1.lncRNA DLEU2 regulates IKKα-mediated 131I resistance in thyroid carcinoma TPC-1 cells via the EZH2/H3K27me3 axis
ZOU Huangren ; LIU Yanlin ; ZHANG Lu ; BAI Yuke ; GAO Rui ; QIN Tiantian ; FANG Ruotong ; DENG Ziyong
Chinese Journal of Cancer Biotherapy 2026;33(4):363-372
[摘 要] 目的:探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌(TC)放射性碘抵抗的作用机制。方法:利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞(RR-TPC-1细胞)模型及裸鼠移植瘤模型,通过敲低或过表达DLEU2(si-DLEU2/OE-DLEU2)、抑制EZH2(UNC1999)、过表达IKKα(OE-IKKα)进行干预,采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果:TCGA分析显示,DLEU2在TC组织中显著上调(P < 0.001),与患者不良预后相关(P = 0.008 4),且与EZH2表达呈正相关(r = 0.390, P < 0.001);RIP证实EZH2与DLEU2存在相互作用/结合(P < 0.05)。体外实验表明,敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平,抑制NF-κB通路活化(P < 0.05或P < 0.01),抑制细胞增殖、促进凋亡(均P < 0.05)。联合敲低DLEU2与抑制EZH2进一步增强上述效应,而过表达IKKα则可部分逆转上述效应(P < 0.05或P < 0.01)。体内实验进一步证实,敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长,增加肿瘤细胞凋亡(均P < 0.01);IKKα过表达则部分逆转上述抗肿瘤效应(P < 0.05或P < 0.01)。结论:lncRNA DLEU2通过招募EZH2催化H3K27me3修饰,间接激活IKKα/NF-κB信号并形成正反馈环路,介导TPC-1细胞131I抵抗。
2.Strategies Study on DRG Subdivision of Gastrointestinal Surgery Cases
Hongxing YU ; Xinru ZHAO ; Mingju WANG ; Fuxing LI ; Rui TIAN ; Qin LUO ; Jin ZHANG ; Jie LUO
Chinese Hospital Management 2025;45(5):92-96
Objective To explore strategies for further subdivision of DRG in gastrointestinal surgery cases,providing references to enhance the differentiation of DRG subgroups.Methods A total of 5 108 gastrointestinal surgery cases were selected from a tertiary grade A hospital and a tertiary hospital in Hubei Province,spanning from January 2019 to June 30,2023,and another secondary hospital's data from 2020 and 2021.It employs single factor analysis and multiple linear regression analysis to identify factors influencing case costs.Additionally,the opinions of nine clinicans were gathered regarding factors affecting resource consumption in gastrointestinal surgery cases.The four selected case groups were further subdivided considers the peak characteristics of disease costs.It compares subdivided groups with the DRG Payment Subgroups Scheme(Version 2.0).Results Groups GB1,GB2,GC1,and GC2 were subdivided into 7,4,7,and 6 DRG groups,respectively.The coefficient of variation of each subdivided DRG were reduced,homogeneity was increased,and inter-group differentiation was increased.The results were consistent with the DRG Payment Subgroups Scheme(Version 2.0).Conclusion Based on DRG grouping,the DRG groups can be further subdivided according to the peak characteristics presented by case costs.This subdivision strategy is helpful to provide new ideas for case grouping of Medicare payment.
3.Transition of body mass index and metabolic syndrome in patients with major depressive disorder
Han QI ; Chengcheng DONG ; Rui LIU ; Xuequan ZHU ; Xuzhou LIN ; Yanshu QIN ; Zibo YU ; Haining WANG ; Lei LI ; Yuan FENG ; Ling ZHANG ; Fang YAN
Journal of Capital Medical University 2025;46(2):202-209
Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.
