Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective To investigate the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)combined with Doppler ultrasound and elastography in breast lesions.Methods A total of 91 patients with breast lesions confirmed by pathology were retrospectively selected and underwent DCE-MRI,Doppler ultrasound and elastography examinations.The imaging features of benign and malignant breast lesions were analyzed.The diagnostic value of DCE-MRI,Doppler ultrasound,and elastogra-phy in benign and malignant breast lesions were analyzed.Results Among the 91 cases,there were 62 cases with benign lesions(benign group)and 29 cases with malignant lesions(malignant group).There were statistically significant differences in DCE-MRI parameters,Doppler ultrasound parameters and elastography parameters between the two groups(P<0.05).Binary logistic regres-sion analysis found that enhancement characteristics,morphology,time-signal intensity curve(TIC),blood flow signals on Doppler ultrasound,elastography score,and strain rate(SR)were the influencing factors of benign and malignant breast lesions(P<0.05).The differential diagnostic efficacy of combination of the three examinations was highest.The sensitivity,specificity and accuracy were 88.71%,82.76%and 86.81%,respectively.Conclusion DCE-MRI,Doppler ultrasound,and elastography are effective for differentiating benign and malignant breast lesions.Combination of them can improve the diagnostic performance.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

Objective:To investigate the clinicopathological characteristics and diagnosis of high-grade succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC).Methods:Three cases of high-grade SDH-RCC diagnosed by immunohistochemical staining and/or molecular testing were collected from Affiliated Hospital of Qingdao University and 971 Hospital of Navy of Chinese People′s Liberation Army from January 2015 to December 2023. The clinicopathological characteristics and immunohistochemical features were summarized using light microscopy. Two cases were tested for gene mutations by next-generation sequencing.Results:Of the 3 cases, 2 were male and 1 was female. The ages were 49, 61, and 53 years, respectively. Gross examination revealed that all tumors were single nodules with diameters of 7.0, 4.5, and 5.2 cm, respectively, grayish white in color with irregular borders. Cases 1 and 2 exhibited solid cut sections, whereas case 3 had cystic and solid cut sections. Microscopically, all cases had high WHO/ISUP nuclear grade (3 or 4) and overt invasion. Case 1 exhibited a solid, sheet-like growth pattern with numerous scattered glandular ducts or acinar structures. Case 2 displayed a diffusely growth pattern reminiscent of sarcoma. Case 3 demonstrated intracystic papillary and nodular infiltrative growth patterns. Large clear cytoplasmic vacuoles could be observed in the focal areas of case 1 and case 3. Prominent peritumoral lymphocytes in stroma were noted in case 1. Case 1 was diagnosed with regional lymph node metastasis, and case 2 was diagnosed with renal vein thrombosis. Immunohistochemical staining revealed that SDHB and SDHA were deficiently expressed in 3 cases, while PAX8, FH, and INI-1 exhibited diffuse expression. CD10 (1/3), CA9 (1/3), and CK20 (1/3) were occasionally expressed. The Ki-67 proliferation index ranged from 10% to 50%. Two cases underwent next-generation sequencing and were both found to harbor pathogenic mutations in SDHA (case 2 had a frameshift mutation, and case 3 had a splice site mutation). All 3 cases were followed up for 11 to 112 months. Case 2 died 11 months post-operation, while case 1 and case 3 survived for 19 and 112 months, respectively, without any recurrence or metastasis.Conclusions:High-grade SDH-RCC is a rare subtype of SDH-RCC. The tumor exhibits various architectural patterns and is often misdiagnosed as other types of renal cell carcinoma. The presence of cytoplasmic vacuoles may be indicative for diagnosis. Compared to typical SDH-RCC, the high-grade subtype generally shows a larger tumor size, higher TNM stage, greater invasive potential, and poorer prognosis. For high-grade SDH-RCC, routine SDHB immunohistochemical staining may be necessary. The occurrence of high-grade SDH-RCC may be associated with mutations in SDHA.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To investigate the efficacy and safety of conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery in the treatment of recurrent anterior shoulder dislocation(RASD)with scapula glenoid bone defect>15%and meshing Hill-Sachs lesion.Methods The clinical data of 65 patients with RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion admitted to our hospital from January 2022 to December 2024 were retrospectively analyzed.They were divided into group A,group B,and group C according to different surgical methods.Among them,group A underwent conventional open Latarjet surgery(n=18),group B underwent arthroscopic Latarjet surgery(n=21),and group C underwent arthroscopic Bankart repair combined with Remplissage surgery(n=26).The surgical conditions,preoperative and postoperative scores of related scales[visual analogue scale(VAS),Constant-Murley shoulder score,the University of California Los Angeles(UCLA)shoulder score],shoulder range of motion,postoperative complications and recurrence were compared among the three groups.Results Operation time:group B was longer than group A and group C(P<0.05),and group A was longer than group C(P<0.05).Intraoperative blood loss and hospital stay:group A was more or longer than group B and group C(P<0.05),group B was more or longer than group C(P<0.05).The VAS scores of the three groups at 1,6 and 12 months after operation were lower than those before operation(P<0.05).Pain VAS score at 1 and 6 months after operation:group A was higher than group B and group C(P<0.05).Pain VAS score at 1 month after operation:group B was higher than group C.Pain VAS score at 12 months after operation:there was no significant difference among the three groups(P>0.05).The UCLA shoulder scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).UCLA score at 1 month after operation:group A0.05).The Constant-Murley scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).Constant-Murley score at 1 month after operation:group A was lower than group B and group C(P<0.05).Constant-Murley score at 6 and 12 months after operation:three groups were equivalent(P>0.05).Forward flexion and lifting range of motion in the three groups:at 12 months after operation>before operation(P<0.05).Forward flexion and lifting range of motion was evaluated at 12 months after operation:there was no significant difference among the three groups(P>0.05).The range of motion of external rotation at body side and external rotation at 90° abduction before operation and at 12 months after operation:there was no significant difference between group A and group B(P>0.05).External rotation at body side and external rotation at 90° abduction of group C:at 12 months after operation of it was less than that before operation(P<0.05).The range of motion of external rotation at body side and external rotation at 90° abduction was obtained at 12 months after operation:group A and group B were greater than group C(P<0.05).Postoperative complication rate and recurrence rate:three groups were equivalent(P>0.05).Conclusion Conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery can effectively improve shoulder joint function and relieve pain in the treatment of RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion.However,the two shoulder arthroscopic procedures are less traumatic and have faster postoperative recovery.