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 observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

ObjectiveHyperlipidemia （HLP） is a chronic metabolic disease characterized by abnormal lipid metabolism and is one of the important risk factors for the occurrence of cardiovascular and cerebrovascular diseases. Its incidence has increased year by year， showing a trend toward younger onset. The overall prevalence of HLP among adults in China is as high as 40.40%. Although existing animal models provide important tools for research on the mechanisms of HLP， they generally show insufficient clinical concordance and lack the combined disease-syndrome characteristics of traditional Chinese medicine （TCM） and Western medicine. This article systematically reviews the research progress of HLP animal models， integrates the clinicopathological characteristics of TCM and Western medicine， and proposes new model construction strategies， aiming to provide an experimental basis for accurately analyzing the pathogenesis of HLP and developing integrated TCM-Western medicine therapies. MethodsBased on literature included in PubMed， CNKI， and Wanfang databases over the past 30 years， the construction methods and evaluation systems of HLP animal models were systematically retrieved and summarized. The concordance of existing animal models was calculated according to the new animal model evaluation method proposed by Professor MIAO Mingsan. ResultsAmong existing Western medicine modeling approaches， genetically modified models showed the highest concordance （72%）， followed by dietary induction （66%） and chemical drug induction （60%）. The dietary induction method is the most widely used in practice because of its simple operation and mature technology. Existing TCM modeling approaches are classified into three types， i.e.， spleen deficiency type， phlegm syndrome type， and liver-kidney yin deficiency type. Among them， the phlegm syndrome type shows a high degree of concordance. However， all three types have the problem of non-objective evaluation indicators and insufficient application of tongue and pulse assessment. ConclusionThe construction of existing HLP disease-syndrome combined animal models is still mainly based on Western medicine modeling methods and lacks adequate reflection of TCM syndromes. In the future， HLP animal models that conform to the clinical disease-syndrome characteristics of both TCM and Western medicine may be constructed through multifactor composite modeling strategies， intelligent tongue image analysis via robot learning， objective pulse detection， the establishment of objective evaluation systems for TCM syndromes through big data computing， and the application of cutting-edge technologies.

OBJECTIVE To explore the mechanism of Chaiqi yigan granules （CQYG） against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis； molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control （CON） group， CQYG drug-containing serum （CQYGKL） group， ferroptosis inducer （RSL3） group， mammalian target of rapamycin complex 1 （mTORC1） inhibitor （RMC-5552） group， mTORC1 agonist （CCT007093） group， and CCT007093+CQYGKL group. The levels of Fe 2+ ， malondialdehyde （MDA）， and glutathione （GSH） in the cells were detected in the former three groups； mRNA expressions of mammalian target of rapamycin （mTOR）， sterol regulatory element-binding protein 1 （SREBP1）， and stearoyl-CoA desaturase 1 （SCD1）， protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase （S6K） proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR， SREBP1， SCD1，etc. The main active components included quercetin， tanshinone Ⅱ A ， baicalein， etc. The binding energies of main active components to key targets were all less than －5 kJ/mol. Compared with CON group， the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased， while the levels of GSH were significantly decreased （ P ＜0.05）. mRNA expressions of mTOR， SREBP1 and SCD1， protein expressions of SREBP1 and SCD1， as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group， RSL3 group， and RMC-5552 group， whereas all the above indicators were significantly increased in the CCT007093 group （ P ＜0.05）. Compared with CCT007093 group， the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group （ P ＜0.05）. CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis， thereby exerting anti-liver cancer effects.

