1.Mechanism of KLF4 in regulating ferroptosis in diabetic nephropathy
Huanzhen ZHANG ; Zhangyong DAN ; Xiaorui SHI ; Rumeng ZHU ; Yi WANG ; Huaqing ZHU
Acta Universitatis Medicinalis Anhui 2026;61(3):509-517
ObjectiveTo investigate the role of Krüppel-like factor 4 (KLF4) in type 1 diabetic nephropathy (DN) and to elucidate its underlying mechanisms. MethodsSixteen male Sprague-Dawley (SD) rats were selected and randomly divided into control group and model group, with 8 rats in each group. Rats in model group were intraperitoneally injected with a single dose of 55 mg/kg streptozotocin (STZ) to establish a diabetic nephropathy (DN) model, while those in control group were injected with an equal volume of sodium citrate buffer at the same time. After successful model establishment, the serum levels of blood urea nitrogen (BUN) and serum creatinine (SCR) were determined. Hematoxylin-eosin (HE) staining was performed on renal tissues to observe pathological changes, and immunofluorescence staining was conducted to detect the expression of KLF4 in renal tissues. Lipid peroxidation levels were evaluated by measuring malondialdehyde (MDA), Fe²⁺, and lipid peroxidation products in rat kidneys. A high glucose (HG)-induced cell injury model was established in HK-2 cells, with mitochondrial membrane potential assessed using 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. Lipid peroxidation levels (MDA, Fe²⁺, and lipid peroxides) were measured in HK-2 cells.KLF4-overexpressing HK-2 cells were then constructed, followed by repeated JC-1, MDA, Fe²⁺, and lipid peroxidation assays. Western blot was performed to evaluate the expression of ferroptosis-related proteins including glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (NRF2), and Kelch-like ECH-associated protein 1 (Keap1), in renal tissues, HK-2 cells, and KLF4-overexpressing HK-2 cells. ResultsCompared with the control group, DN rats exhibited elevated serum BUN and SCR levels, glomerular hypertrophy, renal interstitial fibrosis, and decreased KLF4 expression. Additionally, MDA, Fe²⁺, and lipid peroxidation levels increased, indicating enhanced ferroptosis in renal tissues, accompanied by reduced GPX4 and NRF2 expression and elevated Keap1 levels. Similarly, HG-treated HK-2 cells showed decreased KLF4 expression, increased MDA, Fe²⁺ and lipid peroxidation, elevated ferroptosis, and dysregulated GPX4/NRF2/Keap1 expression. However, KLF4 overexpression reversed these alterations induced by high glucose treatment. ConclusionIn the renal tissues of type 1 diabetic rats, the expression of KLF4 decreases the level of ferroptosis increases, and KLF4 overexpression could alleviate HG-induced HK-2 cell injury.
2.Adhesion Mechanisms of Aquatic Fouling Organisms Mediated by Biomacromolecules
Dan HE ; Shi-Guo LI ; Ai-Bin ZHAN
Progress in Biochemistry and Biophysics 2025;52(7):1833-1852
Aquatic organisms can secrete biomacromolecules through specialized organs, tissues, or structures, enabling adhesion to underwater material surfaces and leading to severe biofouling issues. This phenomenon adversely impacts aquatic ecosystem health and human activities. Biofouling has emerged as an emerging global environmental challenge. Adhesion serves as the foundation of biofouling, representing a critical step toward a comprehensive understanding of the adhesion mechanisms of aquatic organisms. Biomacromolecules, including proteins, lipids, and carbohydrates, are the primary functional components in the adhesive substances of aquatic fouling organisms. Research indicates that these biomacromolecules exhibit diversity in types and characteristics across different aquatic organisms, yet their adhesion mechanisms show unifying features. Despite significant progress, there remains a lack of comprehensive reviews on the adhesion mechanisms mediated by biomacromolecules in aquatic fouling organisms, particularly on the roles of lipids and carbohydrates. Through a comprehensive analysis of existing literature, this review systematically summarizes the mechanistic roles of three classes of macromolecules in aquatic biofouling adhesion processes. Proteins demonstrate central functionality in interfacial adhesion and cohesion through specialized functional amino acids, conserved structural domains, and post-translational modifications. Lipids enhance structural stability via hydrophobic barrier formation and antioxidative protection mechanisms. Carbohydrates contribute to adhesion persistence through cohesive reinforcement and enzymatic resistance of adhesive matrices. Building upon these mechanisms, this review proposes four prospective research directions: optimization of protein-mediated adhesion functionality, elucidation of lipid participation in adhesion dynamics, systematic characterization of carbohydrate adhesion modalities, and investigation of macromolecular synergy in composite adhesive systems. The synthesized knowledge provides critical insights into underwater adhesion mechanisms of aquatic fouling organisms and establishes a theoretical foundation for developing mechanism-driven antifouling strategies. This work advances fundamental understanding of bioadhesion phenomena while offering practical guidance for next-generation antifouling technology development.
