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.

ObjectiveTo characterize the features of the gut microbiome and its association with clinical prognosis in patients with intermediate and advanced hepatocellular carcinoma （HCC） treated with transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy. MethodsThis retrospective study enrolled patients with intermediate and advanced HCC who received TACE combined with targeted therapy and immunotherapy at the First Affiliated Hospital of Sun Yat-sen University from February 2025 to July 2025. Baseline clinical data and fecal samples were collected from all enrolled patients before the index hospitalization and treatment. Patients were stratified using two independent criteria： ① a good-prognosis group and a poor-prognosis group， based on whether progression-free survival （PFS） reached 6 months； ② a response group and a non-response group， based on tumor response to the first TACE assessed by the modified Response Evaluation Criteria in Solid Tumors （mRECIST）. Metagenomic sequencing was performed on fecal samples. Bioinformatic analysis was conducted to evaluate the diversity and compositional differences of intestinal bacterial and fungal communities between groups in each stratification， and to screen for prognosis-associated characteristic microbial taxa. ResultsA total of 61 patients met the inclusion criteria. Analysis of α-diversity and β-diversity showed no statistically significant differences in bacterial and fungal diversity between groups under either stratification strategy （P＞ 0.05）. At the bacterial level， Lactobacillus johnsonii （prognosis stratification： P=0.048； response stratification： P=0.043）， Bifidobacterium dentium （prognosis stratification： P=0.004； response stratification： P=0.030） and Clostridioides difficile （prognosis stratification： P=0.017； response stratification： P=0.016） were significantly enriched in both the good prognosis group and the response group. At the fungal level， Cryptococcus decaguttatus （P=0.045）， Puccinia striiformis （P=0.002）， and Kwoniella quercicola （P=0.015） were enriched in the good‑prognosis group； Kwoniella bestiolae （P=0.037） was enriched in the response group； and Akanthomyces muscarius （P=0.024） was enriched in the non-response group. Survival analysis based on the common differential bacterial abundance in both groupings showed a significant correlation between the abundance of Bifidobacterium dentium and patient prognosis. ConclusionDifferences in the gut microbiota are associated with the prognosis of patients with intermediate and advanced HCC treated with TACE combined with targeted therapy and immunotherapy. Bifidobacterium dentium may serve as a potential predictive biomarker for the efficacy of this combination regimen， and represents a potential intervention target to modulate treatment response. Differences in gut fungal communities are also potentially associated with the prognosis of intermediate and advanced HCC patients receiving TACE combined with targeted therapy and immunotherapy.

Background Patients with pneumoconiosis often have limited disease-related knowledge, insufficient access to health education, and substantial health management needs. Health education may help improve rehabilitation outcomes and quality of life in this population. Objective To evaluate the effects of health education based on the Listen-Establish-Adopt-Reinforce-Name-Strength (LEARNS) model on rehabilitation outcomes, health-related behaviors, and quality of life among pneumoconiosis patients, and provide effective intervention strategies for the rehabilitation management of patients with pneumoconiosis. Methods A randomized controlled trial was conducted. A total of 120 pneumoconiosis patients treated in the Department of Occupational Diseases, Beijing Emergency General Hospital, from November 2024 to February 2025 were enrolled. Participants were randomly assigned to a control group or an intervention group using a random number table method, with 60 patients in each group. The control group received routine pharmacotherapy, whereas the intervention group received a 12-week LEARNS model-based health-education intervention in addition to routine treatment. The 6-Minute Walk Test (6MWT) was used to assess exercise tolerance, and the modified Medical Research Council dyspnoea scale (mMRC) was used to evaluate dyspnoea. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were applied for psychological status assessment. Pulmonary function, including forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), was measured using spirometry. A self-designed scale was used to evaluate eight health-related behaviors targeted by the health education program. The 36-Item Short-Form Health Survey (SF-36) and Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) were used to assess quality of life, and the Pittsburgh Sleep Quality Index (PSQI) was adopted to evaluate sleep quality. Results After the 12-week intervention, the control group showed no statistically significant changes from baseline in the measured outcomes(P＞0.05). In the intervention group, exercise tolerance improved significantly, with the 6-minute walking distance increasing from (382.55±19.52) m to (426.84±33.59) m (P＜0.001). Dyspnoea was also alleviated, with the mMRC score decreasing from 1.37±0.66 to 0.96±0.54 (P＜0.001). The CAT score decreased from 18.95±7.03 to 10.67±3.64 (P＜0.001). Significant improvements were observed in anxiety and depression symptoms (P＜0.001), with the SAS score decreasing from 38.85±6.24 to 34.27±2.27, and the SDS score decreasing from 49.01±3.25 to 45.49±3.44. Sleep quality improved significantly, with the PSQI score dropping from 7.89±4.35 to 4.05±2.31 (P＜0.001). All eight health-related behaviors in the intervention group improved significantly after the intervention (P＜0.001), including acquisition of disease-related knowledge (1.87±0.34 vs. 3.13±0.45), participation in health education activities (1.89±0.52 vs. 3.61±0.38), and regular physical exercise (2.37±0.41 vs. 4.17±0.33). All SF-36 domain scores increased significantly (P＜0.05), with the most prominent improvements observed in physical functioning, general health, and vitality. At week 12, all SF-36 domain scores were significantly higher in the intervention group than in the control group (P＜0.05). No statistically significant between-group differences were detected in pulmonary function parameters (P＞0.05). Conclusion LEARNS model-based health education could improve exercise tolerance, dyspnea, psychological status, sleep quality, health-related behaviors, and quality of life among patients with pneumoconiosis, and therefore may be a useful adjunctive strategy for rehabilitation management in patients with pneumoconiosis.

