Cuproptosis, a recently identified form of regulated cell death, holds therapeutic promise in cancer. However, the mechanisms governing copper homeostasis and their impact on the immune landscape of clear cell renal cell carcinoma (ccRCC) remain poorly understood. A cuproptosis-related risk model was constructed to identify key prognostic factors. The role of ATP7B in ccRCC was validated using clinical cohorts, in vitro assays, and xenograft models. Mechanistic studies including Co-IP, ubiquitination assays, and Western blot were employed to elucidate the RNF186-p62-ATP7B axis. An autophagy-targeting chimera (ATAUTAC) was developed to evaluate its therapeutic and immunomodulatory potential. High ATP7B expression correlated with poor prognosis and immune evasion in ccRCC. We found that the E3 ligase RNF186 catalyzes K63-linked ubiquitination of ATP7B, driving its selective autophagic degradation via the receptor p62. In ccRCC, RNF186 downregulation leads to ATP7B accumulation, thereby limiting copper-induced proteotoxic stress. Our developed ATAUTAC effectively degraded ATP7B, disrupted mitochondrial TCA cycle metabolism, and induced canonical cuproptosis. Combining ATAUTAC with anti-PD-1 therapy significantly suppressed tumor growth and prolonged survival in vivo. Mechanistically, ATAUTAC-induced metabolic remodeling was accompanied by PD-L1 downregulation, enhanced CD8+ T-cell infiltration, pro-inflammatory cytokine release, and a shift of macrophages toward an M1-like anti-tumor phenotype. This study identifies the RNF186-p62-ATP7B axis as a critical regulator of copper homeostasis in ccRCC. Targeting ATP7B via ATAUTAC offers a potent strategy to induce cuproptosis and sensitize ccRCC to immunotherapy.

Conventional approaches for the detection and surveillance of non-muscle invasive bladder cancer (NMIBC) remain invasive, burdensome, and costly. The utLIFE-UC assay, designed to identify mutations and large copy number variations in urine, has demonstrated high accuracy in detecting urothelial carcinoma. Here, we assessed its efficacy in early detection of NMIBC, identifying minimal residual disease, and monitoring recurrence. Among 108 consecutive NMIBC patients evaluated, utLIFE-UC exhibited a sensitivity of 90.5% in diagnosing NMIBC, with comparable performance in detecting both de novo and recurrent NMIBC. For patients undergoing repeat transurethral resection of bladder tumor (Re-TURBT), the assay accurately identified all cases with residual tumor, achieving a 100% negative predictive value. Positive postoperative utLIFE-UC results before the first follow-up cystoscopy predicted a higher risk of future relapse. A positive test result at any time following TURBT was correlated with poorer recurrence-free survival, whereas sustained negative test results indicated recurrence-free status. Moreover, utLIFE-UC could predict recurrence with a median lead time of 73.5 days prior to clinical confirmation. As the first prospective, longitudinal analysis of urinary tumor DNA in NMIBC, this study highlights the potential of utLIFE-UC to enable earlier recurrence detection and improve risk stratification, potentially obviating unnecessary Re-TURBT and surveillance cystoscopies.

