OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

With the emergence of unhealthy dietary structures in people’s life， metabolic associated fatty liver disease （MAFLD） has gradually become the most important chronic liver disease in China， and there is also a gradual increase in the cases of MAFLD-associated liver cancer. Adipose tissue not only has the function of energy storage， but also secretes adipokines that play an important role in the development and progression of MAFLD and its associated liver cancer. Studies on the mechanism of adipokines have provided important help for the prevention and treatment of MAFLD， and a large number of studies have shown that the abnormal secretion of adipokines is associated with MAFLD and plays an important regulatory role in the development and progression of liver cancer. Adipokines are not only regulated at the gene level， but they can also interact with genes through specific pathways to co-regulate pathophysiological processes such as inflammation， metabolism， immunity， and cell proliferation in MAFLD and its associated liver cancer. This article reviews the latest studies on the association of adipokines with MAFLD and its associated liver cancer， in order to provide new directions for further research on the pathogenesis of liver cancer.

Aortic dissection is a life-threatening cardiovascular disease with devastating complications and high mortality. It requires rapid and accurate diagnosis and a focus on prognosis. Many laboratory tests are routinely performed in patients with aortic dissection including D-dimer, brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin. D-dimer shows vital performance in the diagnosis of aortic dissection, and brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin exhibits important value in risk stratification and prognostic effect in aortic dissection patients. Our review summarized the clinical utility of these laboratory tests in patients with aortic dissection, aiming to provide advanced and comprehensive evidence for clinicians to better understand these laboratory tests and help their clinical practice.

Objective To propose an innovative self-supervised learning method for vascular segmentation in computed tomography angiography (CTA) images by integrating feature reconstruction with masked autoencoding. Methods A 3D masked autoencoder-based framework was developed, where in 3D histogram of oriented gradients (HOG) was utilized for multi-scale vascular feature extraction. During pre-training, random masking was applied to local patches of CTA images, and the model was trained to jointly reconstruct original voxels and HOG features of masked regions. The pre-trained model was further fine-tuned on two annotated datasets for clinical-level vessel segmentation. Results Evaluated on two independent datasets (30 labeled CTA images each), our method achieved superior segmentation accuracy to the supervised neural network U-Net (nnU-Net) baseline, with Dice similarity coefficients of 91.2% vs. 89.7% (aorta) and 84.8% vs. 83.2% (coronary arteries). Conclusion The proposed self-supervised model significantly reduces manual annotation costs without compromising segmentation precision, showing substantial potential for enhancing clinical workflows in vascular disease management.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

OBJECTIVE: To identify the risk factors associated with the development of post-Nuss procedure scoliosis in pectus excavatum patients and to establish a relevant predictive model. METHODS: A retro-spective review was conducted on pectus excavatum patients who underwent Nuss procedure in Department of Thoracic Surgery at Beijing Jishuitan Hospital between January 2018 and February 2023. We gathered the patient demographic information (including age, sex, height, weight, and body mass index) and diagnostic imaging results (echocardiogram, chest CT scan, full-spine radiography, and PA/lateral chest X-rays), and measurements of Haller index, asymmetry index, sternal torsion angle (STA) index, and Cobb angle changes. The risk of post-Nuss procedure scoliosis was assessed. Cox regression analysis was performed to identify independent risk factors for scoliosis development in the pectus excavatum patients. Based on the results of the Cox regression analysis, a risk prediction model was established, and its specific predictive performance was assessed through internal cross-validation. RESULTS: A total of 59 pectus excavatum patients who underwent Nuss procedure were included after applying inclusion and exclusion criteria. The median follow-up duration was 6.84 months, and the follow-up results showed significant improvements in Haller index, STA index, and asymmetry index postoperatively. Twelve patients developed scoliosis 3 months after Nuss procedure, while 47 patients did not, the incidence of scoliosis was 20.3%. Cox regression analysis identified preoperative pulmonary artery hypertension and preoperative asymmetry index as independent risk factors for post-Nuss procedure scoliosis. A predictive model was constructed based on single-factor Cox regression analysis results, incorporating age, height, weight, body mass index, preoperative pulmonary artery hypertension, preoperative Haller index, STA index, asymmetry index, and Cobb angle. The receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) for the overall predictive model was calculated to be 0.995. A calibration curve demonstrated good alignment between predicted values and actual values. CONCLUSION Nuss procedure achieved favorable clinical outcomes. However, postoperative scoliosis emerged as a significant complication with a high incidence rate. Pulmonary artery hypertension and asymmetry index were independent predictors of post-Nuss procedure scoliosis. The predictive model developed in this study demonstrated robust performance in estimating the risk of postoperative scoliosis.
Humans ; Funnel Chest/surgery* ; Scoliosis/etiology* ; Child ; Male ; Female ; Adolescent ; Risk Factors ; Young Adult ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Proportional Hazards Models

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.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

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.