarytenoid muscle were enrolled, they were divided into unilateral vocal fold paralysis group and bilateral vocal fold paralysis group, respectively, and superior laryngeal paralysis group, recurrent laryngeal nerve paralysis group and vagal nerve paralysis group according to nerve injury. The characteristics of vocal fold movement and glottic closure were analyzed under strobe laryngoscope. The qualitative evaluation of vocal fold movement was fixed vocal fold, reduced vocal fold movement and normal vocal fold movement, and the qualitative evaluation of glottic closure was glottic closure and glottic imperfection. The results were analyzed statistically. Results:The proportion of normal, reduced and fixed vocal fold motion in bilateral vocal fold paralysis group was significantly different from that in unilateral vocal fold paralysis group（P<0.05）, the composition of normal and reduced vocal fold motion in bilateral vocal fold paralysis group（47.70%） was significantly greater than that in unilateral vocal fold paralysis group（12.27%）. There was no significant difference between the proportion of glottic closure and glottic imperfecta in bilateral vocal fold paralysis group and unilateral vocal fold paralysis group（P<0.05）. The proportion of decreased vocal fold motion in superior laryngeal nerve paralysis group（50.00%） was higher than that in recurrent laryngeal nerve paralysis group（9.32%） and vagal nerve paralysis group（9.00%）. The proportion of decreased and fixed vocal fold motion in superior laryngeal nerve paralysis group, recurrent laryngeal nerve paralysis group and vagal nerve paralysis group was statistically significant（P<0.05）.There was no significant difference in glottic closure among the three groups（P<0.05）. Conclusion:Vocal fold movement characteristics of patients with laryngeal neurogenic injury were mainly vocal fold fixation, or normal or weakened vocal fold movement. There may be missed diagnosis of unilateral vocal fold paralysis in clinical practice. In half of the patients with superior laryngeal nerve palsy, vocal fold movement is characterized by vocal fold fixation.

Targeted-activation superparamagnetic spherical nucleic acid nanomachine for ultrasensitive SERS detection of lysozyme based on a bienzymatic-mediated in situ amplification strategy.

Lysozyme (LYS) is a widely used bacteriostatic enzyme. In this paper, we built a sensitive and accurate Raman biosensing platform to detect trace amounts of LYS. The method is based on magnetic spherical nucleic acid formed by a combination of LYS aptamer (Apt) and magnetic beads (MBs). Meanwhile, this method utilizes a dual enzyme-assisted nucleic acid amplification circuit and surface-enhanced Raman scattering (SERS). In this sensing strategy, which is based on the specific recognition of Apt, magnetic spherical nucleic acids were associated with SERS through a nucleic acid amplification circuit, and the low abundance of LYS was converted into a high-specificity Raman signal. Satellite-like MB@AuNPs were formed in the presence of the target, which separated specifically in a magnetic field, effectively avoided the interference of complex sample environment. Under the optimal sensing conditions, the concentration of LYS exhibited a good linear relationship between 1.0 × 10-14 and 5.0 × 10-12 M and the limit of detection was as low as 8.3 × 10-15 M. In addition, the sensor strategy shows excellent accuracy and sensitivity in complex samples, providing a new strategy for the specific detection of LYS.

Using Diffusion Tensor Imaging to Explore the Changes in the Microstructure of Canine Vocal Fold Scar Tissue.