4531 Background: FRUSICA-2 (NCT05522231), a randomized, open-label, controlled phase 2/3 study, demonstrated a significant efficacy of F plus S vs A or E in previously treated advanced RCC (BIRC-assessed mPFS 22.21 vs 6.90 mo; HR 0.373, p<0.0001; ORR 60.5% vs 24.3%, OR 4.622, p<0.0001; D Ye, et al; 2025 ESMO). Given the IMDC classification as the most common prognostic model and PD-L1 expression has demonstrated prognostic value across various cancer types, we conducted this exploratory subgroup analysis to evaluate clinical outcomes by baseline scores of IMDC risk factors and PD-L1 expression. Methods: Patients (pts) with histologically confirmed advanced RCC previously treated with VEGFR-TKI were randomized 1:1 to receive either F (5 mg QD, 2 weeks on/1 week off) plus S (200 mg iv, every 3 weeks), or investigator's choice of A (5 mg twice daily) or E (10 mg once daily). Efficacy was analyzed by IMDC risk factor scores (0, 1, 2, and ≥3) and PD-L1 combined positive score (CPS≥1, <1, or unknown). Data cutoff was February 17, 2025. Results: Among 234 patients in the phase 3 part, IMDC risk scores and PD-L1 CPS distributions are detailed in table. With a median follow-up of 16.56 mo, BIRC-assessed mPFS for F+S vs A/E across IMDC subgroups were: score 0, not estimable(NE) vs 8.31 mo (stratified HR 0.270, p=0.0009); score 1, 24.87 vs 8.25 mo (HR 0.289, p<0.0001); score 2, 13.8 vs 6.9 mo (HR 0.436, p=0.0164); and score ≥3, 9.69 vs 4.21 mo (HR 0.591, p=0.3267). Across PD-L1 expression subgroups, BIRC-assessed mPFS for F+S vs A/E were: CPS ≥1, 22.21 vs 3.22 mo (stratified HR 0.232, p=0.0004); CPS <1, NE vs 8.28 mo (HR 0.350, p<0.0001). An additional 82 patients had unknown PD-L1 CPS status (F+S: n=40; A/E: n=42) and were not included in PD-L1 subgroup analysis. ORR analyses consistently favored F+S over A/E across all subgroups defined by IMDC risk factors and PD-L1 expression, with detailed results presented in table. Conclusions: In the exploratory analyses, these findings suggest that the efficacy benefit of F+S vs A/E is maintained across different IMDC risk scores and PD-L1 CPS in previously treated advanced RCC patients, supporting its broad application. Clinical trial information: NCT05522231 . Efficacy results by IMDC risk scores and PD-L1 expression. F+S v A/E IMDC score 0(33 v 32) IMDC score 1(43 v 41) IMDC score 2(30 v 31) IMDC score ≥3(13 v 11) PD-L1 CPS≥1(23 v 20) PD-L1 CPS<1(56 v 53) mPFS mo NE v 8.31 24.87 v 8.25 13.80 v 6.90 9.69 v 4.21 22.21 v 3.22 NE v 8.28 HR (95%CI) 0.27 (0.12, 0.62) 0.29 (0.15, 0.55) 0.44 (0.22, 0.88) 0.59 (0.20, 1.72) 0.23 (0.10, 0.56) 0.35 (0.20, 0.61) Unstratified Log-rank p 0.0009 < 0.0001 0.0164 0.3267 0.0004 < 0.0001 ORR, % 63.6 v 25.0 62.8 v 26.8 60.0 v 19.4 46.2 v 27.3 78.3 v 10.0 64.3 v 35.8 Odds Ratio (95%CI) 5.25(1.61, 17.71) 4.60(1.66, 12.98) 6.25(1.75, 23.80) 2.29(0.32, 19.10) 32.40(4.67, 338.60) 3.22(1.37, 7.61)

Renal cell carcinoma (RCC), which accounts for 70–90

BackgroundStress hyperglycemia is common in acute ischemic stroke (IS) and has been linked to adverse outcomes. The fasting glucose-to-glycated hemoglobin (HbA1c) ratio (GAR) has been proposed as a simple marker reflecting stress hyperglycemia relative to chronic glycemic status. Still, its prognostic value in patients undergoing endovascular treatment (EVT) remains unclear. This meta-analysis aimed to evaluate the association between GAR and 90d-day functional outcomes in these patients.MethodsPubMed, Embase, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) were systematically searched through May 29, 2025. Studies reporting the association between GAR and poor functional outcome, defined as a modified Rankin Scale (mRS) score of 3–6 at 90 days, were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model accounting for heterogeneity.ResultsTwelve datasets from 10 retrospective cohort studies involving 3,878 patients were analyzed. The pooled analysis showed that a high GAR was significantly associated with an increased risk of poor functional outcome at 90 days after EVT (OR: 2.94, 95% CI: 2.22–3.88, p < 0.001; I2 = 14%). Meta-regression indicated that the proportion of diabetic patients showed a trend toward explaining the observed heterogeneity (coefficient = −0.0088, p = 0.08; I2 residual = 0%), whereas other factors showed no significant influence. Subgroup analyses yielded consistent results across age, sex, diabetes status, National Institutes of Health Stroke Scale (NIHSS), GAR cutoffs, and study quality (p for subgroup difference all > 0.05). The certainty of evidence for the primary outcome was rated as moderate according to the GRADE framework, mainly due to the retrospective design.ConclusionHigh GAR may independently predict poor 90-day functional outcomes after EVT in patients with IS, supporting its potential prognostic value in clinical practice.

