1.Differences in postural control ability between older adults with mild cognitive impairment and those with normal cognition under different single-task and dual-task conditions
Yuxin ZHANG ; Cong YU ; Cui ZHANG ; Jianjun DING ; Yan CHEN
Chinese Journal of Tissue Engineering Research 2025;29(8):1643-1649
BACKGROUND:The decreased postural control ability due to mild cognitive impairment in elderly people leads to the increased risk of falls.Dual-task is the primary research paradigm for evaluating the relationship between cognition and postural control in the scenes close to real life.The sample entropy of the plantar center of pressure(COP)displacement during standing can represent the complexity of postural control. OBJECTIVE:Based on the COP displacement sample entropy,to analyze the differences in postural stability characteristics and control strategies between older adults with mild cognitive impairment and cognitively normal older adults during the dual-task with postural control and spatial working memory,aiming to explore the impact of cognitive impairment on the postural control ability during standing. METHODS:Sixteen older adults with mild cognitive impairment and 17 cognitively normal older adults were eligible and selected for the study.They completed five test tasks,including spatial working memory,double-feet balance stance,Romberg stance,double-feet balance stance-spatial working memory dual-task,and Romberg stance-spatial working memory dual-task,with three valid completions of each task.The plantar COP data were collected by the Kistler 3D force platform.The indicators included cognitive behavior(cognitive score and reaction time)and kinematic indexes(COP displacement and sample entropy). RESULTS AND CONCLUSION:The older adults with mild cognitive impairment performed the spatial working memory task with the greatest cognitive score and the shortest reaction time,the double-feet balance stance-spatial working memory dual-task with moderate cognitive score and reaction time,and the Romberg stance-spatial working memory dual-task with the smallest cognitive score and the longest reaction time,where the differences were significant among the tasks(P<0.05).In the older adults with mild cognitive impairment,the anterior-posterior and medial-lateral COP displacements were significantly greater,and their sample entropy values were significantly smaller in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task than in the double-feet balance stance and Romberg stance tasks(P<0.05).In the spatial working memory task,there were no significant differences in cognitive score and reaction time between the both groups(P>0.05);however,in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,cognitive scores were significantly smaller and reaction times were longer in the older adults with mild cognitive impairment compared with the cognitively normal older adults(P<0.05).In the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,the older adults with mild cognitive impairment exhibited significantly greater anterior-posterior and medial-lateral COP displacements and significantly smaller sample entropy values compared with the cognitively normal older adults(P<0.05).All findings indicate that compared with cognitively normal older adults,older adults with mild cognitive impairment exhibit smaller complexity,poorer systematic adaption and decreased automatic regulation of the postural control during performing the dual-tasks,who are more susceptible to spatial working memory interference,leading to the increased risk of falls.
2.Oxidative Stress of Qidan Tangshen Granules (芪丹糖肾颗粒) in Treatment of 95 Patients with Early Diabetic Kidney Disease with Qi Deficiency,Blood Stasis,and Kidney Deficiency Syndrome:A Double-Blind,Double-Simulated,Randomized Controlled Trial
Jie ZHANG ; Yilei CONG ; Tengfei WU ; Qin LIU ; Yue YUAN ; Shilei CUI ; Hua YANG
Journal of Traditional Chinese Medicine 2025;66(7):695-703
ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules (芪丹糖肾颗粒, QTG) in the treatment of early diabetic kidney disease (DKD) with qi deficiency, blood stasis, and kidney deficiency syndrome, and to explore its mechanism. MethodsA double-blind, double-simulated method was used to enroll 200 patients with early DKD and qi deficiency, blood stasis, and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group (100 cases) and the control group (100 cases). The treatment group received QTG plus a valsartan capsule simulant, while the control group received valsartan capsules plus a QTG simulant, both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio (UACR). Secondary outcomes included estimated glomerular filtration rate (eGFR), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycated hemoglobin (HbA1c), and traditional Chinese medicine (TCM) syndrome scores (including individual symptom scores for fatigue, dull complexion, soreness and weakness of the waist and knees, headache and chest pain, irritability, spontaneous sweating, thirst and polydipsia, polyphagia, polyuria, numbness of the limbs, and the total TCM syndrome score). Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine (8-OHDG), 3-nitrotyrosine (3-NT), and superoxide dismutase (SOD) were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment, and routine blood tests, urinalysis, and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study (95 in the treatment group and 96 in the control group). The treatment group showed significant reductions in UACR, FBG, PBG, and HbA1c levels after treatment (P<0.05 or P<0.01). The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased (P<0.05 or P<0.01). Compared to the control group, the treatment group had signi-ficantly lower UACR, FBG, PBG levels, and total TCM syndrome scores, sinlge symptoms scores except for polyphagia and limb numbness (P<0.05 or P<0.01). Among 40 randomly selected patients (21 cases in the treatment group and 19 cases in the control group) for oxidative stress analysis, there were no significant differences in SOD, 3-NT, and 8-OHDG levels before and after treatment within or between groups (P>0.05). The overall effective rate in the treatment group was 64.2% (61/95) and 39.6% (38/96) in the control group, while the TCM syndrome efficacy rates were 80.0% (76/95) and 24.0% (23/96), respectively, with the treatment group showing superior efficacy (P<0.01). No significant differences were observed in routine blood tests, urinalysis, or liver function indices before and after treatment in either group (P>0.05). The incidence of adverse reactions was 8.4% (8/95) in the treatment group and 9.4% (9/96) in the control group, with no statistically significant difference (P>0.05). ConclusionQTG can effectively reduce UACR and blood glucose levels, alleviate clinical symptoms, and improve clinical efficacy in patients with early DKD with qi deficiency, blood stasis, and kidney deficiency syndrome. The treatment is well-tolerated and safe, with no significant impact on oxidative stress markers.