OBJECTIVE: To apply diffusion tensor imaging (DTI) in measurement of the diffusion characteristics of water molecules in vocal fold scar tissue, combined with the analysis of textural characteristics of collagen fibers in the cover layer of the vocal folds to explore the feasibility of DTI in the qualitative and quantitative diagnosis of vocal fold scars and the evaluation of microstructural changes of vocal fold scar tissue. METHODS: A unilateral injury was created using micro-cup forceps in the left vocal fold of six beagles. The contralateral normal vocal fold was used as a self-control. Five months postinjury, the larynges were excised and placed into a magnetic resonance imaging (MRI) system (9.4T BioSpec MRI, Bruker, German) for scanning and extraction of the diffusion parameters, fractional anisotropy (FA) and tensor trace in the anterior, middle, and posterior portions of the vocal fold cover layer. These parameters were then analyzed for statistical significance between the scarred vocal fold and the normal vocal fold. After MRI scanning, the tissue of the vocal folds was divided into anterior, middle, and posterior parts for sectioning and staining with hematoxylin and eosin, and samples were subsequently digitally scanned for texture analysis. The irregularity parameters, energy, contrast, correlation, and homogeneity, of collagen fibers of the vocal folds and the mean gray value of collagen fibers were calculated by the gray-level co-occurrence matrix (GLCM) texture analysis method. The differences in the mean value of the two sides of the vocal fold were compared. In addition, Pearson correlation analysis was performed between DTI parameters and irregularity parameters. RESULTS: The FA of the left vocal fold cover layer was significantly lower compared to the self-control group (P = 0.0366), and the tensor trace value on the left vocal fold cover layer was significantly higher compared to the self-control group (P = 0.0353). The FA was significantly higher in the anterior part of the right vocal fold cover layer compared to the middle and posterior parts of the same side (P = 0.0352), and the tensor trace was significantly lower in the anterior part of the right vocal fold cover layer compared to the middle and posterior parts of the same side (P = 0.0298). There were no significant differences in FA and tensor trace between the middle and posterior parts of the vocal fold cover layer. The mean gray value of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P = 0.0219), the energy of the left vocal fold cover layer was significantly smaller than that of the right vocal fold cover layer (P < 0.0001), the contrast of the left vocal folds cover layer was significantly larger than that of the right vocal fold cover layer (P = 0.0002), the correlation of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P = 0.0002), and the homogeneity of the left vocal folds cover layer was significantly smaller than the right vocal fold cover layer (P = 0.0003). Pearson correlation analysis yielded values of r = 0.926, P = 0.000 between the FA and mean gray value; r = -0.918, P = 0.000 between FA and energy; r = -0.924, P = 0.000 between the FA and homogeneity, r = -0.949, P = 0.000 between tensor trace and mean gray value; r = 0.893, P = 0.000 between the tensor trace and energy; and r = 0.929, P = 0.000 between the tensor trace and homogeneity. CONCLUSION: FA and tensor trace can be used as effective parameters to reflect microstructural changes in vocal fold scars. DTI is an objective and quantitative method of analyzing vocal fold scarring, and it noninvasively evaluates the microstructure of vocal fold collagen fibers.

Increased 18F-FDG Uptake in the Posterior Region of Contralateral Vocal Folds in Beagle Dogs With Unilateral Vocal Fold Immobility Disorders.

OBJECTIVE: To explore the glycolytic metabolism of contralateral vocal fold compensation by examining the glycolytic metabolism of the posterior region of vocal folds in beagles with unilateral vocal fold immobility disorders and its correlation with acoustic parameters. STUDY DESIGN: Prospective animal study. SETTING: Department of Voice METHODS: Ten adult beagles were divided randomly into three groups: a unilateral cricoarytenoid joint dislocation (UCAJD) group (n = 4), a unilateral vocal fold paralysis (UVFP) group (n = 4), and a control group (n = 2). Positron emission tomography-computed tomography (PET/CT) scans of larynx and recordings of vocalizations were collected 4 months after the operations. The maximum standardized uptake values (SUVmax) of 18F-FDG within each posterior region of the vocal folds were obtained from PET/CT and voice recordings were analyzed for acoustic parameters F0, jitter, shimmer, and loudness using PRAAT. RESULTS: In both UCAJD and UVFP groups, a significant increase of SUVmax was observed in the contralateral vocal fold relative to the impaired fold (P < 0.05). The SUVmax values of the contralateral vocal folds and the SUVmax values of the impaired vocal folds in the UCAJD, UVFP, and control groups were both found to be significantly different (P < 0.05). The SUVmax of the contralateral vocal fold may exhibit a potentially negative correlation with jitter and shimmer, with R2 values of 0.42 and 0.26 and P values of 0.03 and 0.11, respectively. CONCLUSION: UCAJD and UVFP can cause enhanced glycolytic metabolism of the contralateral vocal fold relative to the impaired vocal fold. The SUVmax of the contralateral vocal fold may be positively correlated with acoustic quality.

Vocal Vibration Opening Onset Position Abnormality in Patients With Adductor Spasmodic Dystonia by Using High-Speed Endoscopy.