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.

Objective:To develop a novel ovarian biological age prediction model based on DNA methylation for ovarian aging assessment.Methods:A prospective cohort study method was used. From March 2024 to January 2025, we collected 96 ovarian granulosa cell samples of infertility patients due to fallopian tube factors or male factors from the Reproductive Medicine Center of the Second Affiliated Hospital of Naval Medical University. Then we analyzed DNA methylation patterns across five age-associated gene regions ( ELOVL2, miR29B2C, TRIM59, KLF14 and FHL2) in a discovery cohort comprising 63 human ovarian granulosa cell samples. Targeted bisulfite sequencing was performed through PCR amplification followed by next-generation DNA sequencing. Leveraging elastic net regression analysis, we developed a predictive model incorporating 29 methylation sites that demonstrated strong age correlation. The model was subsequently validated using an independent cohort comprising 33 human ovarian granulosa cell samples. Results:The DNA methylation age prediction model based on ovarian granulosa cells showed the following results in the discovery cohort as follows: median absolute error (MAE) was 2.534 ( R=0.742, P<0.001). In the independent validation cohort, MAE was 3.019 ( R=0.729, P<0.001). Conclusion:In this study, we utilized human ovarian granulosa cells as experimental samples to develop a novel DNA methylation-based model for predicting ovarian biological age. By integrating multiple methylation sites across five age-related gene regions, this model serves as a robust indicator of ovarian aging status.

Objective To observe the clinical,CT and MRI manifestations of CIC-rear ranged sarcoma(CRS).Methods Eight patients with single CRS lesion ranged from 3.79 to 98.81 cm and the median of 21.37 cm were retrospectively enrolled,6 lesions located in deep soft tissue and 2 located in the femur.The clinical and imaging data were observed.Results All 8 CRS lesions presented as rapidly growing local masses,including 6 solid cystic soft tissue lesions and 2 non enlarged bone lesions with osteolytic bone destruction,which were all lobulated lesions with uneven equal-low density/slightly high T1 and slightly high T2 signals,with multiple focal map like necrosis.Diffusion weighted imaging showed lesions with limited diffusion and invasion of adjacent tissue,and"ice melting sign"was observed in 4 cases.After administration of contrast agents,the solid components of lesions enhanced unevenly and moderately or significantly and sustainedly,with slightly more pronounced enhancement at the edges,abundant blood vessels were visible inside and at the edges."Vascular floating sign"was noticed in 2 cases.Conclusion The clinical,CT and MRI manifestations of CRS had certain characteristics.

Subarachnoid hemorrhage(SAH)is a major subtype of stroke,characterized by high mortality and disability rates.Pyroptosis,a form of programmed cell death,has been identified as a key pathological process in early brain injury.Current research indicates that pyroptosis can occur in neurons,microglia,astrocytes,and cerebral vascular endothelial cells after SAH,leading to neurological dysfunction,brain edema,and disruption of the blood-brain barrier.The NOD-like receptor protein 3(NLRP3)inflammasome is regarded as a central regulatory component of pyroptosis,and its activation mechanisms and roles in various cell types have become focal points of research.A variety of therapeutic strategies targeting this pathway have emerged,including NLRP3 inhibitors,Caspase-1 inhibitors,and Gasdermin-D inhibitors.The aforemenetioned approaches all have demonstrated efficacy in animal studies.Additionally,novel technologies such as stem cell therapy,exosome therapy,and gas therapy offer novel intervention approaches for modulating pyroptosis.Although,various therapeutic strategies targeting pyroptosis-related pathways have emerged in recent years,a comprehensive summary remains absent.This article reviewed the advancements in pyroptosis research following SAH and associated treatment strategies,aiming to provide a theoretical foundation for subsequent mechanistic studies and clinical translation.

Objective:To analyze the burden and trends of noncommunicable chronic disease(NCD) attributable to metabolic factors in China from 1990 to 2021.Methods:Data from the Global Burden of Diseases(GBD) 2021 database were utilized to describe changes in mortality and disability-adjusted life years(DALYs) of NCD in China from 1990 to 2021. Stratified analyses were conducted by age, sex, sociodemographic index(SDI), and related risk factors. Statistical analyses and predictions were conducted using the age-period-cohort model and the Nordpred model.Results:In 2021, the age-standardized mortality rate and age-standardized DALYs rate of NCD attributable to metabolic factors in China were 227.56 per 100 000 and 4 829.39 per 100 000, respectively. Their average annual percentage changes were -0.76%( P<0.001) and -0.77%( P<0.001). Overall, the burden decreased progressively with higher SDI levels. Analysis using the age-period-cohort model indicated reduced birth cohort and period effects for metabolic factor-attributable NCD, while age effects rose significantly. The minimum relative risk( RR) value was observed in the 15-19 age group( RR=0.01), and the maximum RR value occurred in the 95-99 age group( RR=996.86). The overall rising mortality trend indicated that age effects are the predominant driver at present. Projections estimate that by 2046, deaths from metabolic factor-attributable NCD in China will reach 8 189 563, with an age-standardized mortality rate of 236.95 per 100 000. Conclusions:China continues to face a substantial burden of NCD linked to metabolic factors, with older adults, males, and individuals with hypertension, diabetes, and prediabetes identified as key populations requiring targeted interventions.

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.