4.Staging system for renal tuberculosis and prognostic analysis of treatment at different stages
Chenhao GUO ; Xiao LU ; Yuyang ZHANG ; Rui ZHANG ; Wei QIN ; Linping QI ; Xiumei LI ; Panfeng SHANG
Chinese Journal of Urology 2025;46(8):581-586
Objective:To investigate the staging criteria of renal tuberculosis,and to analyze the diagnostic and therapeutic characteristics as well as prognostic outcomes at different stages.Methods:A retrospective analysis was conducted on the clinical data of 134 patients with renal tuberculosis who were admitted to the Second Hospital of Lanzhou University between January 2019 and December 2023.The study cohort included 62 males and 72 females,with a mean age of(46.63 ± 13.52)years and a mean body mass index(BMI)of(22.85 ± 3.73)kg/m 2. A total of 107 patients resided in rural areas. Sixty patients had a history of pulmonary tuberculosis. Tuberculous lesions were located in the left kidney in 72 cases and in the right kidney in 62 cases. The main presenting complaints included irritative lower urinary tract symptoms in 85 patients and systemic symptoms in 92 patients. Ureteral involvement was observed in 97 patients,bladder involvement in 32 patients,and genital involvement in 9 patients. Based on computed tomography(CT)findings,the number,extent,and degree of renal destruction caused by tuberculous lesions were comprehensively evaluated in axial,coronal,and sagittal planes. The primary staging criteria included lesion diameter(2 cm)and the proportion of renal volume involved by the lesion(one-third,one-half,and two-thirds). Renal tuberculosis was classified into three stages and six subtypes:Stage Ⅰa,a solitary lesion with a diameter ≤ 2 cm;Stage Ⅰb,a solitary lesion >2 cm or multiple lesions confined within one-third of the renal volume;Stage Ⅱa,lesions involving more than one-third but confined within one-half of the renal volume;Stage Ⅱb,lesions involving more than one-half but confined within two-thirds of the renal volume;Stage Ⅲa,lesions involving more than two-thirds of the renal volume with a glomerular filtration rate(GFR)of the affected kidney <10 ml/min;and Stage Ⅲb,complete renal calcification,presenting as an “autonephrectomy”. Among the 134 patients included in this study,7 were classified as Stage Ⅰa,17 as Stage Ⅰb,20 as Stage Ⅱa,19 as Stage Ⅱb,62 as Stage Ⅲa,and 9 as Stage Ⅲb. The severity of hydronephrosis was graded as follows:mild,renal pelvic separation <2 cm;moderate,2-3 cm;and severe,>3 cm. Prior to treatment,the mean renal pelvic separation was(1.76 ± 0.92)cm in Stage Ⅰa,(1.69 ± 0.81)cm in Stage Ⅰb,and(1.10 ± 0.82)cm in Stage Ⅱa,corresponding to mild to moderate hydronephrosis. All 7 patients in Stage Ⅰa underwent ureteroscopic examination and double-J stent placement,combined with a 6-month short-course anti-tuberculosis regimen consisting of isoniazid,rifampicin,pyrazinamide,and ethambutol for 2 months(intensive phase),followed by isoniazid and rifampicin for 4 months(continuation phase). Among the 17 patients in Stage Ⅰb,13 presented with hydronephrosis and underwent ureteroscopic examination and double-J stent placement in combination with 6 months of anti-tuberculosis therapy,while 4 patients with isolated renal tuberculosis received anti-tuberculosis therapy alone for 6 months.Of the 20 patients in Stage Ⅱa,4 with hydronephrosis underwent ureteroscopic examination and double-J stent placement plus 6 months of anti-tuberculosis therapy,whereas 16 underwent nephroureterectomy. All 19 patients in Stage Ⅱb underwent nephroureterectomy. Among the 62 patients in Stage Ⅲa,60 underwent nephroureterectomy,while 2 refused surgery and were treated with the 6-month short-course anti-tuberculosis regimen. Of the 9 patients in Stage Ⅲb,8 underwent nephroureterectomy;in 1 patient,surgery was not performed due to severe adhesions in the operative field,and the patient received the 6-month short-course anti-tuberculosis regimen instead. Follow-up