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 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.

OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）. METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （ P ＜0.05）. The expression level of E-cadherin protein was significantly increased （ P ＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （ P ＞0.05）. CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

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.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

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

Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.

Objective To explore the potential categories of dyadic psychological capital and related factors among stroke patients and their spouses,in order to inform the improvement of their mental health.Methods Stroke patients and their spouses were recruited in the Neurology Department of 3 tertiary general hospitals from March,2023 to August,2023 by convenience sampling method.The general information questionnaire,Modified Rankin Scale(mRs),Psychological Capital Questionnaire,The Kessler Psychological Distress Scale(K10)and Perceived Social Support Scale(PSSS)were used for investigation.Latent profile analysis was adopted to explore the categories of dyadic psychological capital,and multiple Logistic regression analysis was used to assess the effect of various factors on different categories.Results A total of 232 returned questionnaires(out of the 235)were valid,resulting an effective response rate of 98.7％.Stroke patients and their spouses were divided into 3 categories,including dyadic low psychological capital-low self-efficacy group(6.0％),dyadic high psychological capital-low resilience group(15.9％)and dyadic medium psychological capital group(78.1％).The stroke patients'education level,mRs scores,occupational status after the illness,level of perceived social support,and spouses'working condition were the influencing factors on potential profiles of dyadic psychological capital(P＜0.05).Conclusion There are heterogeneity and interdependence in the level of dyadic psychological capital of stroke patients and their spouses.Healthcare professionals should promote dyadic mental health by developing targeted interventions for stroke patients and their spouses with different psychological capital characteristics from a dyadic holistic perspective.

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.