Metabolomics has been applied in several studies on cancer, but few studies have screened potential biomarkers for renal cell carcinoma (RCC) by integrating two mass mass spectrometers. This study aims to identify differentially expressed metabolites in plasma samples from patients with RCC compared with healthy individuals, which could be used as potential biomarkers to detect RCC. Plasma samples from 48 patients diagnosed with RCC and 22 healthy individuals were analyzed. Two mass spectrometers were utilized: liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Ceramide m40:0 was significantly less abundant in plasma samples from patients with RCC (P < 0.05), whereas kynureine metabolites and glucose metabolites were significantly more abundant in plasma samples from patients with RCC compared with healthy controls (P < 0.05). A selection of 21 metabolites was utilized to construct an optimal diagnostic model, which achieved an area under the receiver operating characteristic curve (AUC) value of 0.860 (95% confidence interval 0.736-0.960). Significant differences were identified in the metabolic pathways of nicotinate and nicotinamide metabolism, pantothenate and coenzyme A biosynthesis, and beta-alanine metabolism between the RCC group and the control group (P < 0.05). The combined use of LC-MS and GC-MS effectively identified differentially expressed metabolites and dysregulated pathways based on analysis of plasma samples from patients with RCC compared with healthy individuals. The diagnostic model demonstrated robust performance with an AUC of 0.860, highlighting its reliability for RCC identification.

789 Background: A significant proportion of pts with mUC are intolerant to platinum-based chemotherapy, highlighting the urgent need for alternatives. Fexagratinib(former AZD4547)is a potent and selective inhibitor of FGFR and had showed promising anti-tumor activity in mUC pts with FGFRa. This Phase II study (NCT05775874) aimed to evaluate efficacy of Fexa plus T combination treatment (Tx) in mUC pts harboring FGFRa who were 1st-line platinum-ineligible or rejected chemotherapy. Methods: FGFR3 mRNA overexpression were detected by in situ hybridization (RNAscope). FGFR3 activating mutations or fusions were detected by NGS. Eligible pts received continuous oral Fexa 80mg BID plus T 200 mg infusion on day 1 of a 21-day cycle. Primary objectives were objective response rate (ORR) by Independent Review Committee (IRC) per RECIST 1.1. Results: As of data cut off (10 Aug 2024), 26 pts received combination Tx with the majority being treatment-naïve. Of those, 57.7% were male with median age of 68.5 years and 86% had an ECOG of 1. Nine pts had confirmed FGFR3 mutation or fusion and 24 pts were overexpression. In 22 pts with available PD-L1 expression status, 86.4% were negative (CPS<10). Among 24 IRC evaluable pts, 9 (37.5%) partial responses (PRs) were confirmed. The median duration of response was 5.9 months. The median progression free survival mPFS was 5.3 months (95%CI 2.7-8.2) with 4 pts were still on Tx. Among the evaluable pts with FGFR3 overexpression but without mutation/fusion, ORR was37.5%,(6/16)pts.Most common treatment-related adverse events (TRAEs) were stomatitis (42%), anemia (38.5%), AST/ALT increased (27%). Grade ≥3 TRAEs occurred in 12 (46.2%) pts, incidence >10% events included stomatitis (n=3, 12%), hand-foot syndrome(n=3, 12%). Immune-related AEs occurred in 23.0% of pts. The majority of TRAEs were reversible. Conclusions: 1st-line Tx with Fexa plus T were tolerable with a safety profile consistent with previously reported for both agents. The toxicity was overall manageable. Encouraging efficacy was observed in pts with FGFR3 overexpression, regardless of PD-L1 expression or FGFR3 mutations/fusions.Further exploration of these findings is warranted. Clinical trial information: NCT05775874 .

