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Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic and invasive nature. Distant metastasis contributes substantially to treatment failure and mortality in NPC. Platelets are versatile blood cells and the number of platelets is positively associated with the distant metastasis of tumor cells. However, the role and underlying mechanism of platelets responsible for the metastasis of NPC cells remain unclear. Here we found that the distant metastasis of NPC patients was positively correlated with the expression levels of integrin β3 (ITGB3) in platelet-derived extracellular vesicles (EVs) from NPC patients (P-EVs). We further revealed that EVs transfer occurred from platelets to NPC cells, mediating cell-cell communication and inducing the metastasis of NPC cells by upregulating ITGB3 expression. Mechanistically, P-EVs-upregulated ITGB3 increased SLC7A11 expression by enhancing protein stability and activating the MAPK/ERK/ATF4/Nrf2 axis, which suppressed ferroptosis, thereby facilitating the metastasis of NPC cells. NPC xenografts in mouse models further confirmed that P-EVs inhibited the ferroptosis of circulating NPC cells and promoted the distant metastasis of NPC cells. Thus, these findings elucidate a novel role of platelet-derived EVs in NPC metastasis, which not only improves our understanding of platelet-mediated tumor distant metastasis, but also has important implications in diagnosis and treatment of NPC.

Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge. We report a versatile, label-free quantification proteomics platform for competitive profiling of cysteine-reactive fragments against the native proteome. This high-throughput platform combines SP4 plate-based sample preparation with rapid chromatographic gradients. Data-independent acquisition performed on a Bruker timsTOF Pro 2 consistently identified ~23,000 cysteine sites per run, with a total of ~32,000 cysteine sites profiled in HEK293T and Jurkat lysate. Crucially, this depth in cysteinome coverage is met with high data completeness, enabling robust identification of liganded proteins. In this study, 80 reactive fragments were screened in two cell lines identifying >400 ligand-protein interactions. Hits were validated through concentration-response experiments and the platform was utilised for hit expansion and live cell experiments. This label-free platform represents a significant step forward in high-throughput proteomics to evaluate ligandability of cysteines across the human proteome. This paper presents a label-free chemoproteomics platform using data-independent acquisition to profile covalent fragment binding across the human proteome. The platform offers high reproducibility and data completeness, identifying >400 protein-ligand interactions for probe development.

Importance Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited. Objectives To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis. Design, Setting, and Participants This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021. Exposures Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications. Main Outcomes and Measures The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)–related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression. Results Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR], 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure]: HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use]: HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31]; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33]) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52]; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth factor 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16]), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78]; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26]; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79]) had higher odds of CAC progression compared with patients who achieved all 3 target levels. Conclusions and Relevance In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease–mineral and bone disorder among patients undergoing dialysis.

Background Previous studies provided inconsistent results on the effects of antioxidant intake on lung cancer prevention. This study aimed to investigate the association between the composite dietary antioxidant index (CDAI), which calculated the dietary intake of manganese, selenium, zinc, vitamins A, C and E, and the risk of lung cancer. Methods Using prospective data from the UK Biobank, this study employed Cox proportional hazards regression models to evaluate the relationship between CDAI and lung cancer risk, and restricted cubic spline analyses were used to explore potential nonlinear associations. Multiplicative and additive interaction analyses were conducted to assess the joint effects of CDAI and smoking status on lung cancer risk. Results Among 201,316 participants over a median follow-up of 11.8 years, 1,229 new cases of lung cancer were identified. Multivariate analysis showed that participants in the highest quartile of CDAI had a significantly lower risk of lung cancer (HR: 0.70; 95% CI: 0.57–0.86; P  < 0.001), compared with those in the lowest quartile. An interaction effect between CDAI and smoking status was noted ( P  = 0.001). Among former smokers, the hazard ratio was 4.58 (95% CI: 3.36–6.25; P  = 8.42 × 10⁻ 22 ) in the lowest CDAI quartile and decreased to 2.60 (95% CI: 1.83–3.70; P  = 1.10 × 10⁻⁷) in the highest quartile, compared to never smokers in the lowest CDAI quartile. Conclusion This study revealed a significant link between increased dietary antioxidant intake and a reduced risk of lung cancer, particularly in former smokers.

Background To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children’s CHD after thoracotomy. Methods This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. Results A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3, P  < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3, P  < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P  < 0.05). Conclusions The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.

Background Depression is are often insufficiently managed in cancer patients globally. To address this, we conducted a comprehensive systematic review and network meta-analysis to evaluate and compare the effectiveness of pharmacological and non-pharmacological interventions in alleviating depressive symptoms in adult cancer patients. Methods We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception until 31 July 2024, with an updated search conducted on 10 January 2025. Eligible studies were randomised controlled trials evaluating pharmacological or non-pharmacological interventions for depressive symptoms in adult patients with cancer (aged ≥18 years). Studies involving paediatric populations, lacking complete outcome data, or not reporting intervention outcomes were excluded. A Bayesian network meta-analysis was undertaken to compare the effectiveness of included interventions. The review protocol was prospectively registered in PROSPERO (CRD42023465056). Findings A total of 95 RCTs involving 17,260 participants were included. Several non-pharmacological interventions indicated potential benefit compared with usual care, notably massage and touch therapy (standardised mean difference [SMD]: −0.76, 95% CI: −1.37 to −0.16; low certainty), relaxation therapy (SMD: −0.59, 95% CI: −1.06 to −0.11; low certainty), psychotherapy (SMD: −0.43, 95% CI: −0.56 to −0.30; low certainty), and education and support of person with cancer (SMD: −0.30, 95% CI: −0.45 to −0.14; low certainty). Among pharmacological approaches, preliminary findings suggest the combination of mirtazapine and methylphenidate may offer benefits compared with placebo (SMD: −2.46, 95% CI: −4.24 to −0.70; low certainty). However, the overall evidence quality was low, reflecting substantial variability and limited data. Interpretation Non-pharmacological interventions such as massage, relaxation therapies, and psychotherapy show promise in alleviating depressive symptoms in cancer patients. Limited preliminary evidence also suggests possible benefits of combined pharmacological treatment (mirtazapine plus methylphenidate). More rigorous research is required to strengthen these findings and better inform clinical practice.