3.Evaluation of operation quality of measles surveillance system in Hebei Province in 2020 - 2023
Shiheng CUI ; Xiaomeng XU ; Li SUN ; Yafei WANG ; Wei WANG ; Yanli CONG ; Jinghui WANG
Journal of Public Health and Preventive Medicine 2025;36(2):26-29
Objective To analyze the operation of Measles Surveillance System (MSS) in Hebei Province, and to provide evidence for measles elimination. Methods Measles surveillance data was collected from the MSS from 2020 to 2023, and a modified weighted technology for order preference by similarity to an ideal solution (TOPSIS) method was used to evaluate the surveillance indexes of measles in Hebei Province. Results The operation quality of the measles surveillance system in Hebei Province was improved year by year, with the highest quality in 2023, and all the indicators reached the monitoring program standards. The quality of measles surveillance system was not balanced among cities, and the main influencing factor was the substandard sensitivity indicators. The quality of measles surveillance system was the highest in Baoding City and the lowest in Zhangjiakou City. Conclusion The measles surveillance system in Hebei province is running well, and the sensitivity of the surveillance system should be improved to keep the high-quality operation of the surveillance system.
4.The Mechanism of Exercise Regulating Intestinal Flora in The Prevention and Treatment of Depression
Lei-Zi MIN ; Jing-Tong WANG ; Qing-Yuan WANG ; Yi-Cong CUI ; Rui WANG ; Xin-Dong MA
Progress in Biochemistry and Biophysics 2025;52(6):1418-1434
Depression, a prevalent mental disorder with significant socioeconomic burdens, underscores the urgent need for safe and effective non-pharmacological interventions. Recent advances in microbiome research have revealed the pivotal role of gut microbiota dysbiosis in the pathogenesis of depression. Concurrently, exercise, as a cost-effective and accessible intervention, has demonstrated remarkable efficacy in alleviating depressive symptoms. This comprehensive review synthesizes current evidence on the interplay among exercise, gut microbiota modulation, and depression, elucidating the mechanistic pathways through which exercise ameliorates depressive symptoms via the microbiota-gut-brain (MGB) axis. Depression is characterized by gut microbiota alterations, including reduced alpha and beta diversity, depletion of beneficial taxa (e.g., Bifidobacterium, Lactobacillus, and Coprococcus), and overgrowth of pro-inflammatory and pathogenic bacteria (e.g., Morganella, Klebsiella, and Enterobacteriaceae). Metagenomic analyses reveal disrupted metabolic functions in depressive patients, such as diminished synthesis of short-chain fatty acids (SCFAs), impaired tryptophan metabolism, and dysregulated bile acid conversion. For instance, Bifidobacterium longum deficiency correlates with reduced synthesis of neuroactive metabolites like homovanillic acid, while decreased Coprococcus abundance limits butyrate production, exacerbating neuroinflammation. Furthermore, elevated levels of indole derivatives from Clostridium species inhibit serotonin (5-HT) synthesis, contributing to depressive phenotypes. These dysbiotic profiles disrupt the MGB axis, triggering systemic inflammation, neurotransmitter imbalances, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Exercise exerts profound effects on gut microbiota composition, diversity, and metabolic activity. Longitudinal studies demonstrate that sustained aerobic exercise increases alpha diversity, enriches SCFA-producing genera (e.g., Faecalibacterium prausnitzii, Roseburia, and Akkermansia), and suppresses pathobionts (e.g., Desulfovibrio and Streptococcus). For example, a meta-analysis of 25 trials involving 1 044 participants confirmed that exercise enhances microbial richness and restores the Firmicutes/Bacteroidetes ratio, a biomarker of metabolic health. Notably, endurance training promotes Veillonella proliferation, which converts lactate into propionate, enhancing energy metabolism and delaying fatigue. Exercise also strengthens intestinal barrier integrity by upregulating tight junction proteins (e.g., ZO-1, occludin), thereby reducing lipopolysaccharide (LPS) translocation