Accurate preoperative glioma grading remains a critical challenge in neuro-oncology. This study presents a novel integrated approach combining deep learning architectures with radiomics features derived from multi-parametric MRI to improve preoperative glioma grading accuracy. In this retrospective multi-center study, we analyzed 847 patients with histopathologically confirmed gliomas from 5 tertiary neurosurgical centers. Multi-parametric MRI sequences (T1, T1-contrast, T2, FLAIR) were processed using a dual-stream framework where: (1) a 3D convolutional neural network extracted deep imaging features, and (2) 1,423 quantitative radiomic features were extracted and selected using a recursive feature elimination algorithm. We developed an ensemble model that integrates both feature streams with clinical variables. Model performance was evaluated through 5-fold cross-validation and external validation on an independent cohort (n = 213). The integrated model achieved superior performance (AUC = 0.946, 95% CI: 0.927-0.965) compared to radiomics-only (AUC = 0.891) or deep learning-only (AUC = 0.903) approaches for distinguishing high-grade (WHO grades III-IV) from low-grade (WHO grades I-II) gliomas. Notably, the model demonstrated robust performance across different MRI acquisition parameters (AUC = 0.921 on external validation). Subgroup analysis revealed particular efficacy in identifying isocitrate dehydrogenase (IDH) wild-type gliomas (sensitivity 0.954, specificity 0.912). The model accurately identified 89.2% of gliomas with molecular features associated with aggressive behavior but ambiguous conventional imaging characteristics. This integrated radiomics-deep learning approach significantly improves preoperative glioma grading accuracy across diverse patient populations and imaging protocols. The proposed framework offers a non-invasive tool for preoperative risk stratification, potentially informing surgical planning and treatment strategies. The model's interpretability provides insights into imaging biomarkers associated with glioma aggressiveness.

Although single-cell analyses have advanced our understanding of pancreatic ductal adenocarcinoma (PDAC), most studies to date have focused on primary and metastatic tumors. Here, we map cell composition, phenotypic plasticity, and microenvironmental remodeling from human normal pancreas through preneoplastic lesions to PDAC, with the preneoplastic phase recognized as a critical window for carcinogenesis. We pinpoint genes that are persistently dysregulated throughout malignant transformation and are associated with a poor prognosis. Focusing on ductal and acinar cells as the principal origins of PDAC, we delineate malignant preneoplastic cell clusters that exhibit strong carcinogenic potential. Immune profiling reveals marked expansion and functional reprogramming of macrophages during disease progression. Integrative analysis with human PDAC bulk transcriptomic cohorts identifies candidate compounds, such as Brefeldin A, with potential for intervention in preneoplastic disease. Together, our study elucidates dynamic molecular and cellular mechanisms underlying PDAC carcinogenesis and provides actionable insights for early intervention and targeted therapy.

This study aims to compare the safety and efficacy of robot-assisted partial nephrectomy (RAPN) and robot-assisted radical prostatectomy (RARP) using the Chinese surgical systems KangDuo-SR-2000 (KD-SR-2000) and EDGE MP1000 (MP1000) versus the Da Vinci Xi (DV-Xi) system, to explore viable alternative options to DV-Xi. This prospective, single-center, non-randomized clinical trial enrolled 261 patients who underwent RAPN or RARP from August 2023 to June 2024. All surgeries were performed by 3 surgeons. For RAPN, the primary outcome included surgical success, positive surgical margin (PSM), warm ischemia time (WIT) and conversion to open or laparoscopic surgery. The secondary outcome was estimated glomerular filtration rate (eGFR). For RARP, the primary outcome was surgical success without conversion to open or laparoscopic surgery, and the secondary outcomes included PSM and urinary continence recovery at 4 weeks post-catheter removal. Baseline demographics were comparable across the KD-SR-2000 group (n = 88), EDGE MP1000 group (n = 59) and DV-Xi group (n = 114). No significant differences observed in primary and secondary outcomes. However, operation time and suture time per stitch were longer in Chinese surgical systems for both RAPN and RARP compared to DV-Xi, and estimated blood loss (EBL) is higher in RAPN. Subgroup analyses indicated that performance differences were primarily attributed to the KD-SR-2000, with no significant differences observed between the MP1000 and DV-Xi. No severe complications (Clavien-Dindo grade ≥ 3) reported in any group. Chinese surgical systems provide a viable alternative, demonstrating non-inferiority compared to DV-Xi. ChiCTR2300074914; Registration Date: 2023-08-21.