ObjectivesTo assess the readability of printed education materials (PEMs) for patients with systemic lupus erythematosus (SLE) and to explore the perceptions of patients with SLE with different health literacy regarding the readability of PEMs.DesignA mixed-methods study, including a cross-sectional survey and semistructured interviews.SettingThe SLE PEMs were collected from 13 hospitals in China. The interviews were conducted in the Department of Rheumatology of a hospital in Hefei, China.ParticipantsIn the cross-sectional survey, convenience sampling was used to select the Chinese SLE PEMs, with 20 PEMs included. In the qualitative study, the patients with SLE were divided into two groups based on their health literacy. Then, purposive sampling was used to select participants in each group, with 18 patients recruited.Outcome measuresThe readability of PEMs was assessed by the language analysis technology and the Chinese version of the Suitability Assessment of Materials (SAM-C) instrument.ResultsFor text factors of readability, the mean Chinese language difficulty coefficient was 67.09±8.03, which indicates that the text of PEMs was difficult to read. For non-text factors, the mean SAM-C score was 45.62±9.51. Eight PEMs were rated not suitable, 12 were adequate and none were superior. In the interviews, eight categories were identified: information source, content, actionability, plain language, pictures, tables, numbers and layout. Patients with different health literacy had discrepant views on the detail of basic information, the necessity of question list, the location of functional pictures and the application of mathematical symbols.ConclusionsThe readability of Chinese SLE PEMs does not perform well, and it is necessary to reduce the difficulty of words, shorten the length of sentences and improve the picture design and actionability. To develop PEMs tailored to patients’ level of health literacy, patients’ unique view of readability should be integrated into the design of PEMs.

Acute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia characterized by unrestricted megakaryoblast proliferation and poor prognosis. Thrombopoietin receptor c-Mpl is a primary regulator of megakaryopoeisis and a potent mitogenic receptor. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however, the role of c-Mpl in AMKL progression remains largely unexplored. Here, we identified increased expression of a c-Mpl alternative splicing isoform, c-Mpl-del, in AMKL patients. We found that c-Mpl-del expression was associated with enhanced AMKL cell proliferation and chemoresistance, and decreased survival in xenografted mice, while c-Mpl-del knockdown attenuated proliferation and restored apoptosis. Interestingly, we observed that c-Mpl-del exhibits preferential utilization of phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in upregulation of GATA1 and downregulation of DDIT3-related apoptotic responses conducive to AMKL chemoresistance and proliferation. Thus, this study elucidates the critical roles of c-Mpl alternative splicing in AMKL progression and drug resistance, which may have important diagnostic and therapeutic implications for leukemia accelerated by c-Mpl-del overexpression.

Objectives To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). Methods The clinical data of children with CHD aged 0–14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. Results A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0–14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. Conclusions The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.

Abstract Background Nasopharyngeal carcinoma (NPC) is characterized by pronounced metastatic and invasive properties. Emerging research has elucidated that circular RNAs (circRNAs) are intricately associated with the pathogenesis of NPC, potentially serving as critical mechanisms in tumorigenesis and as promising therapeutic targets for NPC. Methods The expression levels of circRNAs were analyzed in NPC using reverse transcription quantitative PCR (RT-qPCR). Wound healing, transwell, and clone formation assays were conducted to examine the metastatic potential of NPC. Cell proliferation and apoptosis assays were performed to evaluate cell proliferation and survival. 3D spheroid cultures, RNA pull-down, LC-MS, RNA-sequencing, and luciferase reporter assays were carried out to examine the mechanisms of circPPP1CB in NPC progression. NPC xenograft tumor models were estimated to verify the mechanisms of circPPP1CB in tumor growth and metastasis of NPC in vivo. Results CircPPP1CB subtype, hsa_(c)irc₀007439, that was more highly expressed in NPC patients with distant metastasis than in those without distant metastasis. Hsa_(c)irc₀007439 overexpression specifically promotes proliferation and inhibits the apoptosis of NPC cells. Further experiments indicated that hsa_(c)irc₀007439 overexpression was correlated with increased tumor growth and distant metastasis of NPC cells. Mechanistically, hsa_(c)irc₀007439 upregulated KRT1 expression by acting as a sponge for miR-1275 and miR-1293. This led to increased proliferation and metastatic progression in NPC by activating the JAK/STATs signaling pathway. Conclusions This study is the first to demonstrate that hsa_(c)irc₀007439 functions as a competitive endogenous RNA to upregulate KRT1 expression, thereby promoting the metastasis of NPC, suggesting that hsa_(c)irc₀007439 serve as a potential diagnostic biomarker and therapeutic target for NPC.