OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Purpose To explore the clinical and pathological characteristics of gastric amphicrine carcinoma(AC).Methods Clinical data of 12 patients with gastric AC were collected,and their clinical pathological character-istics and histological morphology were observed.Immunohistochemical staining,special staining,and electron micros-copy techniques were used to analyze their immune phenotype and ultrastructure.Molecular pathology was used to de-tect microsatellite status.Relevant literature was reviewed.Results Ten cases of gastric AC were located at the junc-tion of the esophagus and stomach/cardia,1 case at the gastric angle,and 1 case in the gastric antrum.The average maximum diameter of tumors was 4.25 cm.There were different proportions of tumor cells with signet-ring like charac-teristics in all cases.Four cases had neuroendocrine carcinoma components,and another 4 had adenocarcinoma.Elev-en cases had nerve invasion and vascular cancer thrombus.Eleven cases invaded the serosal layer/submucosal layer,and 1 case invaded the submucosal layer.Ten cases had lymph node metastasis.All 12 cases showed diffuse expression of CKpan and Syn,with 3 cases showed diffuse expression of CgA and 7 cases showed diffuse expression of CD56.The average proliferation index of Ki67 was 78.9％.Special staining showed clear intracellular mucus.Electron microscopy examination revealed electron dense particles and mucus particles within the tumor cells.A total of 10 patients were fol-lowed up,of which 7 survived,and 3 patients died from multiple systemic metastases at 0,24,and 30 months postop-eratively.Conclusion Gastric AC was more common in the junction of the esophagus and stomach/cardia,and histol-ogy shows a higher invasiveness.Their clear diagnosis depends on histological morphology,immunohistochemistry,and special staining.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

Aim To explore the relationship between serum uric acid(UA)/creatinine(Cr),homocysteine(Hcy),apolipoprotein A1(ApoA1)levels and plaque stability in patients with carotid atherosclerosis(CAS)and the pre-dictive value for secondary acute cerebral infarction(ACI).Methods 138 patients with CAS were selected as the re-search subjects and further divided into stable plaque group and unstable plaque group based on the stability of plaques.Heathy individuals undergoing physical examinations were selected as the control group.Enzyme cycling method was used to detect Hcy level,latex enhanced immunoturbidimetry method was used to detect ApoA1 level,uricase method was used to detect UA level,enzyme method was used to detect Cr level,and UA/Cr ratio was calculated.Baseline data and labo-ratory indicators in the no plaque group,stable plaque group and unstable plaque group were compared.The relationship between laboratory indicators and intima-media thickness(IMT)was analyzed using Spearman correlation analysis.Cox regression model was used for univariate and multivariate analysis of secondary ACI in patients with CAS,and ROC curve was used to evaluate the predictive value of serum UA/Cr,Hcy and ApoA1 levels for it.Results Among 138 patients with CAS,there were 74 cases in the stable plaque group and 64 cases in the unstable plaque group;there were 46 cases of secondary ACI.There were 42 cases in the control group.Compared with the control group,the stable plaque group and unstable plaque group had lower levels of serum ApoA1 and high density lipoprotein cholesterol(HDLC),and higher levels of serum UA/Cr,Hcy,low density lipoprotein cholesterol(LDLC)and IMT(P＜0.05).Spearman correlation analysis showed that IMT in the plaque group was positively correlated with serum UA/Cr and Hcy levels(r=0.535 and r=0.681,P＜0.05),and negatively correlated with ApoA1 levels(r=-0.594,P＜0.05).Cox regression analysis showed that un-stable plaques,high serum UA/Cr and Hey levels were risk factors for secondary ACI,while high serum ApoA1 levels were protective factors for secondary ACI(P＜0.05).ROC curve analysis showed that the sensitivity and specificity of combi-ning serum UA/Cr,Hcy and ApoA1 for predicting secondary ACI in the CAS patients were 85.45％and 82.67％,respec-tively,with an AUC of 0.920,which was higher than the individual diagnosis of UA/Cr,Hcy and ApoA1.Conclu-sions The levels of serum UA/Cr and Hcy are significantly positively correlated with plaque formation and stability in the CAS patients,while ApoA1 is significantly negatively correlated with them.These three factors are independent influen-cing factors for secondary ACI in the CAS patients,and their combined prediction of ACI has a higher efficacy.