OBJECTIVE: To analyze vocal fold vibration onset in patients with adductor laryngeal dystonia (ADLD) by analyzing vocal vibration opening onset position (VVOOP). STUDY DESIGN: Case-control study SETTING: A voice center. METHODS: Eleven patients with ADLD diagnosed in our voice center were enrolled in the ADLD group. Eleven healthy subjects matched by exact age and gender to the ADLD patients were selected as the control group. All subjects underwent laryngeal high-speed video endoscopy. VVOOP and its change were assessed by two otolaryngologists. The multiline video kymography was used to analyze the open quotient (OQ) and standard deviation of OQ. RESULTS: VVOOP had more than one position in 54.6% (6/11) of the patients with ADLD, which was higher than the control group (P < 0.05). VVOOP appeared in the front of the vocal fold in 54.6% (6/11) of patients with ADLD and in the back of the vocal fold in 81.8% (9/11) of patients with ADLD. VVOOP can be abnormal in 90.9% (10/11) of patients with ADLD, and the rate of VVOOP abnormality was higher than that of the control group (P < 0.05). Of 11, 6 (54.6%) patients with ADLD had a variable VVOOP; the variability rate of VVOOP was higher than that in the control group (P < 0.05). OQ and OQ standard deviation in the ADLD group were significantly greater than in the control group (P < 0.05). CONCLUSIONS: In patients with ADLD, vocal fold vibration was irregular, and VVOOP was abnormal and had a variable position and could reflect variability of the vocal vibration. LEVEL OF EVIDENCE: Level 4.

To Explore the Changes and Differences of Microstructure of Vocal Fold in Vocal Fold Paralysis and Cricoarytenoid Joint Dislocation by Diffusion Tensor Imaging.

OBJECTIVE: The diffusion characteristics of water molecules were measured in the vocal folds of canines exhibiting unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation. These characteristics were used in conjunction with a histological examination of the microstructural changes of vocal fold muscle fibers to explore the feasibility of diffusion tensor imaging (DTI) in distinguishing unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation as well as evaluating microstructural changes. METHODS: Ten beagles were randomly divided into three groups: four in the unilateral vocal fold paralysis group, four in the unilateral cricoarytenoid joint dislocation group, and two in the normal group. Unilateral recurrent laryngeal nerve resection was performed in the vocal fold paralysis group. Unilateral cricoarytenoid joint dislocation surgery was performed in the dislocation group. No intervention was performed in the normal group. Four months postintervention, the larynges were excised and put into a magnetic resonance imaging (MRI) system (9.4T BioSpec MRI, Bruker, German) for scanning, followed by an analysis of diffusion parameters among the different groups for statistical significance. After MRI scanning, the vocal folds were cut into sections, stained with hematoxylin and eosin, and scanned digitally. The mean cross-sectional area of muscle fibers, and the mean diameter of muscle fibers in the vocal folds were calculated by target detection and extraction technology. Mean values of each measurement were used to compare the differences among the three groups. Pearson correlation analysis was performed on the DTI parameters and the results from histological section extraction. RESULTS: The paralysis group had significantly higher Fractional Anisotropy (FA) compared to the dislocation group and normal group (P = 0.004). The paralysis group also had a significantly lower Tensor Trace value compared to the dislocation group and normal group (P = 0.000). The average cross-sectional area of vocal fold muscle fibers in the paralysis group was significantly smaller than the dislocation group and normal group (P = 0.000). Pearson correlation analysis yielded values of, r = -0.785, P = 0.01 between the average cross-sectional area of vocal muscle fibers and FA, and values of r = 0.881, P = 0.00 between Tensor Trace and the average cross-sectional area of vocal muscle. CONCLUSION: FA and Tensor Trace can be used as effective parameters to reflect the changes of microstructure in vocal fold paralysis and cricoarytenoid joint dislocation. DTI is an objective and quantitative method to effectively evaluate unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation, also capable of noninvasively evaluating vocal fold muscle fiber microstructure.

The Influence of Voice Training on Vocal Learner's Objective Acoustic Voice Components.