3.Relationship among occupational stress, work-related rumination, and sleep quality in emergency medical dispatchers in some areas of China
Xiaoying SHI ; Qing ZHANG ; Zhongyuan YAN ; Qin ZHANG ; Dan XU
Journal of Environmental and Occupational Medicine 2025;42(8):932-938
Background The increasing demand for emergency services coupled with the special working environment has exacerbated occupational stress and work-related rumination among emergency medical dispatchers, which is noteworthy for its impact on dispatchers' sleep quality. Objective To explore the relationship among occupational stress, work-related rumination, and sleep quality of emergency medical dispatchers, so as to provide reference for improving sleep quality and maintaining physical and mental health of this occupational group. Methods A total of 386 emergency medical dispatchers from 16 provinces and municipalities including Beijing, Shanghai, Tianjin, Inner Mongolia, Zhejiang, Shanxi, Jiangxi, Anhui, Hubei, Hebei, Henan, Sichuan, Guizhou, Yunnan, Fujian, and Hainan of China were investigated with the Chinese version of Effort-Reward Imbalance Questionnaire, Work-Related Rumination Questionnaire, and Insomnia Severity Index. Spearman correlation was used to analyze the association among occupational stress, work-related rumination, and sleep quality. A structural equation model was constructed, with occupational stress as independent variable, the two dimensions of work-related rumination as mediating variables, and sleep quality as dependent variable, respectively. Bootstrap testing was then used to verify potential mediating effect of work-related rumination on the relationship between occupational stress and sleep quality among the emergency medical dispatchers. Results Among the enrolled emergency medical dispatchers, the effort-reward imbalance (ERI) index was 1.03, the score of affective rumination was 15.35±5.26, the score of problem-solving rumination was 17.64±4.63, and the total score of sleep quality was 21.10±6.53. Their ERI index was positively correlated with affective rumination scores (r=0.636, P<0.01), but not with problem-solving rumination scores (P>0.05). Their ERI index, affective rumination scores, and problem-solving rumination scores were positively correlated with sleep quality scores (P<0.05). The direct effect size of occupational stress on sleep quality was 0.627, the indirect effect size of affective rumination was 0.124, and the mediating effect of affective rumination accounted for 16.4% of the total effect (0.755), while the problem-solving rumination had no mediating effect on the relationship between occupational stress and sleep quality. Conclusion Occupational stress and affective rumination in emergency medical dispatchers can predict their sleep quality. Occupational stress can directly affect sleep quality, and indirectly affect it through affective rumination. Managers should pay attention to and evaluate the affective rumination level of emergency medical dispatchers, so as to take corresponding intervention measures to reduce their occupational stress and improve their sleep quality.
4.Risk factors for cough variant asthma and its relationship with changes in indoor environment
Jieyu SHI ; Dan ZHOU ; Mengtan LIU
Journal of Public Health and Preventive Medicine 2025;36(5):145-148
Objective To analyze the risk factors for cough variant asthma (CVA) and investigate the influence of indoor environment on CVA. Methods From July 2021 to August 2024, 315 patients admitted to the hospital due to CVA were selected as the CAV group. Meanwhile, 100 healthy individuals were selected as the control group. Clinical data of all subjects were collected. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of CVA. Results The proportions of subjects with family history and recurrent respiratory tract infection in the CVA group were higher than those in the control group (P<0.05). The CVA group had significantly higher rates of indoor renovation, mold growth, infrequent bedding cleaning, opening window for ventilation once to 3 times a week, keeping pets, and passive smoking compared to the control group within one year, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis results showed that indoor-decoration in the past year (OR=2.282, 95%CI: 1.1454.549), mould growth (OR=2.036, 95%CI: 1.228-3.376), opening window for ventilation once to 3 times a week (OR=1.895, 95%CI: 1.253-2.865), seldom cleaning bedding (OR=2.257, 95%CI: 1.132-4.499), keeping pets (OR=2.071, 95%CI: 1.146-3.743), and passive smoking (OR=2.208, 95%CI: 1.377-3.541) were independent risk factors for CVA (P<0.05). Conclusion There is a significant correlation between the occurrence of CVA and indoor environment. Changes in indoor environment include indoor-decoration in the past year, mould growth, low frequency of opening window for ventilation, low frequency of bedding cleaning, keeping pets and passive smoking which are risk factors for the occurrence of CVA.