and systemic inflammation. However, excessive exercise may paradoxically diminish microbial diversity and exacerbate intestinal permeability, highlighting the importance of moderate intensity and duration. Exercise ameliorates depressive symptoms through multifaceted interactions with the gut microbiota, primarily via 4 interconnected pathways. First, exercise mitigates neuroinflammation by elevating anti-inflammatory SCFAs such as butyrate, which suppresses NF-κB signaling to attenuate microglial activation and oxidative stress in the hippocampus. Animal studies demonstrate that voluntary wheel running reduces hippocampal TNF‑α and IL-17 levels in stress-induced depression models, while fecal microbiota transplantation (FMT) from exercised mice reverses depressive behaviors by modulating the TLR4/NF‑κB pathway. Second, exercise regulates neurotransmitter dynamics by enriching GABA-producing Lactobacillus and Bifidobacterium, thereby counteracting neuronal hyperexcitability. Aerobic exercise also enhances the abundance of Lactobacillus plantarum and Streptococcus thermophilus, which facilitate 5-HT and dopamine synthesis. Clinical trials reveal that 12 weeks of moderate exercise increases fecal Coprococcus and Blautia abundance, correlating with improved 5-HT bioavailability and reduced depression scores. Third, exercise normalizes HPA axis hyperactivity by reducing cortisol levels and restoring glucocorticoid receptor sensitivity. In rodent models, chronic stress-induced corticosterone elevation is reversed by probiotic supplementation (e.g., Lactobacillus), which enhances endocannabinoid signaling and hippocampal neurogenesis. Furthermore, exercise upregulates brain-derived neurotrophic factor (BDNF) via microbial metabolites like butyrate, promoting histone acetylation and synaptic plasticity. FMT experiments confirm that exercise-induced microbiota elevates prefrontal BDNF expression, reversing stress-induced neuronal atrophy. Fourth, exercise reshapes microbial metabolic crosstalk, diverting tryptophan metabolism toward 5-HT synthesis instead of neurotoxic kynurenine derivatives. Butyrate inhibits indoleamine 2,3-dioxygenase (IDO), a key enzyme in the kynurenine pathway linked to depression. Concurrently, exercise-induced Akkermansia enrichment enhances mucin production, fortifies the gut barrier, and reduces LPS-driven neuroinflammation. Collectively, these mechanisms underscore exercise as a potent modulator of the microbiota-gut-brain axis, offering a holistic approach to alleviating depression through microbial and neurophysiological synergy. Current evidence supports exercise as a potent adjunct therapy for depression, with personalized regimens (e.g., aerobic, resistance, or yoga) tailored to individual microbiota profiles. However, challenges remain in optimizing exercise prescriptions (intensity, duration, and type) and integrating them with probiotics, prebiotics, or FMT for synergistic effects. Future research should prioritize large-scale randomized controlled trials to validate causality, multi-omics approaches to decipher MGB axis dynamics, and mechanistic studies exploring microbial metabolites as therapeutic targets. The authors advocate for a paradigm shift toward microbiota-centric interventions, emphasizing the bidirectional relationship between physical activity and gut ecosystem resilience in mental health management. In conclusion, this review underscores exercise as a multifaceted modulator of the gut-brain axis, offering novel insights into non-pharmacological strategies for depression. By bridging microbial ecology, neuroimmunology, and exercise physiology, this work lays a foundation for precision medicine approaches targeting the gut microbiota to alleviate depressive disorders.
5.Study on the Mechanism of Piperlongumine Inducing Ferroptosis in K562/ADR Cells through the miR-214-3p/GPX4 Pathway.
Ting ZHANG ; Cui-Cui WANG ; Cong ZHU ; Xin-Yu ZHOU ; Xiu-Hong JIA
Journal of Experimental Hematology 2025;33(4):1007-1015
OBJECTIVE:
To investigate the effect of piperlongumine(PL) on the proliferation and ferroptosis of human adriamycin-resistant chronic myeloid leukemia K562/ADR cells, and to explore its possible molecular mechanism.