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.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

Objective:To observe any ability of pulsed electromagnetic field (PEMF) stimulation to regulate inflammation in degenerate nucleus pulposus cells.Methods:Primary nucleus pulposus cells from rats were cultured and divided into a control group, a model group, an A2AR-small interfering RNA group (A2AR-siRNA group), and a PEMF group. The control and model group cells were stimulated with tumor necrosis factor-α (TNF-α) in phosphate-buffered saline solution, those in the A2AR-siRNA and the PEMF groups were transfected with A2AR siRNA and given TNF-α stimulation. The PEMF group cells had four hours daily of PEMF irradiation beginning within 24 hours after the TNF-α stimulation for 2 days. After 48 hours, cell proliferation was detected by CCK8 assay, while the positive expression of A2AR in the nucleus pulposus cells was measured using immunofluorescence staining. The expression of A2AR, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element binding protein (CREB), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin-6 (IL-6) in the cells was observed using western blotting and real-time fluorescence quantitative polymerase chain reactions.Results:The rate of cell proliferation among the model group was approximately 60%, significantly lower than that of the control group (100%), but significantly higher than that of the A2AR-siRNA group (approximately 34%). The cell proliferation rate of the PEMF group was approximately 80%, significantly higher than that of the model and A2AR-siRNA groups. Compared with the control group, the positive expression of A2AR in the nucleus pulposus cells, A2AR protein and mRNA in the model group increased significantly in response to stress. The expression of A2AR protein and mRNA in the A2AR-siRNA group and the PEMF group was significantly lower than in the model group. Compared with the control group, the cAMP level in the nucleus pulposus cells of the model group had decreased significantly. The cAMP content in the A2AR-siRNA group further decreased compared with the model group, and that in the PEMF group increased compared with the model and the A2AR-siRNA groups. The average expression of PKA and CREB in the model group was significantly higher than among the control group, while that of PKA and CREB in the A2AR-siRNA group was significantly lower. The PKA and CREB protein levels in the PEMF group were slightly higher than in the A2AR-siRNA group, but the difference was not statistically significant. The expression of NF-κB, NLRP3, and IL-6 protein and mRNA in the cells of the model group was significantly higher than in the control group, but those of the A2AR-siRNA group were significantly higher than in the model group. The levels in the PEMF group were significantly lower than among the model and A2AR-siRNA groups, on average.Conclusions:Down-regulation of A2AR content further aggravates the inflammatory injury of degenerated nucleus pulposus cells. The mechanism may be related to the down-regulation of CREB activity, activation of the NF-κB signaling pathway, and subsequent up-regulation of inflammatory factors NLRP3 and IL-6. PEMF stimulation cannot significantly increase the A2AR level in degenerated nucleus pulposus cells, but it can promote the expression of cAMP and inhibit the downstream NF-κB signaling pathway, thereby exerting an anti-inflammatory effect.

Objective:To observe the clinical efficacy of different treatment methods in treating older patients with oral papilloma.Methods:A randomized controlled study was conducted on 40 older patients with oral papilloma who visited the Department of Stomatology of Beijing Hospital from August 2022 to November 2024.They were randomly divided into a surgical resection group and a 5-aminolevulinic acid (ALA) application group.There were 15 males and 25 females, with ages ranging from 60 to 82 (70.20 ± 6.53) years old.The ALA application group received ALA photodynamic therapy (PDT), while the surgical resection group underwent surgical resection of the papilloma.Visual analog scale (VAS) and self-assessment anxiety and depression scale were used to evaluate the two groups of patients at different periods.Results:All lesions in both groups achieved complete healing, with no recurrence observed during the 6-month follow-up period.Although the ALA application group received more treatment sessions than the surgical resection group, postoperative VAS scores and the duration of postoperative pain were both significantly lower [VAS score: (2.95±0.83) vs. (4.95±1.32) points; pain duration: (4.65±0.67) vs.(6.20±1.06) days]( t=5.755 and 5.540, respectively; both P<0.001). Before treatment, there was no statistically significant difference in either self- assessed anxiety or self- assessed depression scores between the two groups (both P>0.05). Six months after treatment, the self- assessed anxiety score in the ALA application group was significantly higher than that in the surgical resection group ( P<0.05), whereas no significant difference was observed in the self- assessed depression score ( P>0.05). Conclusions:Both ALA-PDT and surgical resection can effectively treat oral papilloma in older patients.However, ALA-PDT has lighter and shorter duration of postoperative pain, making it more suitable for treating lesions in special anatomical areas such as the corners of the mouth and the duct openings of the parotid glands.