5.Performance comparison of domestic and imported CD3/CD28 activation beads for CAR-T cell manufacturing
Xianzheng WEI ; Shuyu ZHANG ; Yuhang JIN ; Pu WANG ; Xu WANG ; Junnian ZHENG ; Dan LIU ; Ming SHI
Chinese Journal of Cancer Biotherapy 2025;32(5):492-497
Objective:To compare the performance differences of domestic and imported CD3/CD28 activation beads for manufacturing CAR-T cells,providing a backup or alternative for domestic CAR-T cell research and manufacture.Methods:A mature protocol using imported CD3/CD28 activation beads with a 1∶1 ratio for CD3+T cells was implemented as research control.Domestic beads were used with gradient ratios of 1∶2,1∶1,and 2∶1 to activate T cells.72 h after T cell activation,CAR-T cells were manufactured by CAR lentiviral infection and cell proliferation was monitored at 2-,4-,and 7-days post-infection.Flow Cytometry was used to detect CAR-T cell positivity 5 days after infection and to detectCD4/CD8 phenotype of CAR-T cells and PD1+TIM3+cell exhaustion ratio 8 days after infection.Results:CAR-T cells manufactured by domestic CD3/CD28 activation beads exhibited similar phenotype compared with those manufactured by imported CD4/CD8 beads.The positive rate of CAR-T cells prepared with domestic beads was slightly lower than that of imported beads(53.7%vs 57.9%).However,the proliferation of CAR-T cells manufactured by domestic beads was about twice that of cells manufactured by imported beads,and the exhaustion level was only half that of imported beads(4.21%vs 7.91%).Moreover,the use of domestic magnetic beads was lower than that of imported magnetic beads,which was advantageous for cutting the costs of CAR-T cells research and manufacture.Conclusion:Domestic CD3/CD28 activation beads used for CAR-T cells manufacturing demonstrate comparable overall performance to their imported counterparts,showing potential as a backup or alternative for imported beads.
6.Application of cymene care solution in prognostic management of chronic periodontitis
Bing HAN ; Dan WANG ; Hao GUO ; Tong ZUO ; Ya'nan SHI ; Juan TONG ; Huan ZHANG ; Rui LIU
Journal of Practical Stomatology 2025;41(3):417-419
40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P<0.05)and the rate of probing bleeding sites(P<0.05)more effectively,and showed no statistical significance in the change of attachment loss(P<0.05).Cymene care solution is effective in the improvement of periodontal health.