METHODS:
CCK-8 assay was used to detect the effect of PL on the survival rate of K562/ADR cells and to screen the appropriate drug concentration. After K562/ADR cells were treated with low, medium and high concentrations of PL(2, 4, and 6 μmol/L), EdU proliferation assay and plate colony formation assay were used to detect cell proliferation and colony formation ability. CCK-8 assay was used to detect the effects of different inhibitors (Fer-1, Z-VAD, Nec-1) combined with PL on cell proliferation. The intracellular Fe2+, ROS, malondialdehyde(MDA) and glutathine(GSH) contents were respectively detected by iron ion colorimetry, DCFH-DA fluorescent probe, MDA and GSH kits. RT-qPCR and Western blot were respectively used to detect the expression level of GPX4 mRNA and protein in cells. Bioinformatics websites predicted miRNA that could target and regulate GPX4 . RT-qPCR was used to detect the effects of different concentrations of PL on the expression levels of the predicted miRNA. Dual luciferase gene reporter assay was used to verify the targeting relationship between miR-214-3p and GPX4 . After treating cells with PL or PL+miR-214-3p inhibitor, the Fe2+, ROS, MDA, GSH centents and GPX4 protein expression levels in cells were detected.
RESULTS:
PL inhibited K562/ADR cell proliferation in a concentration-dependent manner(r =0.979). Compared with the blank control group, the survival rate, EdU positive cells rate in low, medium and high concentration PL groups were significantly decreased (P < 0.01). Compared with the PL group alone, the survival rate of cells in the Z-VAD+PL group was increased slightly (P < 0.05). The cell survival rate was significantly increased in medium or high concentration PL+Fer-1 group (P < 0.01). Compared with blank control group, ROS expression level in low concentration PL group was slightly increased (P < 0.05), and GSH content was slightly decreased (P < 0.05). In medium and high concentration PL groups, the contents of Fe2+, ROS and MDA were significantly increased (P < 0.01), while the contents of GSH, expression of GPX4 mRNA and protein were significantly decreased(P < 0.01). Bioinformatics prediction and double luciferase reporter gene experiment confirmed the targeting relationship between GPX4 and miR-214-3p. Compared with the blank control group, the expression level of miR-214-3p in cells of medium and high concentration PL groups was significantly increased (P < 0.01). Compared with PL group alone, the intracellular Fe2+, ROS and MDA contents in PL+miR-214-3p inhibitor group were all decreased (P < 0.01), while GSH content and GPX4 protein expression levels were significantly increased (P < 0.01).
CONCLUSION
Medium and high concentrations of PL can inhibit the proliferation of K562/ADR cells by inducing ferroptosis, which is related to the regulation of miR-214-3p pathway.
Humans
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Ferroptosis/drug effects*
;
MicroRNAs/metabolism*
;
Dioxolanes/pharmacology*
;
Cell Proliferation/drug effects*
;
K562 Cells
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Reactive Oxygen Species
;
Doxorubicin/pharmacology*
;
Signal Transduction
;
Piperidones
6.The influence of microvessel density and microlymphatic vessel density on prognosis in hypopharyngeal carcinoma and the construction.
Cong XU ; Lanzhen CUI ; Xiaoxiao LIU ; Jing BAI ; Lijun ZHANG ; Yu PENG ; Xiaoming LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1143-1149
Objective:This study aims to investigate the influence of microvessel density(MVD) and microlymphatic vessel density(MLVD) on the prognosis of patients with hypopharyngeal squamous cell carcinoma(HPSCC) and to develop a nomogram prediction model for prognosis based on pathological characteristics. Methods:A retrospective analysis was conducted on clinicopathological and follow-up data from HPSCC patients who underwent surgical treatment at our institution between June 2010 and June 2020. Immunohistochemical staining was performed on tumor tissues and adjacent normal margin tissues to evaluate MVD and MLVD. The associations among MVD, MLVD, and clinicopathological features were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors affecting overall survival(OS). Based on these findings, a nomogram model was constructed and its predictive accuracy was assessed using C-index, receiver operating characteristic(ROC) curve, and calibration curve. Results:Both MVD and MLVD were significantly higher in HPSCC tumor tissues compared to normal tissues. Patients in the high MVD and high MLVD groups exhibited significantly lower OS rates than those in the low MVD and low MLVD groups. Multivariate Cox regression analysis revealed that N stage, recurrence, nerve invasion, lymph node capsule invasion, MVD, and MLVD were independent prognostic factors of OS. Based on these factors, a nomogram prognosis model was successfully constructed. The nomograms demonstrated superior performance in terms of C-index, area under the ROC curve, and calibration, outperforming the AJCC TNM staging system. Conclusion:Elevated MVD and MLVD levels are associated with poorer prognosis in HPSCC patients. The nomogram model based on pathological features provides valuable insights for clinical assessment and decision-making.
