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Both epithelial-mesenchymal transition (EMT) and immune regulation are important biological process in malignant tumours. The current research aims to comprehensively explore the potential association between the epithelial-mesenchymal transition (EMT) signature and immune checkpoint signature and its role in predicting the prognosis of clear-cell renal cell carcinoma (ccRCC) patients. EMT-related genes were collected from an experiment-based study and then were investigated using data from the Cancer Genome Atlas. A total of 357 genes were included, and 23 of them that were upregulated and correlated with prognosis were analysed further as core EMT genes in ccRCC. Interestingly, the emerging immune checkpoints CD276, OX40 and TGFB1 were found to be significantly co-expressed with core EMT genes, and TGFB1, CXCR4, IL10, and IL6 were the most important molecules potentially interacting with EMT molecules in our model, as determined from mRNA co-expression and protein-protein interaction network analysis. Additionally, an integrated scoring model based on FOXM1, TIMP1 and IL6 was successfully established to distinguish ccRCC patients with different clinical risks. Our results identified core genes in the EMT-immunophenotyping correlation and evaluated their risk assessment capabilities, providing more potential therapeutic targets and prediction approaches regarding the translational research of treatment and prognosis in ccRCC.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis ( p -value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4 + T cell, CD8 + T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8 + T cells, resting memory CD4 + T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

Background Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer. Methods We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed. Results A total of 329 patients were included. The median duration of follow-up was 54.8 months. Patients with an early post-operative serum albumin level < 32 g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5 months, P  = 0.001) and median overall survival (OS; 52.2 versus 57.0 months, P  = 0.049) than patients with an early post-operative serum albumin level ≥ 32 g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level < 32 g/L was an independent prognostic factor associated with a decreased RFS (HR = 3.60; 95% CI,1.05–12.42 [months], P  = 0.042) and decreased OS (HR = 9.95; 95% CI, 1.81–54.80 [months], P  = 0.008). Conclusion An early post-operative serum albumin level < 32 g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.

PurposeDeveloping a risk prediction model for invasive fungal disease based on an analysis of the disease-related risk factors in critically ill patients in the intensive care unit (ICU) to diagnose the invasive fungal disease in the early stages and determine the time of initiating early antifungal treatment.MethodsData were collected retrospectively from 141 critically ill adult patients with at least 4 days of general ICU stay at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from February 2015 to February 2016. Logistic regression was used to develop the risk prediction model. Discriminative power was evaluated by the area under the receiver operating characteristics (ROC) curve (AUC).ResultsSequential organ failure assessment (SOFA) score, antibiotic treatment period, and positive culture of Candida albicans other than normally sterile sites are the three predictors of invasive fungal disease in critically ill patients in the ICU. The model performs well with an ROC-AUC of .73.ConclusionThe risk prediction model performs well to discriminate between critically ill patients with or without invasive fungal disease. Physicians could use this prediction model for early diagnosis of invasive fungal disease and determination of the time to start early antifungal treatment of critically ill patients in the ICU.

Toll-like receptor 4 (TLR4) has an important role in the recognition of lipopolysaccharide (LPS) and in the activation of the inflammatory cascade. In the present study, the effect of TLR4 monoclonal antibody (mAb) on LPS-induced acute lung injury (ALI) was investigated in mice. A total of 45 male BALB/c mice were randomly divided into three groups, namely, the control (group C), sepsis (group S) and pretreatment groups (group P). Mice in group P were intraperitoneally treated with TLR4 mAb 1 h prior to the intraperitoneal administration of LPS. Following treatment with LPS for increasing times periods in groups S and P, the mRNA expression level of TLR4 in the lung tissue and the expression of inflammatory factors in the serum were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. The degree of pulmonary edema, expressed as (wet weight - dry weight)/wet weight, as well as the lung injury scores, observed using a light microscope, were also analyzed. The results demonstrated that intraperitoneal administration of LPS in mice increased the mRNA expression levels of TLR4, the secretion of inflammatory factors in the serum, the degree of pulmonary edema and the lung injury score in a time-dependent manner. However, pretreatment with TLR4 mAb effectively attenuated the increased mRNA expression of TLR4 and the overproduction of inflammatory factors to correct the pulmonary edema and the elevated lung injury score induced by LPS. Therefore, TLR4 plays a critical role in LPS-induced ALI, and the TLR4 mAb decreases the secretion of inflammatory factors and attenuates the degree of pulmonary edema, thereby protecting the lungs from LPS-induced ALI.

Background. The adjuvant use of mitotane on adrenocortical carcinoma (ACC) has always been in controversy. We aimed to assess the prognostic benefits of adjuvant mitotane after resection of ACC in patients without distant metastasis. Methods. The PubMed, WoS, Embase, and Cochrane Library databases were systematically searched. Recurrence-free survival (RFS) and overall survival (OS) were adopted as measurements. A meta-analysis was conducted based on hazard ratio (HR) with 95% confidence interval (CI). A study was included only if the enrolled patients underwent resection of ACC without adjuvant chemotherapy except mitotane. Results. A total of 5 retrospective studies reporting on 1249 patients were included for this meta-analysis. The meta-analysis showed that adjuvant mitotane was significantly associated with prolonged RFS (HR = 0.62; 95%CI, 0.42-0.94; P < 0.05) and prolonged OS (HR = 0.69; 95%CI, 0.55-0.88, P < 0.05). Conclusion. After comprehensive review, current evidence suggests that adjuvant mitotane significantly decreases the recurrence rate and mortality after resection of ACC in patients without distant metastasis, but these findings need further demonstration from prospective controlled trials.