7.Study on mechanism of Wenshen Jianpi recipe regulating autophagy by p70S6K signaling pathway on alleviating podocyte injury in diabetic nephropathy rats
Bo SHI ; Ru-yao LI ; Ting-long JIN ; Jin WANG ; Xiao-dan CAO
Chinese Pharmacological Bulletin 2025;41(3):567-573
Aim To detect the mechanism of Wenshen Jianpi recipe(WSJPR)regulating the autophagy by p70S6K signaling pathway on alleviating podocyte inju-ry in diabetic nephropathy(DN)rats.Methods DN model rats induced by streptozotocin were divided into five groups with six rats in each group:model control group,low dose group(7.5 g·kg-1·d-1),medium dose group(15 g·kg-1·d-1),high dose group(30 g·kg-1·d-1),and positive control group(25 mg·kg-1·d-1).In addition,six normal rats were used as negative control group(isotonic NaCl solution 10 mL·kg-1·d-1).All the rats were given continuous ga-vage for eight weeks.Fasting blood glucose,urine al-bumin/creatinine ratio(UACR)and blood viscosity were determined.The changes of podocyte ultrastruc-ture and autophagosome in each group were observed by transmission electron microscopy(TEM).The pro-tein levels of signaling pathway factor p70S6K and au-tophagy factor p62 in renal tissues of rats in each group were detected by Western blot.Besides,p62 expres-sion was observed by immunohistochemistry.Results WSJPR could decrease fasting blood glucose and UACR,and improve the indexes of blood viscosity in rats.TEM indicated that WSJPR could significantly improve the podocyte ultrastructure and autophagy level in DN rats.Western blot showed that the expression level of signaling pathway factor p70S6K and autophagy factor p62 in the kidney of DN rats increased signifi-cantly compared with blank control group(P<0.01).The expression level of p70S6K and p62 in WSJPR groups decreased compared with model control group(P<0.05).Among them,the medium-dose group of WSJPR had the most significant change.Immunohisto-chemical results showed that the level of autophagy fac-tor p62 in kidney tissue of DN rats increased compared with the control group.WSJPR had a certain inhibitory effect on p62 expression in DN rats.Conclusion WSJPR might restore cell homeostasis by inhibiting p70S6K level,reducing the expression of autophagy factor p62 and enhancing autophagy level in renal tis-sue of DN rats.
8.Effects of GGH genetic polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate in children with intracranial tumors
Dan-qi ZHAO ; Zheng-yuan SHI ; Xi-qiao XU ; Shu-mei WANG
The Chinese Journal of Clinical Pharmacology 2025;41(2):183-187
Objective To investigate the effects of γ-glutamyl hydrolase(GGH)rs11545078 C>T polymorphisms on serum concentrations,chemotherapy toxicities of methotrexate(MTX),and prognosis in children with intracranial tumors.Methods Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA.Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C>T polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of toxicities,relapse,and metastasis were recorded after chemotherapy with MTX.The associations of GGH rs11545078 C>T polymorphisms with concentration-to-dose ratios(C/D ratios),chemotherapy toxicities of MTX,relapse,and metastasis of tumors were analyzed.Results A total of 75 children were included in the present study.The frequencies of rs11545078 CC and CT genotypes were 82.67%and 17.33%,respectively.The frequencies of C and T alleles were 91.33%and 8.67%,respectively.There were no statistically significant differences for these frequencies among the children with intracranial tumors,the children with acute lymphoblastic leukemia,and the health population in Beijing.Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h(25.19 and 0.14 μmol·L-1 per g·m-2,respectively),higher metastasis rates(46.77%),and lower relapse rates(17.74%)than those in CT genotype carriers(22.01 and 0.11 μmol·L-1 per g·m-2,38.46%,and 30.77%,respectively),and the differences were no statistically significant(all P>0.05).The incidences of gastrointestinal disorders(76.92%)in children with the CT genotype were significantly higher than those in CC genotype carriers(45.16%,P<0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype(all P>0.05).Conclusion GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.
9.Efficacy of CT-based interpretable integrated learning model for differentiating lung squamous cell carcinoma and adenocarcinoma
Shi-ze QIN ; Xiu-fu ZHANG ; Xue ZHOU ; Dan SU ; Yong-ying LIU ; Fang WANG ; Qing JIA
Chinese Medical Equipment Journal 2025;46(7):12-20