assessments included clinical symptoms,erythrocyte sedimentation rate(ESR),serum creatinine,degree of renal pelvic separation,and imaging findings from urinary tract CT. Efficacy was evaluated according to the following criteria:Cure was defined as clinical stability with all of the following conditions:① improvement of systemic symptoms,including absence of flank pain,fever,and lower urinary tract irritative symptoms,with normalization of erythrocyte sedimentation rate(ESR);② negative urine culture for Mycobacterium tuberculosis;and ③ complete calcification of renal lesions and/or no evidence of tuberculous lesions at other sites. Stable disease was defined as no change in the size or extent of renal tuberculosis lesions. Progressive disease was defined as enlargement or increase in the number of tuberculous lesions or involvement of additional sites. Results:Among the 7 patients in Stage Ⅰa,follow-up imaging after treatment showed a mean renal pelvic separation of(0.44 ± 0.56)cm,which was significantly reduced compared with baseline( t = 3.909, P = 0.008). Five patients achieved cure,1 remained stable,and 1 showed disease progression and subsequently underwent nephroureterectomy,resulting in postoperative cure. In Stage Ⅰb,among 13 patients with hydronephrosis,post-treatment imaging showed a mean renal pelvic separation of(0.8 ± 0.75)cm,a statistically significant improvement from baseline( t = 5.633, P < 0.01). Six patients were cured,4 remained stable,and 3 experienced disease progression and underwent nephroureterectomy. Of the 4 patients with isolated renal tuberculosis,2 were controlled,and 2 progressed and underwent nephroureterectomy. In Stage Ⅱa,among 4 patients with tuberculous hydronephrosis,post-treatment renal pelvic separation was(1.20±0.98)cm,with no significant difference from baseline( t = -1.675, P = 0.193);these patients underwent nephroureterectomy 1-2 years later. The remaining 16 patients without hydronephrosis underwent nephroureterectomy and were cured. All 19 patients in Stage Ⅱb underwent nephroureterectomy;17 were cured,and 2 developed ipsilateral perirenal fluid collections 3 months postoperatively,which resolved spontaneously with the standard 6-month anti-tuberculosis regimen. Among 62 patients in Stage Ⅲa,60 underwent nephroureterectomy. Of these,54 were cured;1 developed a urinary tract infection within 2 weeks postoperatively;3 showed contralateral renal disease progression at 3 months;and 1 developed ipsilateral perirenal fluid at 3 months,which resolved spontaneously with standard anti-tuberculosis therapy. One patient developed solitary kidney failure 7 months postoperatively and underwent ureteral stent placement,with disease remaining stable thereafter. Two patients refused surgery and received only anti-tuberculosis therapy;during follow-up,1 patient experienced disease progression and died of disseminated tuberculosis after 1 year,while the other developed contralateral renal involvement at 3 months and received standard 6-month therapy,with disease remaining stable. Among 9 patients in Stage Ⅲb,8 underwent nephroureterectomy and were cured. One patient,with severe adhesions precluding surgery,received anti-tuberculosis therapy alone,and disease remained stable over a 2-year follow-up. Conclusions:The CT-based staging system for renal tuberculosis proposed in this study(three stages and six subtypes)effectively reflects the severity of renal lesions and clearly delineates the clinical characteristics and prognostic outcomes at each stage. Stage Ⅰ patients treated with anti-tuberculosis drugs combined with double-J stent placement demonstrated favorable outcomes and high renal preservation rates. In contrast,Stages Ⅱ and Ⅲ patients showed poor responses to anti-tuberculosis therapy combined with drainage,with a higher risk of disease progression and relatively worse prognosis,highlighting the recommendation for early nephroureterectomy of the affected kidney.