AbstractObjectiveTo evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.DesignMulticentre, double blinded, placebo controlled phase 3 trial.Setting22 centres in China, September 2016 to December 2020.Participants1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre.InterventionsSubcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent.Main outcome measureThe primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug.ResultsOf 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.97, 95% confidence interval 0.76 to 1.24; P=0.82 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04).ConclusionsThis trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis.Trial registrationClinicalTrials.gov NCT02867267.

Darolutamide, a novel androgen receptor inhibitor, significantly improved outcomes in the ARASENS trial when combined with androgen deprivation therapy (ADT) and docetaxel chemotherapy for metastatic hormone-sensitive prostate cancer (mHSPC). In China, the regimen has been reimbursed since December 2023, expanding real-world accessibility. PSMA imaging-guided focal therapy enables precise localization of residual or oligometastatic lesions and may complement systemic control. To evaluate the real-world efficacy and safety of darolutamide-based triplet therapy combined with PSMA imaging-guided focal treatment in patients with mHSPC. This multicenter, retrospective study included 17 patients treated across three tertiary hospitals between June 2023 and June 2024. All patients received darolutamide (600 mg twice daily), ADT, and docetaxel (75 mg/m every 3 weeks for 4-6 cycles), followed 4-6 weeks later by focal therapy (surgery or radiotherapy) based on multidisciplinary team (MDT) assessment and PSMA IMAGING findings. Data collection followed STROBE recommendations. The primary endpoint was PSA90 response; secondary endpoints included PSA ≤0.2 ng/mL, PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and safety. Seventeen patients with predominantly low- to intermediate-volume metastatic disease were analyzed. The PSA90 response rate was 94.1%, and 82.4% achieved PSA ≤0.2 ng/mL. Median PSA-PFS and rPFS were not reached at a median follow-up of 16 months. The 12-/18-month PSA-PFS rates were 88% and 65%, while the corresponding rPFS rates were 94% and 76%. Grade 1-2 myelosuppression (64.7%) and fatigue (47.1%) were most common; grade 3 neutropenia occurred in two patients (11.8%) without grade ≥4 events. Focal therapy was well tolerated, with no severe complications. Darolutamide-based triplet therapy combined with PSMA-guided focal intervention achieved deep biochemical responses and durable disease control with manageable toxicity in real-world Chinese patients with mHSPC. The multicenter design and standardized methodology support the feasibility of this multimodal approach, which warrants validation in larger prospective studies.

Ribosomal protein S15A (RPS15A), a member of the ribosomal protein gene family, was demonstrated to be closely associated with tumorigenesis in multiple human malignancies. Nevertheless, the role of RPS15A in the progression of renal cell carcinoma (RCC) remains unknown. In the present study, by comparing the publicly available data from RCC tissues and reverse transcription-quantitative polymerase chain reaction results, it was identified that RPS15A was upregulated in RCC tissues and cell lines (P<0.001). Notably, knockdown of RPS15A suppressed 786-O cell proliferation (P<0.001) and promoted its apoptosis/necrotic (P=0.0001) in vitro. Additionally, tumour formation and growth of transfected 786-O cells were observed to be restrained in a mouse model (P<0.05). Subsequent to analysing the microarray data, 747 genes were differentially expressed in the RPS15A-knockdown 786-O cells. The enriched canonical pathways, diseases and functions of differentially expressed genes, and the interactive network of RPS15A in RCC were successfully constructed by ingenuity pathway analysis. Overall, the present results provided a preliminary experimental basis for RPS15A as a novel oncogene and potential therapeutic target in RCC.

Background As COVID-19 continues to spread globally, traditional emergency management measures are facing many practical limitations. The application of big data analysis technology provides an opportunity for local governments to conduct the COVID-19 epidemic emergency management more scientifically. The present study, based on emergency management lifecycle theory, includes a comprehensive analysis of the application framework of China’s SARS epidemic emergency management lacked the support of big data technology in 2003. In contrast, this study first proposes a more agile and efficient application framework, supported by big data technology, for the COVID-19 epidemic emergency management and then analyses the differences between the two frameworks. Methods This study takes Hainan Province, China as its case study by using a file content analysis and semistructured interviews to systematically comprehend the strategy and mechanism of Hainan’s application of big data technology in its COVID-19 epidemic emergency management. Results Hainan Province adopted big data technology during the four stages, i.e., migration, preparedness, response, and recovery, of its COVID-19 epidemic emergency management. Hainan Province developed advanced big data management mechanisms and technologies for practical epidemic emergency management, thereby verifying the feasibility and value of the big data technology application framework we propose. Conclusions This study provides empirical evidence for certain aspects of the theory, mechanism, and technology for local governments in different countries and regions to apply, in a precise, agile, and evidence-based manner, big data technology in their formulations of comprehensive COVID-19 epidemic emergency management strategies.