Humans
;
Hypopharyngeal Neoplasms/blood supply*
;
Prognosis
;
Retrospective Studies
;
Microvascular Density
;
Nomograms
;
Lymphatic Vessels/pathology*
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Male
;
Female
;
Middle Aged
;
Carcinoma, Squamous Cell/blood supply*
;
Microvessels/pathology*
;
Lymphatic Metastasis
;
Survival Rate
7.A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer.
Kun WANG ; Cong WANG ; Hange YANG ; Gong CHEN ; Ke WANG ; Peihong JI ; Xudong SUN ; Xuegong FAN ; Jie MA ; Zhencun CUI ; Xingkai WANG ; Hao TIAN ; Dengfu WU ; Lu WANG ; Zhimin WANG ; Jiangyan LIU ; Juan YI ; Kuan HU ; Hailong ZHANG ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(10):4995-5009
Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8+ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.
8.Construction of diagnostic model for Alzheimer's disease and immune analysis based on bioinformatics and machine learning
Linrui XU ; Yiyu ZHANG ; Jiaqi CUI ; Xianzhu CONG ; Shuang LI ; Jiayu GE ; Yujia KONG ; Suzhen WANG ; Fuyan SHI ; Jinrong WANG
Journal of Jilin University(Medicine Edition) 2025;51(4):1039-1051
Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.
9.Dihydroartemisinin suppresses cancer-associated fibroblast-mediated tumor angiogenesis and lymphangiogenesis in hypopharyngeal squamous cell carcinoma
Lanzhen CUI ; Cong XU ; Xiaoxiao LIU ; Jing BAI ; Lijun ZHANG ; Yu PENG ; Xiaoming LI
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(6):341-347
OBJECTIVE To explore the effects of dihydroartemisinin(DHA)on the functions of cancer-associated fibroblasts(CAFs)in the tumor microenvironment in hypopharyngeal squamous cell carcinoma(HPSCC).METHODS The influence of conditioned media from CAFs and normal fibroblasts(NFs)on tube formation was assessed using a tube formation assay.Secreted protein levels of IL-6,VEGFA,and VEGFC were measured by immunofluorescence and ELISA.Western blotting was used to evaluate the expression of α-SMA,p-STAT3,STAT3,VEGF-A,and VEGF-C within the STAT3 signaling pathway.After treatment with DHA,the optimal concentration for DHA's effect was determined using CCK8 assays and morphological observations of cells.The impact of DHA on angiogenesis was analyzed through tube formation assays,changes in IL-6 expression were detected using ELISA and immunofluorescence,and alterations in α-SMA,p-STAT3,and STAT3 expression were examined by Western blot.RESULTS Both CAFs and NFs exhibited pro-angiogenic and pro-lymphangiogenic effects,with CAFs showing a more pronounced impact.Activated CAFs overexpressed and secreted high levels of IL-6,VEGF-A,and VEGF-C.The concentration of IL-6 in the conditioned medium supernatants of CAF1 and CAF2 was significantly higher than that of NF1 and NF2(P1<0.001,P2<0.05).Similarly,the concentration of VEGF-A was significantly increased(P1<0.05,P2<0.01),and the concentration of VEGF-C was also significantly increased(P1<0.05,P2<0.01).Treatment with DHA inhibited the activated state of CAFs,reducing the expression and secretion of IL-6 and p-STAT3,thereby suppressing tube formation.CONCLUSION Our findings indicate that CAFs promote angiogenesis and lymphangiogenesis in HPSCC via activation of the STAT3 pathway.DHA effectively inhibits this process,suggesting a potential new therapeutic strategy for the treatment of HPSCC.
10.Relationship between skin injury outcome and urinary arsenic methylation metabolites levels in people exposed to arsenic through drinking water
Xinye LI ; Danyu DENG ; Fan ZHAO ; Cong LIU ; Mengxin LI ; Zhen DI ; Na CUI ; Yijun LIU ; Chang KONG ; Binggan WEI ; Yanhong LI ; Yajuan XIA ; Zhiwei GUO
Chinese Journal of Endemiology 2024;43(6):446-451
Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.


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