OBJECTIVE: Acoustic parameters of voice were studied in music majors throughout 18 months of training to understand the influence of voice training on voice. METHODS: Twenty-three students from Xiamen Music School between 12 and 15 years old were enrolled. Acoustic examination was performed three times- every 6 months for 18 months. Various traditional acoustic parameters were measured, including dysphonia severity index (DSI), jitter, and D-value of vocal range. Nonlinear dynamic measures were also measured, including diffusive chaos to construct voice type component profiles (VTCPs), spectrum convergence ratio, and nonlinear energy difference ratio. The results were analyzed by multivariate analysis of variance. RESULTS: Over the study duration, there was an improvement of DSI (P = 0.002), and D-value of vocal range (P = 0.000). Among nonlinear parameters, only voice type component data demonstrated significant changes during the study duration. Both Voice Type Component 1(VTC1) and VTC3 values differed from Time 1 to Time 2 as well as from Time 1 to Time 3. The proportion of VTC1 in samples generally decreased, while VTC3, representative of aperiodicity, increased. Both nonlinear energy difference ratio and spectrum convergence ratio exhibited no significant changes throughout the study. CONCLUSION: Professional voice training can improve DSI and D-value of vocal range in singers' voices. These parameters have potential to be used for voice training evaluation and screening. Many nonlinear parameters did not detect differences in the healthy voices studied, but VTCPs created using intrinsic dimension present a valuable new method, visualizing increases in aperiodicity of the speaking voices after professional voice training.

Munro Pressure Ulcer Risk Assessment Scale in Adult Patients Undergoing General Anesthesia in the Operating Room.

Pressure ulcers are a common complication of immobility and frequently occur in surgical patients. The occurrence of pressure ulcers is affected by many factors, such as operation time and position, anesthesia method, and postoperative nursing. The aim of this study was to investigate the Munro Pressure Ulcer Risk Assessment Scale's value in predicting acute pressure ulcers in general anesthesia patients. This case-control study included patients who underwent more than 2 hours of general anesthesia in our hospital from January 2018 to December 2020. The case group comprised 42 patients who had pressure sores in surgical compression sites within 3 days after surgery. The control group consisted of 84 patients without acute pressure sores after surgery. Baseline patient data were compared between the two groups, and a logistic multivariate model was used to analyze potential risk factors for acute pressure ulcers. The Munro Pressure Ulcer Risk Assessment Scale scores and Braden scale scores were compared between the two groups during and after surgery. A receiver operating characteristic curve was used to evaluate the clinical value of the two scales (administered at the two time points) in predicting the occurrence of acute pressure ulcers after surgery. The operation and anesthesia times of patients in the case group were longer than those in the control group (P < 0.05). The proportion of comatose patients and patients with diabetes were significantly higher in the case group. While the case group had higher Munro scores during and after surgery compared to the control group (P < 0.05), Braden scores at the corresponding time points were lower (P < 0.05). The following variables were identified as independent risk factors of acute pressure ulcers: prolonged operation time and anesthesia time, increase in Munro scores during and after operation, decrease in Braden scores during and after operation, and comatose status (P < 0.05). The area under the receiver operating characteristic curve (AUC) of the postoperative Munro score for predicting postoperative pressure ulcer risk was 0.774; the sensitivity and specificity were 67.73% and 80.58%, respectively. The AUC of the intraoperative Braden score for predicting postoperative pressure ulcer risk was 0.836, with a sensitivity of 78.95% and specificity of 78.00%. The AUC of the postoperative Braden score for predicting postoperative pressure ulcer risk was 0.809, with a sensitivity of 73.58% and specificity of 64.26% (P < 0.05). Our results indicate that the intraoperative Munro Pressure Ulcer Risk Assessment Scale is highly effective for predicting the risk of postoperative pressure ulcers in surgical patients who require general anesthesia.

Application of 4D-CT Scanning in Differential Diagnosis of Arytenoid Subluxation and Vocal Fold Paralysis.

OBJECTIVE: To differentiate arytenoid subluxation and vocal fold paralysis by CT cine mode scanning combined with three-dimensional (3D) reconstruction image. METHODS: Seventy-six patients with suspected vocal fold dyskinesia were collected. All patients were examined being asked to inhale deeply and then make "Yi" sound continuously during CT scanning with cine mode. The optimal maximum opening and minimum closing phases of glottis were selected and 3D reconstruction images were performed. The length of vocal fold, the width of glottis, and the subglottal convergence angle, anteversion angle, elevation angle, valgus angle, and varus angle of cricoarytenoid joints were measured. Vocal fold deformation was divided into three types: type I, type II, and type III. Kappa test was used to compare the consistency between CT diagnosis and clinical diagnosis. Single-factor analysis of variance was used to analyze the statistical differences among arytenoid subluxation, vocal fold paralysis, and normal vocal fold. RESULTS: There was high consistency between CT diagnosis and clinical diagnosis (k = 0.731, P < 0.05), as well as significant differences in the opening width of glottis between type I and type III, the valgus and varus angles of cricoarytenoid joints between type I and type II or type III, and the subglottal convergence angles among the three types of vocal fold deformation. CONCLUSIONS: CT scanning with cine mode combined with 3D reconstruction can display the changes of larynx structures in vocal fold dyskinesia, and can be used for the differential diagnosis of arytenoid cartilage subluxation and vocal fold paralysis.