5.Protective effect of knock-down the expression of Blimp1 gene on early liver injury in CCl4-induced mouse model of liver fibrosis
Qiushi QIN ; Rui LI ; Yanxi ZHOU ; Yue ZHANG ; Ming HAN ; Liuluan ZHU
Journal of Peking University(Health Sciences) 2025;57(4):727-734
Objective:To explore the protective effect of knock-down the expression of B lymphocyte induced maturation protein 1(Blimp1)gene on early liver injury in carbon tetrachloride(CCl4)-induced mouse model of liver fibrosis.Methods:C57BL/6 mice were intraderitoneal injected with 5%CCl4 olive oil solution to create mouse model of hepatic fibrosis.The expression of Blimp1 gene in the mice was re-duced by intraderitoneal injection of short hairpin RNA(shRNA)adeno-associated virus(AAV).The mice were randomly divided into 3 groups:blank test group(n=10),CCl4+AAV-shRNA-NC group(n=10)and CCl4+AAV-shRNA-Blimp1 group(n=10).After 27 days of preparation of the CCl4 mouse model,animal materials were carried out.Western blot and real-time PCR were used to detect the levels of Blimp1,α-smooth muscle actin(α-SMA),collagen type Ⅰ alpha 1(COL1A1),collagen typeⅢ alpha 1(COL3A1),and their mRNA expression levels of liver tissue in each group.The serum of each group was separated to measure aspartate transaminase(AST)and alanine transaminase(ALT)by automatic biochemical analyzer.The pathological changes of liver tissue and the degree of liver fibrosis in the mice were detected by pathological staining including hematoxylin-eosin staining,Masson,and Sirius red.Results:The expression levels of Blimp1 protein in the liver of CCl4+AAV-shRNA-NC group(2.036±0.244,t=3.690,P=0.002)were significantly increased than that of the blank test group.In the CCl4+AAV-shRNA-Blimp1 group,the expression of Blimp1 protein decreased to the basal level(0.783±0.249,t=6.223,P=0.003).Compared with the serum levels of ALT[(1 957.8±633.6)U/L]and AST[(1 808.8±260.1)U/L]in the CCl4+AAV-shRNA-NC group,the serum levels of ALT[(894.0±360.1)U/L,t=3.998,P=0.003]and AST[(820.0±100.6)U/L,t=6.141,P=0.004]in the CCl4+AAV-shRNA-Blimp1 group were significantly decreased.The pathological re-sults of the CCl4+AAV-shRNA-Blimp1 group showed that compared with the CCl4+AAV-shRNA-NC group,the infiltration of inflammatory cells in the liver tissue was reduced and the degree of fibrosis was alleviated.The level of α-SMA(0.676±0.064,t=7.930,P=0.001),COL1A1(1.426±0.143,t=6.364,P=0.003)and COL3A1(1.124±0.198,t=3.440,P=0.026)of liver in the CCl4+AAV-shRNA-Blimp1 group were significantly decreased than that of CCl4+AAV-shRNA-NC group,and the mRNA expression levels were altered as well as their protein levels.Conclusion:Blimp1 plays an important role in CCl4-induced liver fibrosis in mice,and knock-down the expression of Blimp1 gene is beneficial to protect early liver injury in mice.
6.Research progress of cytotoxic CD4+ T cell in autoimmune diseases.
Qin ZHANG ; Rui CHI ; Fang GONG
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):161-165
Cytotoxic CD4+ T cells (CD4+ CTLs) represent a novel subset of T cells with cytotoxic effects. They recognize target cells in an antigen-specific manner, relying on class II major histocompatibility complex (MHC-II) interactions. CD4+ CTLs exert cytotoxic effects on target cells by secreting cytotoxic molecules such as granzymes, perforin, and granulysin. Recent studies have revealed their significant roles in various autoimmune diseases. This review focuses on the differentiation, phenotypic characteristics, and roles of CD4+ CTLs in different types of autoimmune disorders, aiming to provide new insights for the prevention and treatment of these diseases.