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.

BACKGROUND:Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS:A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS:PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

The intratumoral microbiota can modulate the tumor immune microenvironment (TIME); however, the underlying mechanism by which intratumoral microbiota influences the TIME in urothelial carcinoma of the bladder (UCB) remains unclear. To address this, we collected samples from 402 patients with UCB, including paired host transcriptome and tumor microbiome data, from The Cancer Genome Atlas (TCGA). We found that the intratumoral microbiome profiles were significantly correlated with the expression pattern of epithelial-mesenchymal transition (EMT)-related genes. Furthermore, we detected that the genera Lachnoclostridium and Sutterella in tumors could indirectly promote the EMT program by inducing an inflammatory response. Moreover, the inflammatory response induced by these two intratumoral bacteria further enhanced intratumoral immune infiltration, affecting patient survival and response to immunotherapy. In addition, an independent immunotherapy cohort of 348 patients with bladder cancer was used to validate our results. Collectively, our study elucidates the potential mechanism by which the intratumoral microbiota influences the TIME of UCB and provides a new guiding strategy for the targeted therapy of UCB.NEW & NOTEWORTHY The intratumoral microbiota may mediate the bladder tumor inflammatory response, thereby promoting the epithelial-mesenchymal transition program and influencing tumor immune infiltration.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

Abstract Background Atherosclerosis is driven by synergistic interactions between pathological biomechanical and lipid metabolic factors. Long noncoding RNAs (LncRNAs) have been implicated in atherogenesis. The purpose of this study was to investigate the potential mechanism of lncRNA AI662270 on macrophage cholesterol transport in atherosclerosis. Methods Apolipoprotein E deficiency (ApoE −/−) mice were fed a high fat diet for 16 weeks to construct atherosclerotic model, and the mice were injected with recombinant lentivirus carrying AI662270 gene to overexpress AI662270. Macrophages were cleared by liposomal clondronate in vivo. Fundamental experiments and functional assays, hematoxylin and eosin staining, oil red O staining and others, were performed to evaluate the function of AI662270 on atherogenesis. Peritoneal macrophages were treated with oxidized low density lipoprotein (ox-LDL) to simulate in vitro model. Mechanism assays, RNA-interacting protein immunoprecipitation, RNA–protein pulldown and others, were performed to study the regulatory mechanism of AI662270 in macrophages. Results The novel AI662270 was mainly enriched in macrophages, but not in endothelial cells, smooth muscle cells and fibroblasts of mouse atherosclerotic lesions and was upregulated by ox-LDL. Overexpression of AI662270 resulted in lipid accumulation, larger atherosclerotic plaques and cardiac dysfunction in vivo. After macrophages were removed, the pro-atherogenic effect of AI662270 disappeared. Downregulation of AI662270 in macrophages protected against foam cell formation by potentiating cholesterol efflux and reducing intracellular total cholesterol. The opposite effect was observed in macrophage-specific AI662270-overexpressed cells in vitro. AI662270 bound to adenosine triphosphate-binding cassette transporter A1 (Abca1) responsible for regulating cholesterol efflux in macrophages. Forced expression of AI662270 in macrophages decreased Abca1 expression. The reverse occurred when expression of AI662270 was repressed. Conclusion These findings reveal an essential role for AI662270 in atherosclerosis progression by regulating cholesterol efflux from macrophages.