The Influence of Voice Training on Vocal Learners' Supraglottal Activities and Aerodynamic Evaluation.

OBJECTIVE: Among music majors with only 18 months of training, supraglottal activities and aerodynamic parameters were studied to facilitate understanding of the influence of voice training on characteristics of voice production. METHODS: Twenty-three students at the Xiamen Music School were examined over the course of 18 months of singing training. Only 17 students completed all data collection sessions. All students had no previous voice training and were confirmed to be without organic voice disorders by a laryngologist but did present with supraglottal compression. Strobolaryngoscopy and aerodynamic assessment were performed every 6 months. Using the laryngoscopic images, anterior-posterior (A-P) compression and medial-lateral compression were analyzed. Aerodynamic assessment was carried out to measure maximum phonation time, phonation threshold flow, glottal resistance, subglottal pressure, phonation threshold pressure, and vocal efficiency. From these measurements, the mean was calculated along with a measurement of reliability. One-way ANOVA with Bonferroni post hoc test was used to evaluate the results between subjects at different time points. Kendall's W test was completed to assure consistency between and within laryngologists. RESULTS: Referring to the Strobolaryngoscopy Evaluation Rating Form, 4 of the 17 students had decreased A-P compression scores in the second measurement compared to the first (from 2.24 ± 0.20 to 2.12 ± 0.17, P = 0.100). After completion of the program, 6 of the 17 students' anterior-posterior compression scores further improved from the second measurement (from 2.12 ± 0.17 to 1.71 ± 0.17, P = 0.600). The A-P compression scores showed a gradual downward trend and was overall statistically significant (P = 0.004). In addition, there was an improvement of maximum phonation time (P​ ​= 0.016). CONCLUSION: Professional voice training can improve the supraglottal activities and maximum phonation time. These parameters have potential to be used for voice training evaluation and screening.

The Effects of Hard Voice Onset on Objective Voice Function in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: Laryngopharyngeal reflux (LPR) causes laryngopharyngeal hypersensitivity and laryngeal muscle hyperfunction, which may result in hard voice onset in patients with LPR. The purpose of this study is to examine the incidence of hard voice onset in patients with LPR and the effects of hard voice onset on objective voice function in patients with LPR. METHODS: Forty patients with confirmed LPR were enrolled in the LPR group, and 40 healthy subjects were enrolled in the non-LPR group. Subjects underwent laryngeal high-speed videoendoscopy, and the presence or absence of hard voice onset in each subject was determined by two experienced laryngologists based on whether glottal closure was complete or incomplete before vocal fold vibration. Based on the results, the subjects with LPR were divided into a hard voice onset group and a non-hard voice onset group. The voice onset time (VOT) was measured and compared between the hard and non-hard voice onset groups within the LPR group. Laryngeal aerodynamic assessment was also carried out on the LPR group, and subglottal pressure, phonation threshold pressure (PTP), glottal resistance, and mean flow rate were measured. The voice acoustic signals of subjects were additionally analyzed in the LPR group, and the fundamental frequency, jitter, shimmer, and noise-harmony ratio were determined. The kappa statistic, chi-square test and independent-samples t test in SPSS were used for statistical analysis. RESULTS: The two laryngologists had substantial inter-rater consistency on the evaluation of hard voice onset and non-hard voice onset, with a kappa statistic of 0.71. In the LPR group, 42.5% of patients had hard voice onset (17/40), significantly more than in the non-LPR group (8/40, 20%) (P < 0.05). The VOT in the LPR group was significantly longer than in the non-LPR group (P < 0.05). Within the LPR group, the VOT, PTP and shimmer were significantly greater in the hard voice onset group than in the non-hard voice onset group (all P < 0.05). The other laryngeal aerodynamic parameters and acoustic parameters were not significantly different between the hard voice onset group and the non-hard voice onset group (P > 0.05). CONCLUSION: Changes in vocal production may occur in LPR patients, causing them to be more susceptible to hard voice onset. The patients with hard voice onset require longer VOT and greater PTP to initiate phonation.