Humans
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Autoimmune Diseases/immunology*
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CD4-Positive T-Lymphocytes/immunology*
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Animals
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T-Lymphocytes, Cytotoxic/immunology*
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Perforin/immunology*
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Granzymes/immunology*
7.Machine learning models established to distinguish OA and RA based on immune factors in the knee joint fluid.
Qin LIANG ; Lingzhi ZHAO ; Yan LU ; Rui ZHANG ; Qiaolin YANG ; Hui FU ; Haiping LIU ; Lei ZHANG ; Guoduo LI
Chinese Journal of Cellular and Molecular Immunology 2025;41(4):331-338
Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans
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Arthritis, Rheumatoid/metabolism*
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Machine Learning
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Male
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Female
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Middle Aged
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Aged
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Synovial Fluid/immunology*
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Osteoarthritis, Knee/metabolism*
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Knee Joint/metabolism*
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ROC Curve
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Diagnosis, Differential
8.Liang-Ge-San Decoction Ameliorates Acute Respiratory Distress Syndrome via Suppressing p38MAPK-NF-κ B Signaling Pathway.
Quan LI ; Juan CHEN ; Meng-Meng WANG ; Li-Ping CAO ; Wei ZHANG ; Zhi-Zhou YANG ; Yi REN ; Jing FENG ; Xiao-Qin HAN ; Shi-Nan NIE ; Zhao-Rui SUN
Chinese journal of integrative medicine 2025;31(7):613-623
OBJECTIVE:
To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments.
METHODS:
The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments.
RESULTS:
A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01).
CONCLUSION
LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology*
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Respiratory Distress Syndrome/enzymology*
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p38 Mitogen-Activated Protein Kinases/metabolism*
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NF-kappa B/metabolism*
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Animals
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Signal Transduction/drug effects*
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Molecular Docking Simulation
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Humans
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Male
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Network Pharmacology
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Apoptosis/drug effects*
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Mice
9.A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment.
Rui LIAO ; Yuequan WANG ; Ziqi LIN ; Yuting WANG ; Hongyuan ZHANG ; Qin CHEN ; Shenwu ZHANG ; Jin SUN ; Zhonggui HE ; Cong LUO
Acta Pharmaceutica Sinica B 2025;15(6):3273-3290
Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.
10.Diffusion-weighted imaging features of patent foramen ovale-related cryptogenic stroke and correlation of infarct size with cardiac CT characteristics
Shuang ZHANG ; Chong ZHENG ; Rui QIN ; Wenlei GENG ; Lijie SUN ; Jing LI ; Jie LU
Chinese Journal of Cerebrovascular Diseases 2025;22(7):465-473
Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or<15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P<0.016 7),while other baseline characteristics showed no significant differences(all P>0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62%[97/116]vs.61.11%[22/36],P<0.016 7),but a lower proportion than the AF group(83.62%[97/116]vs.98.75%[79/80],P<0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41%[55/116]vs.11.11%[4/36]and 6.25%[5/80],respectively,both P<0.016 7)and infarcts with a maximum diameter<15 mm compared to both AAE and AF groups(66.38%[77/116]vs.36.11%[13/36]and 11.25%[9/80],respectively,both P<0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59%[32/116]vs.69.44%[25/36]in AAE group and 67.50%[54/80]in AF group,both P<0.016 7),but a higher proportion of posterior circulation infarcts(62.07%[72/116]vs.16.67%[6/36]in AAE group and 8.75%[7/80]in AF group,both P<0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97%[22/116]vs.66.67%[24/36]in AAE group and 52.50%[42/80]in AF group,both P<0.016 7),while posterior cerebral artery infarcts were more common(48.28%[56/116]vs.8.33%[3/36]in AAE group and 8.75%[7/80]in AF group,both P<0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P>0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

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