Aim To explore the relationship between serum uric acid(UA)/creatinine(Cr),homocysteine(Hcy),apolipoprotein A1(ApoA1)levels and plaque stability in patients with carotid atherosclerosis(CAS)and the pre-dictive value for secondary acute cerebral infarction(ACI).Methods 138 patients with CAS were selected as the re-search subjects and further divided into stable plaque group and unstable plaque group based on the stability of plaques.Heathy individuals undergoing physical examinations were selected as the control group.Enzyme cycling method was used to detect Hcy level,latex enhanced immunoturbidimetry method was used to detect ApoA1 level,uricase method was used to detect UA level,enzyme method was used to detect Cr level,and UA/Cr ratio was calculated.Baseline data and labo-ratory indicators in the no plaque group,stable plaque group and unstable plaque group were compared.The relationship between laboratory indicators and intima-media thickness(IMT)was analyzed using Spearman correlation analysis.Cox regression model was used for univariate and multivariate analysis of secondary ACI in patients with CAS,and ROC curve was used to evaluate the predictive value of serum UA/Cr,Hcy and ApoA1 levels for it.Results Among 138 patients with CAS,there were 74 cases in the stable plaque group and 64 cases in the unstable plaque group;there were 46 cases of secondary ACI.There were 42 cases in the control group.Compared with the control group,the stable plaque group and unstable plaque group had lower levels of serum ApoA1 and high density lipoprotein cholesterol(HDLC),and higher levels of serum UA/Cr,Hcy,low density lipoprotein cholesterol(LDLC)and IMT(P＜0.05).Spearman correlation analysis showed that IMT in the plaque group was positively correlated with serum UA/Cr and Hcy levels(r=0.535 and r=0.681,P＜0.05),and negatively correlated with ApoA1 levels(r=-0.594,P＜0.05).Cox regression analysis showed that un-stable plaques,high serum UA/Cr and Hey levels were risk factors for secondary ACI,while high serum ApoA1 levels were protective factors for secondary ACI(P＜0.05).ROC curve analysis showed that the sensitivity and specificity of combi-ning serum UA/Cr,Hcy and ApoA1 for predicting secondary ACI in the CAS patients were 85.45％and 82.67％,respec-tively,with an AUC of 0.920,which was higher than the individual diagnosis of UA/Cr,Hcy and ApoA1.Conclu-sions The levels of serum UA/Cr and Hcy are significantly positively correlated with plaque formation and stability in the CAS patients,while ApoA1 is significantly negatively correlated with them.These three factors are independent influen-cing factors for secondary ACI in the CAS patients,and their combined prediction of ACI has a higher efficacy.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.

Purpose To explore the clinical and pathological characteristics of gastric amphicrine carcinoma(AC).Methods Clinical data of 12 patients with gastric AC were collected,and their clinical pathological character-istics and histological morphology were observed.Immunohistochemical staining,special staining,and electron micros-copy techniques were used to analyze their immune phenotype and ultrastructure.Molecular pathology was used to de-tect microsatellite status.Relevant literature was reviewed.Results Ten cases of gastric AC were located at the junc-tion of the esophagus and stomach/cardia,1 case at the gastric angle,and 1 case in the gastric antrum.The average maximum diameter of tumors was 4.25 cm.There were different proportions of tumor cells with signet-ring like charac-teristics in all cases.Four cases had neuroendocrine carcinoma components,and another 4 had adenocarcinoma.Elev-en cases had nerve invasion and vascular cancer thrombus.Eleven cases invaded the serosal layer/submucosal layer,and 1 case invaded the submucosal layer.Ten cases had lymph node metastasis.All 12 cases showed diffuse expression of CKpan and Syn,with 3 cases showed diffuse expression of CgA and 7 cases showed diffuse expression of CD56.The average proliferation index of Ki67 was 78.9％.Special staining showed clear intracellular mucus.Electron microscopy examination revealed electron dense particles and mucus particles within the tumor cells.A total of 10 patients were fol-lowed up,of which 7 survived,and 3 patients died from multiple systemic metastases at 0,24,and 30 months postop-eratively.Conclusion Gastric AC was more common in the junction of the esophagus and stomach/cardia,and histol-ogy shows a higher invasiveness.Their clear diagnosis depends on histological morphology,immunohistochemistry,and special staining.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.