Glottic Insufficiency in the Vertical Plane in Patients With Unknown-Source Unilateral Vocal Fold Hypomobility.

OBJECTIVE: To observe the laryngeal CT and strobe laryngoscopy signs of unilateral vocal fold hypomobility (UVFHM) in patients with well-closed glottises in the horizontal plane. METHODS: A retrospective analysis was performed on 18 subjects with well-closed glottises in the horizontal plane using strobe laryngoscopy, 9 patients diagnosed with unilateral vocal fold hypomobility with an unknown etiology were enrolled in the UVFHM group, and 9 healthy matched subjects with symmetrical bilateral vocal fold movement were enrolled in the control group. Vertical plane distances of bilateral vocal folds and three-dimensional structural parameters of vocal folds were measured through laryngeal CT. Glottic insufficiency in the vertical plane and reflux findings scores (RFS) were assessed under laryngeal CT and strobe laryngoscopy. Reflux symptom index (RSI) were collected. SPSS25.0 software was used for statistical analysis. RESULTS: The height differences in vertical plane and thicknesses of bilateral vocal folds in the UVFHM group were larger than those in the control (P < 0.05), while the length, width and subglottic convergence angle of the vocal folds were not statistically significant between the two groups (P > 0.05). In the UVFHM group, laryngeal CT showed that 77.78% of patients (7/9) had glottic insufficiency in the vertical plane, with height differences ranging from 0.3 to 1.9 mm and a mean of 0.76mm. However, strobe laryngoscopy showed that 33.33% (3/9) had glottic insufficiency in the vertical plane. The proportion of patients with glottic insufficiency in vertical plane in the UVFHM group was significantly higher than that in the control group (P < 0.05). RSI and RFS scores of the UVFHM group were higher than those of the control group (P < 0.05). CONCLUSION: Glottic insufficiency in the vertical plane often occurred in patients with UVFHM with an unknown cause of hoarseness, so the presence of glottic insufficiency in the vertical plane should be considered when hoarseness is detected by clinicians. Laryngeal dynamic CT can enhance the diagnostic rate compared to strobe laryngoscopy. Unexplained UVFHM patients have higher RSI and RFS compared to control subjects, warranting further research about the relationship between UVFHM and laryngopharyngeal reflux.

Compensatory Movement of Contralateral Vocal Folds in Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES: Previous studies of subjects with unilateral vocal fold paralysis (UVFP) as observed in a positron emission tomography-computed tomography (PET-CT) examination have demonstrated false positive results in the contralateral cricoarytenoid, in which the metabolism may be higher. This area may also be the site of contralateral compensatory movement in these patients. In this study, we compared the adduction speed of the contralateral vocal folds in patients with UVFP and in healthy subjects as measured by the stroboscopic laryngoscope frame rate. This study aimed to explore the contralateral compensatory movement of the vocal folds in subjects with UVFP. METHODS: (1) We collected visual data from 14 patients with UVFP and 14 healthy subjects through a stroboscopic laryngoscope. These subjects were divided into a vocal fold paralysis group and a control group, and we analyzed the excessive adduction of the contralateral vocal folds in the vocal fold paralysis group by examining vocal fold movement speed (pixels/s) as featured in a stroboscopic laryngoscope video. (2) We analyzed the uptake of 18-FDG in the posterior vocal fold from positron emission tomography-computed tomography imaging from four subjects with UVFP and 12 healthy subjects. An independent sample t test and a χ2 test were used to compare data. RESULTS: Four subjects with UVFP had a higher metabolic rate in the contralateral cricoarytenoid joints, with a significant difference between the two groups, P < 0.05. Fifty percent of the cases of contralateral adduction of the vocal folds in the subjects with UVFP adducted past the midline, with a significant difference between the two groups, P < 0.05. The contralateral adduction of the vocal folds in subjects with UVFP had shorter video frames and higher adduction speed than the control group, and the difference was statistically significant, P < 0.05. There were fewer vocal fold abduction video frames and higher abduction speed of the healthy side of the vocal fold in subjects with UVFP than the control group, but there was no statistically significant difference, P > 0.05. CONCLUSION: Subjects with UVFP exhibited faster adduction compensation in the contralateral vocal folds, and the contralateral cricoarytenoid joint's metabolism in subjects with UVFP was higher. These data may help clarify the diagnostic criteria for laryngeal nerve damage.

Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1-BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.