Objective To investigate the efficacy of an interpretable integrated learning model combining clinical indicators,CT image features and radiomics features for the differential diagnosis of lung squamous cell carcinoma and adenocarcinoma,so as to provide references for clincal treatment decisions.Methods A retrospective analysis was conducted on clinical and imaging data from 220 patients(231 lesions)with primary non-small cell lung cancer at Jiangjin Central Hospital of Chongqing(Center 1)and 83 patients(84 lesions)at Chongqing General Hospital(Center 2).In Center 1,the squamous cell carcinoma group consisted of 60 patients(60 lesions),while the adenocarcinoma group included 160 patients(171 lesions).In Center 2,the squamous cell carcinoma group comprised 18 patients(18 lesions),and the adenocarcinoma group involved 65 patients(66 lesions).The patients were categorized into squamous cell carcinoma and adenocarcinoma groups based on pathological findings.Center 1 was randomly partitioned into a training set and a validation set at a 7∶3 ratio,while Center 2 served as the independent test set.Firstly,a deep learning model,VB-Net,was used to automatically segment the tumor region on the lung window image;secondly,the SMOTE(synthetic minority oversampling technique)method was used to balance the categories in the training set and standardize the extracted features with Z-scores;thirdly,the least absolute shrinkage and selection operator(LASSO)were used to select the optimal radiomics features and calculate the radiomics score(Radscore),and univariate and multivariate logistic regression was used to screen clinical indicators and independent clinical factors for differentiating lung squamous cell carcinoma and adenocarcinoma in CT image features;finally,three ensemble learning algorithms(AdaBoost,Bagging decision tree and XGBoost)were used to combine independent clinical factors and Radscore to construct the model.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of the models.SHAP technique was used to analyze the feature contribution and model decision-making process.Results Among the evaluated ensemble models,AdaBoost and Bagging decision trees demonstrated overfitting tendencies.In contrast,the XGBoost model showed the best performance,achieving AUC values of 0.939,0.887 and 0.853 in the training,validation and independent test sets,respectively.SHAP indicated that Radscore was the most important feature affecting the performance of the model.The decision diagram enabled the visualization of the diagnostic process of the model.Conclusion The interpretable integrated learning model based on clinical indicators,CT image and radiomics features is expected to non-invasively diagnose lung squamous cell carcinoma and adenocarcinoma before treatment and assist clinicians make treatment decisions as early as possible.[Chinese Medical Equipment Journal,2025,46(7):12-20]
10.Hemodynamic characteristics during the initial phase of head-up tilt test in children with postural orthostatic tachycardia syndrome and the value for predicting vasovagal syncope
Dan ZHANG ; Yao LIN ; Yanyan LIU ; Yang LIU ; Lin SHI
Chinese Pediatric Emergency Medicine 2025;32(9):656-662
Objective:To analyze hemodynamic characteristics during the initial phase of the head-up tilt test (HUTT) in children with postural orthostatic tachycardia syndrome (POTS) and the value for predicting vasovagal syncope(VVS).Methods:This was a case-control study involving 123 POTS patients who underwent HUTT in the Pediatric Cardiovascular Department at the Children's Hospital,Capital Institute of Pediatrics,from January 2021 to August 2023.According to HUTT results,participants were divided into POTS combined with VVS group( n=82) and POTS group( n=41).The general conditions,clinical symptoms,24-hour urine sodium levels,and hemodynamics changes during the initial phase of HUTT between the two groups were compared. Results:The prevalence of POTS combined with VVS was 66.13% (82/123).There were no significant differences in age,sex,body mass index,24-hour urinary sodium,heart rate,heart rate variability,and maximum heart rate variability during the initial phase of HUTT between the two groups( P>0.05).Compared to the POTS group,the 10-minute systolic blood pressure(SBP10),10-minute diastolic blood pressure (DBP10),and 10-minute mean blood pressure(MBP10) in the POTS combined with VVS group were significantly lower [SBP10: 104(98.8,114.3) vs. 111(105,121.5)mmHg, Z=-3.071, P<0.05; DBP10: 63.44±8.36 vs. 68.29±6.43 mmHg, t=-3.265, P <0.05; MBP10: 78.31±9.74 vs. 83.28±7.30 mmHg, t =-2.879, P<0.05].Receiver operating characteristic curve analysis showed that DBP10,the difference between baseline DBP and DBP at 10-minute (△DBP10),and the in creasing rate of DBP10(△DBPR10) were predictive factors for POTS combined with VVS,with cut-off values of 67.5 mmHg (AUC=0.687,sensitivity 67.5%,specificity 72.0%),7.5 mmHg (AUC=0.633,sensitivity 43.9%,specificity 79.3%),and -2.84% (AUC=0.631,sensitivity 92.7%,specificity 31.7%),respectively.The combined predictive value was more significant (AUC=0.709, P<0.05),with sensitivity and specificity of 70.7% and 67.1%,respectively.In terms of age,DBP10 exhibited a higher predictive value in patients aged 13-18 years,with a DBP10 cut-off of 64.5 mmHg,AUC of 0.762,sensitivity of 92.7%,and specificity of 31.7%. Conclusion:The rate of HUTT-proven VVS in POTS was 66.13%.△DBP10,DBP10 and △DBPR10 have predictive value for POTS combined with VVS.Additionally,DBP10 shows a higher predictive value in patients aged 13-18 years.


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