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.

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 effects of Zhuang medicinal thread moxibustion on apoptosis of interstitial cells of Cajal(ICC)in gastric smooth muscle of diabetic gastroparesis(DGP)rats via regulation of the p38MAPK signaling pathway.Methods Totally 60 rats were randomly divided into a blank group(10 rats)and a modeling group(50 rats).DGP models were established in the modeling group via intraperitoneal injection of streptozotocin.50 successfully modeled rats were further randomized into model group,Western medication group,prevention+treatment group,prevention group and treatment group,with 10 rats in each group.The Western medication group was administered mosapride citrate by gavage for 3 weeks starting at week 10;the prevention+treatment group underwent Zhuang medicinal thread moxibustion("Zhongwan",bilateral"Neiguan"and"Zusanli")intervention for 6 weeks starting at week 7;the prevention group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 7;and the treatment group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 10,3 cones per point,once a day;the blank group and model group received handling only.The random blood glucose and body mass of rats were detected,and the gastric emptying rate and intestinal propulsion rate were calculated.HE staining was used to observe the morphology of gastric smooth muscle tissue,TUNEL staining was used to detect the apoptosis of gastric smooth muscle tissue,ELISA was used to detect the contents of Caspase-3,TNF-α,IL-1β and IL-6 in gastric smooth muscle tissue,immunohistochemistry was used to detect the positive expressions of Cx43 and c-kit in gastric smooth muscle tissue,Western blot was used to detect the expressions of p38MAPK,p-p38MAPK,BAX and Bcl-2 protein in gastric smooth muscle tissue.Results Compared with the blank group,the random blood glucose significantly increased in the model group(P<0.01),and the body mass,gastric emptying rate and small intestinal propulsion rate significantly decreased(P<0.01),the blood vessels of gastric tissue were not clear,the surface was not smooth,the mucosal folds were less,the arrangement of gastric smooth muscle cells was disordered,the nuclear membrane was not clear,and there were vacuole like changes between cells,the apoptosis rate significantly increased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the protein expressions of p38MAPK,p-p38MAPK and BAX in gastric smooth muscle tissue significantly increased(P<0.01),and the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio significantly decreased(P<0.01).Compared with the model group,the random blood glucose of rats in each intervention group decreased,and the body mass,gastric emptying rate and intestinal propulsion rate increased(P<0.01),the blood vessels of gastric tissue were clear,the inner surface of stomach was smooth,the mucosal folds were not rich,no ulcer was found,the shape of gastric smooth muscle cells was complete,the nuclear membrane was clear,and the arrangement of muscle cells was regular,the apoptosis rate significantly decreased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the expressions of p38MAPK,p-p38MAPK,BAX protein in gastric smooth muscle tissue decreased(P<0.05,P<0.01),the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio increased(P<0.05,P<0.01).The overall effect of the prevention+treatment group was better than that of the Western medication group,prevention group and treatment group(P<0.05,P<0.01).Conclusion Zhuang medicinal thread moxibustion may reduce gastric inflammation and ICC apoptosis in DGP rats by inhibiting p38MAPK signaling pathway,so as to improve DGP gastric motility disorder,and the effect of early intervention is more significant.

Objective:To investigate the clinicopathological characteristics of well-differentiated papillary mesothelial tumor (WDPMT).Methods:Sixteen cases of resected WDPMTs diagnosed at the Affiliated Hospital of Qingdao University, Qingdao, China from 2017 to 2024 were collected and the clinicopathological features were retrospectively analyzed.Results:There were 7 males amd 9 females, with a mean age of 53.8±14.8 years (range, 25-83 years). Tumor size ranged from 3 to 12 mm in maximum diameter. Of the 16 cases, 15 involved the peritoneum and 1 involved the pleura, one of which occurred on the surface of ovary. All cases were incidentally identified during unrelated surgical procedures. Histologically, tumors exhibited arborizing papillary growth patterns and frequently displayed hierarchically branching papilla. Tumor cells showed cuboidal to flattened cell morphology with minimal nuclear atypia. Mitotic figures were not noted in all cases. Entrapped gland-like tumor cell clusters were found in the stroma of tumor papilla in 1 of the 16 cases. Immunohistochemically, the tumor cells expressed mesothelial markers (Calretinin, D2-40, and CK5/6) in all cases, and BAP1 and MTAP were immunoreactive in all tested cases. Fluorescence in situ hybridization revealed no CDKN2A deletions.Conclusions:WDPMT predominantly occurs in the peritoneum and typically demonstrates indolent biological behaviors. It often shows overlapping features with mesothelioma in situ and epithelioid mesothelioma. The hierarchical branching papillae is its diagnostic hallmark, while routine immunohistochemical evaluation of BAP1 and MTAP is also recommended for differential diagnosis of these tumors.

Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

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.