目的:探讨盘龙七片辅助甲氨蝶呤和美洛昔康治疗类风湿关节炎(RA)的疗效及对Toll样受体(TLR)/髓样分化因子88(MyD88)信号通路的影响.方法:选取2018年12月至2021年9月于该院就诊的102例RA患者,按照随机数字表法分为对照组(n=51)和治疗组(n=51).比较两组患者的总有效率,治疗前后的双手平均握力、晨僵时间、28个关节数疾病活动度评分(DAS28)和疼痛数字评价量表(NRS),比较实验室检测指标、TLR2 mRNA、MyD88 mRNA表达水平及不良反应发生情况.结果:治疗组患者的总有效率为94.12％(48/51),高于对照组的80.39％(41/51),差异有统计学意义(P<0.05).与治疗前相比,两组患者治疗后的DAS-28评分、NRS评分显著降低,双手平均握力显著增加,晨僵时间显著缩短,全血低切黏度、全血高切黏度、血浆黏度、纤维蛋白原(FIB)和红细胞沉降率(ESR)均显著降低,类风湿因子(RF)、抗链球菌溶血素O(ASO)、C反应蛋白(CRP)、抗环瓜氨酸肽抗体(ACCP)、TLR2 mRNA和MyD88 mRNA表达水平显著降低,差异均有统计学意义(P<0.05).与对照组相比,治疗组患者治疗后的DAS-28评分、NRS评分降低,双手平均握力增加,FIB、ESR、RF、ASO、CRP、ACCP、TLR2 mRNA和MyD88 mRNA表达水平显著降低,差异均有统计学意义(P<0.05).对照组、治疗组患者的不良反应发生率分别为21.57％(11/51)、23.53％(12/51),差异无统计学意义(P>0.05).结论:盘龙七片辅助甲氨蝶呤和美洛昔康治疗RA患者可有效提高疗效,改善临床症状和体征,减轻疼痛,且安全性高,其可能是通过抑制TLR/MyD88信号通路介导的炎症反应来发挥作用.

液体活检作为肿瘤的无创诊断技术,近年来在前列腺癌的诊疗中取得了突破性进展.但基于实体肿瘤的生物标志物开发面临诸多挑战,特别是晚期前列腺癌常发生骨转移,很难评估骨转移潜在的基因异质性.与传统组织活检相比,液体活检具有取材方便、无创、患者依从性好、可实时监测等优点,可以进行连续检测,能够监测疾病的复发和随着时间推移对治疗的反应,在前列腺癌患者的早期诊断、预后评估和肿瘤监测中将发挥重要作用.

e17040 Background: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the originator abiraterone acetate (ZYTIGA) is observed to be with relatively low bioavailability and high pharmacokinetic variability. Abiraterone Acetate Tablets (I), in which Sodium N-[8-(2-hydroxy-benzoyl) amino] caprylate (SNAC) was added in the formulation as an absorption enhancer, was therefore developed by using nanocrystal technology to enhance the dissolution rate of pharmaceutical compounds, leading to the improvement of the low oral bioavailability and significant food effects. Methods: Patients with mCRPC were randomized (1:1) to receive either Abiraterone Acetate Tablets (I) 300 mg daily plus 5 mg prednisone orally twice daily, or ZYTIGA 1000 mg once daily plus 5 mg prednisone orally twice daily for 84 days. The primary endpoint was serum testosterone concentration (Day 9/10). Secondary endpoints included serum prostate-specific antigen (PSA), pharmacokinetics and adverse events. Results: 68 patients with a median age of 71 (52-84 yrs) (n = 34 in each group) were enrolled in the full analysis set (FAS). The least square geometric mean of Day 9/10 serum testosterone concentration (rounded-up by 1 ng/dl) in Abiraterone Acetate Tablets (I) and ZYTIGA groups was 1.053 (95% CI, 1.006-1.102) and 1.000 (95% CI, 0.956-1.046), respectively. The geometric mean ratio between two groups was 1.053 (90% CI, 0.998-1.110) and the 90% CI fell within 80.0% to 125.0% equivalence limits. The PSA-50 response rate was also similar on Days 28, 56 and 84 (46.9% vs 50.0%, 65.6% vs 57.6%, 71.9% vs 67.7%). Compared with ZYTIGAlabel, no new safety concerns were observed in Abiraterone Acetate Tablets (I). In addition, Abiraterone Acetate Tablets (I) group was observed to be with lower frequency of treatment-emergent adverse events (TEAEs) of any grade (76.5% vs 85.7%), grade ≥3 TEAEs (8.8% vs 22.9%), and grade ≥3 treatment-related adverse events (TRAEs) (5.9% vs 14.3%). Conclusions: Therapeutic equivalence between Abiraterone Acetate Tablets (I) 300 mg and ZYTIGA 1000 mg was confirmed by Day 9/10 serum testosterone concentration in mCRPC patients. Abiraterone Acetate Tablets (I) also showed a trend of improvement in safety profile. Clinical trial information: NCT04862091.