Objective:To explore of auditory-vestibular function and inner ear imaging features of patients with Meniere's disease（MD） at different clinical stages. Methods:The clinical data of 110 patients with unilateral MD who were admitted from January 2023 to March 2024 were collected, and all patients were staged according to the results of pure tone hearing threshold test, including 13 patients with stage Ⅰ, 18 cases with stage Ⅱ, 65 cases with stage Ⅲ, and 14 cases with stage Ⅳ. All patients were tested for vestibular function, including caloric tests, vestibular evoked myogenic potentials（VEMPs）, vHIT and sensory integration tests（SOT）. The sites of endolymphatic hydrops were evaluated by intravenous endotogidolinium-based MRI, twenty-seven patients completed electrocochleography. Results:①The disease course time of patients with different stages was different, and the disease course time of stage Ⅰ and Ⅱ was shorter than that of stage Ⅲ and Ⅳpatients（P<0.05）. ②No statistical differences were found in clinical data or vestibular function between normal and abnormal ECochG groups（P>0.05）. ③The results of caloric tests showed that the UW% values of stage Ⅲ（45.5±14.79） and stage Ⅳ （51.57±22.44） were higher than those of stageⅠ（31.2±14.9） and stage Ⅱ（33.5±13.31）, there were statistically significant differences between stage Ⅰ and stage Ⅱ with stage Ⅲ and Ⅳ groups（P<0.05）, the total abnormal rate of cVEMP was 62.72%, there was a statistically significant difference between stageⅠand stage Ⅲ with the stage Ⅳ group（P<0.05）, the total abnormal rate of oVEMP was 71.82%, the difference between stage Ⅰ and stage Ⅳ group was statistically significant（P<0.05）. The total score of SOT comprehensive balance gradually decreased with the increase of clinical stage, and there was a significant difference between the stage Ⅰ and Ⅳ groups（H=26.08, P<0.01）, and there was a statistically significant difference in the rate of vestibular dysfunction of SOT between the two groups（χ²=6.7, P<0.05）. ④Patients with vestibular and cochlear endolymphatic hydrops, and patients with simple cochlear or vestibular had significantly differences in disease course time, clinical stages, UW% value of caloric test, abnormal rate of cVEMP and oVEMP, total SOT balance score, the rate of vestibular abnormality（P<0.01）. Among them, when the vestibular and cochlear endolymphatic hydrops are at the same time, the clinical stage of the patient is mainly stage Ⅲand Ⅳ. Conclusion:Auditory-vestibular and inner ear gadolinium-contrasted MRI examinations in clinical practice provide a supplementary reference for judging vestibular function and the type of endolymphatic hydrops.
Humans ; Meniere Disease/diagnostic imaging* ; Ear, Inner/physiopathology* ; Male ; Magnetic Resonance Imaging ; Female ; Middle Aged ; Vestibule, Labyrinth/diagnostic imaging* ; Adult ; Vestibular Evoked Myogenic Potentials ; Aged ; Audiometry, Pure-Tone ; Caloric Tests ; Vestibular Function Tests

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent

OBJECTIVES: This study aimed to investigate the correlation between clinical symptoms and unilateral chewing habits in patients with temporomandibular disorder (TMD) accompanied by tinnitus. METHODS: A total of 285 patients diagnosed with TMD at the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital between December 2020 and May 2024 were included and divided into two groups: tinnitus group and non-tinnitus group. Analysis was conducted on the proportion of patients with unilateral chewing habits in both groups, the correlation between the side of tinnitus and the side of unilateral chewing, and the correlation of tinnitus with TMD clinical symptoms (joint clicking, joint pain, and limited mouth opening) and unilateral chewing habits. The correlation of the type of disc displacement with unilateral chewing and tinnitus was also examined. RESULTS: In the tinnitus group, the proportions of patients with and without unilateral chewing habits were 90.70% (39/43) and 9.30% (4/43), respectively. In the non-tinnitus group, the proportions of patients with and without unilateral chewing habits were 76.03% (184/242) and 23.97% (58/242), respectively. The proportion of patients with unilateral chewing habits in the tinnitus group was significantly higher than in the non-tinnitus group (χ²=4.613, P<0.05). Correlation analysis showed a positive correlation between tinnitus and unilateral chewing habits (P<0.05). In the left-sided tinnitus group, the proportion of left-sided unilateral chewers [54.55% (12/22)] was higher than that of right-sided unilateral chewers [45.45% (10/22)]. In the right-sided tinnitus group, the proportion of right-sided unilateral chewers [81.82% (9/11)] was higher than that of left-sided unilateral chewers [18.18% (2/11)]. The difference was statistically significant (χ²=7.282, P<0.05). A positive correlation was also found between the side of tinnitus and the side of unilateral chewing habits (P<0.05). The proportion of patients with pain was significantly higher in the tinnitus group than in the non-tinnitus group (P<0.05). No significant difference in the proportion of joint clicking or limited mouth opening and disc displacement (no disc displacement, unilateral disc displacement, bilateral disc displacement, reducible disc displacement, or irreducible disc displacement) was found between the tinnitus and non-tinnitus groups (P>0.05). CONCLUSIONS TMD with unilateral chewing habits may be a contributing factor to unexplained tinnitus. Unexplained tinnitus is correlated with joint pain in patients with TMD.
Humans ; Tinnitus/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Mastication ; Male ; Adult ; Female ; Middle Aged ; Habits

Objective It aims to construct a quality evaluation index system for cancer multidisciplinary diagnosis and treatment(MDT)model in China from a full process perspective,providing guidance for practical application and model optimization.Methods Based on the number of MDT publications and practical situations,20 provincial-level hospitals nationwide were selected as typical cases.Rooted theory was used to extract evaluation indicators from the original text of the cases through three-level coding.A cancer MDT quality evaluation index system was constructed under the Input-Process-Output framework.Results Through three-level coding,27 initial categories,8 subcategories,and 3 main categories were sorted out,and a cancer MDT quality evaluation index system was constructed with input,process,and output as the primary evaluation indicators,and top-level design,management system,object resources,meeting preparation,meeting progress,plan implementation,patient outcomes,and hospital outcomes as the secondary evaluation indicators.Conclusion The quality evaluation index system of cancer MDT mode based on the perspective of the entire process can effectively guide practical optimization,but there is still a need for the improvement of supporting policies and information systems to assist in quality evaluation.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.

Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. Results All 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P<0.05). Statistically significant differences in p, q, and r subsets of round nodules were found in patients with pneumoconiosis at different stages (P<0.05). Observed nodule types included solid nodules, pure ground-glass shadow nodules, and partial solid nodules. There were statistically significant differences in pulmonary tuberculosis and bronchiectasis among different stages of coal workers' pneumoconiosis (P<0.05). There were statistically significant differences in interstitial shadows and patches combined with interstitial shadows among different stages of pneumoconiosis complicated with pneumonia (P<0.05). Conclusion MSCT provides images of the progression of coal workers' pneumoconiosis and have a certain relationship with the stages of coal workers' pneumoconiosis, which is conducive to the formulation of reasonable treatment plans in the early clinical stage. Therefore, in the diagnosis and treatment of pneumoconiosis, a great attention should be paid to the imaging technology of chest computerized tomography, especially the use of MSCT examination.